AT FRANKLIN Plaintiffs, Defendants. - Tennessee Stands

IN THE CHANCERY COURT FOR WILLIAMSON COUNTY, TENNESSEE AT FRANKLIN

CITIZENS FOR LIMITED ) GOVERNMENT AND ) CONSITUTIONAL INTEGRITY, INC., ) d/b/a TENNESSEE ST ANDS, et al., )

Plaintiffs, v.

ROGERS C. ANDERSON, in his official capacity as Mayor of Williamson County, Tennessee, and WILLIAMSON COUNTY, TENNESSEE,

Defendants.

) ) ) ) ) ) ) ) ) ) )

Case No. 20CV-49908B Judge Binkley

APPENDIX TO JAMES R. CASCIANO'S DECLARATION OF SCIENTIFIC STUDIES and ARTICLES

APPENDIX TO JAMES R. CASCIANO DECLARATION- 1

TABLE OF CONTENTS

Document Page

Scientific Brief: Community Use of Cloth Masks to Control the Spread ofSARS-CoV-2, Center for Disease Control and Prevention (November 20, 2020) ................................................................................... 5

Mask Facts, Association of American Physicians and Surgeon (September 26, 2020) ............................................................................................................ 15

Mask Use In The Context Of COVID-19, World Health Organization (December 1, 2020) ................................................................. .48

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-Co V-2 Infection in Danish Mask Wearers: A randomized Controlled Trial, ANNALS OF INTERNAL MEDICINE (November 18, 2020) ............................................. 70

Reduction Of Secondary Transmission Of SARS-Cov-2 In Households By Face Mask Use, Disinfection And Social Distancing: A Cohort Study In Beijing, China, BRITISH JOURNAL OF MEDICINE {May 28, 2020) ................................................................... 73

Case-Control Study of Use of Personal Protective Measure and Risk/or SARS-CoV-2 Infection, Thailand, Center for Disease Control and Prevention (November 2020) .............................................. 85

Physical Interventions To Interrupt Or Reduce The Spread Of Respiratory Viruses, Institute For Evidence-Based Healthcare, Bond University (November 20, 2020) ................................................................................. 98

Nonpharmaceutica/ Measures for Pandemic Influenza in Nonhea/thcare Settings - Personal Protective and Environmental Measures, Centers for Disease Control and Prevention (May 2020) ...................................................... 103

A Cluster Randomized Trial Of Cloth Masks Compared With Medical Masks In Healthcare Workers, British Journal Open, (April 2015) ........................................................................................ 110


Household Transmission of SARS-Co V-2, JOURNAL OF AMERICAN MEDICAL ASSOCIATION (December 14, 2020) ............................................................................................................. 128

Post-Lockdown SARS-Cov2 Nucleic Acid Screening In Nearly Ten Million Residents Of Wuhan, China, Nature Communications (November 20, 2020) .................................................................... 160

Guidance on Preparing Workplaces for COVJD-19 U.S. Occupational Safety and Health Administration .......................................................... 186

Rational Use Of Face Masks In The COVJD-19 Pandemic, UK MEDICAL JOURNAL LANCET (March 20, 2020) ............................................................... 221

Double Dutch Face Masks Are 'NOT Necessary' And Could Even Harm The Fight Against Coronavirus, Say Holland's Top Scientists, The Sun (August 2, 2020) ..................................................... 227

Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness THE JOURNAL OF INFECTIOUS DISEASE (October 2008) ......................................................... 234

When Mask-Wearing Rules in the 1919 Pandemic Faced Resistance, Becky Little (May 6, 2020) ..................................................................... 312

Do Facemasks Limit the Contamination/Spread of Respiratory Viruses? Admin-Spiralab, University of Sao Paulo, Bacterial Genetics Lab (July 27, 2020) ......................................... 319

Rapid Expert Consultation on the Effectiveness of Fabric Masks for the COVID-19 Pandemic, The National Academies of Sciences Engineering Medicine, April 8, 2020) ....................... 326

A Quantitative Assessment of the Total Inward Leakage of NaCl Aerosol Representing Submicron-Size Bioaerosol Through N95Filtering Facepiece Respirators and Surgical Masks, JOURNALOFOCCUPATIONALANDENVIRONMENTALHYGIENE (May 9, 2014) ...................... 342

Mask Use In The Context Of COVID-19, World Health Organization (December 1, 2020) .................................................................. 364

The Psychological Impact Of The COVID-19 Epidemic On College Students


In China, PSYCHIATRY RESEARCH (2020) ............................................................................ 22

Coronavirus Having Major Impact On Young People With Mental Health Needs -New Survey, YoungMinds, March 30, 2020 ...................................................................... 23

APPENDIX TO JAMES R. CASCIANO DECLARATION-4

Scientific Brief: Community Use of Cloth Masks to Control the Spread of SARS-CoV-2 Background

SARS-CoV-2 infection is transmitted predominately by respiratory droplets

generated when people cough, sneeze, sing, talk, or breathe. CDC

recommends community use of masks, specifically non-valved multi-layer

cloth masks, to prevent transmission of SARS-CoV-2. Masks are primarily

intended to reduce the emission of virus-laden droplets ("source control"),

which is especially relevant for asymptomatic or presymptomatic infected

wearers who feel well and may be unaware of their infectiousness to others,

and who are estimated to account for more than 50% of transmissions. 1,2

Masks also help reduce inhalation of these droplets by the wearer

("filtration for personal protection"). The community benefit of masking for

SARS-CoV-2 control is due to the combination of these effects; individual

prevention benefit increases with increasing numbers of people using

masks consistently and correctly.

Source Control to Block Exhaled Virus

Multi-layer cloth masks block release of exhaled respiratory particles into

the environment, 3-6 along with the microorganisms these particles carry.7•8

Cloth masks not only effectively block most large droplets (i.e., 20-30

microns and larger)9 but they can also block the exhalation of fine droplets

and particles (also often referred to as aerosols) smaller than 10 microns

;3,5 which increase in number with the volume of speech 10-12 and specific

types of phonation. 13 Multi-layer cloth masks can both block up to 50-70%

of these fine droplets and particles 3,14 and limit the forward spread of those

that are not captured. 5,6,15,16 Upwards of 80% blockage has been achieved

APPENDIX TO JAMES CASCIANO DECLARATION-5

in human experiments that have measured blocking of all respiratory

droplets, 4 with cloth masks in some studies performing on par with surgical

masks as barriers for source control. 3,9,14

Filtration for Personal Protection

Studies demonstrate that cloth mask materials can also reduce wearers'

exposure to infectious droplets through filtration, including filtration of fine

droplets and particles less than 10 microns. The relative filtration

effectiveness of various masks has varied widely across studies, in large

part due to variation in experimental design and particle sizes analyzed.

Multiple layers of cloth with higher thread counts have demonstrated

superior performance compared to single layers of cloth with lower thread

counts, in some cases filtering nearly 50% of fine particles less than 1

micron .14,17-29 Some materials (e.g., polypropylene) may enhance filtering

effectiveness by generating triboelectric charge {a form of static electricity)

that enhances capture of charged particles 18,30 while others (e.g., silk) may

help repel moist droplets 31 and reduce fabric wetting and thus maintain

breathability and comfort.

Human Studies of Masking and SARS-CoV-2 Transmission

Data regarding the "real-world" effectiveness of community masking are

limited to observational and epidemiological studies.

An investigation of a high-exposure event, in which 2 symptomatically ill hair stylists interacted for an average of 15 minutes with each of 139 clients

during an 8-day period, found that none of the 67 clients who subsequently

consented to an interview and testing developed infection. The stylists and

all clients universally wore masks in the salon as required by local ordinance

and company policy at the time.32

In a study of 124 Beijing households with> 1 laboratory-confirmed case of


SARS-CoV-2 infection, mask use by the index patient and family contacts

before the index patient developed symptoms reduced secondary

transmission within the households by 79%.33

A retrospective case-control study from Thailand documented that, among

more than 1,000 persons interviewed as part of contact tracing

investigations, those who reported having always worn a mask during high

risk exposures experienced a greater than 70% reduced risk of acquiring

infection compared with persons who did not wear masks under these

circumstances. 34

A study of an outbreak aboard the USS Theodore Roosevelt, an

environment notable for congregate living quarters and close working

environments, found that use of face coverings on-board was associated

with a 70% reduced risk. 35

Investigations involving infected passengers aboard flights longer than 10

hours strongly suggest that masking prevented in-flight transmissions, as

demonstrated by the absence of infection developing in other passengers

and crew in the 14 days following exposure.36,37

Seven studies have confirmed the benefit of universal masking in

community level analyses: in a unified hospital system,38 a German city,39 a

U.S. state,40 a panel of 15 U.S. states and Washington, D.C.,41,42 as well as

both Canada43 and the U.S.44 nationally. Each analysis demonstrated that,

following directives from organizational and political leadership for universal

masking, new infections fell significantly. Two of these studies 42,44 and an

additional analysis of data from 200 countries that included the U.S.45 also

demonstrated reductions in mortality. An economic analysis using U.S. data

found that, given these effects, increasing universal masking by 15% could

prevent the need for lockdowns and reduce associated losses of up to $1

trillion or about 5% of gross domestic product. 42

Conclusions

Experimental and epidemiological data support community masking to


reduce the spread of SARS-CoV-2. The prevention benefit of masking is

derived from the combination of source control and personal protection for

the mask wearer. The relationship between source control and personal

protection is likely complementary and possibly synergistic 14, so that

individual benefit increases with increasing community mask use. Further

research is needed to expand the evidence base for the protective effect of

cloth masks and in particular to identify the combinations of materials that

maximize both their blocking and filtering effectiveness, as well as fit,

comfort, durability, and consumer appeal. Adopting universal masking

policies can help avert future lockdowns, especially if combined with other

non-pharmaceutical interventions such as social distancing, hand hygiene,

and adequate ventilation.

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tract.


Mask Facts

curated by Marilyn M. Singleton, M.D., J.D. -

httQ://.marilynsingletonmdjd.com/.

Updated September 26, 2020

Introduction

COVID-19 is as politically-charged as it is infectious. Early in the COVID-19

pandemic, the WHO, the CDC and NIH's Dr. Anthony Fauci discouraged

wearing masks as not useful for non-health care workers. Now they

recommend wearing cloth face coverings in public settings where other

social distancing measures are hard to do (e.g., grocery stores and

pharmacies). The recommendation was published without a single scientific

paper or other information provided to support that cloth masks actually

provide any respiratory protection. Let's look at the data.

The theory behind mask wearing:


• Source control: Cloth mask can trap droplets that come out of a

person's mouth when they cough or sneeze.

• Protection: Personal Protective Equipment (PPE) - only N95 masks

Transmission of SARS-CoV-2

Note: A COVID-19 (SARS-CoV-2) particle is 0.125 micrometers/microns

(µm); influenza virus size is 0.08 - 0.12 µm; a human hair is about 150 µm.

*1 nm = 0.001 micron; 1000 nm = 1 micron; Micrometer (µm) is the

preferred name for micron

*1 meter is = 1,000,000,000 [trillion] nm or 1,000,000 [million] microns

*For a complete dissection and explanation of aerosols and airborne

particles, please see Understanding Particle Size and Aerosol-based

Transmission by Steve Probst. httgs:Uwww.4cconference.comLwg

content/ugloadsL2020L07 LUnderstanding-Particle-Size-and-Aerosol

Based-Transmission.gdf

Droplets

• Virus is transmitted through respiratory droplets produced when an

infected person coughs, sneezes, or talks.

o Larger respiratory droplets (>5 µm) remain in the air for only a

short time and travel only short distances, generally <1 meter.

They fall to the ground

q u ickly.h tt,Qs:/Lwww. the la nee t. com/j_ou rna I s/ja n re sLa rticle/PII S2 213

-2600(.20130245-9jfulltext

o This idea guides the CDC's advice to maintain at least a 6-foot

distance.

• Small ( <5 µm) aerosolized droplets can remain in the air for at least 3

hours and travel long distances (up to 27 ft.). 0 b1t~/Lwww.nejm.org/doiJpdfL10.1056/_NEJMc2004973?


articleTools=true:

o httgs:f/.www.cid rag.um n .ed u/.covid-19 /.god casts-we bi na rs/.sgecia l

eg-masks;

o httgs:f/.www. na g.ed u/.cata log/.2 5769/.ragid-exgert-consu ltation

o n-th e-goss i bi I itY.-of-bi oa e ro so I-s g read-of- sa rs-cov- 2-for -the

cov i d-19- ga n demi c-a g ril-1-2020

Air currents

• In an air conditioned environment these large droplets may travel farther.

• Ventilation. Even the opening of an entrance door and a small window can dilute the number of small droplets to one half after 30 seconds. (This study looked at droplets from uninfected persons). This is clinically relevant because poorly ventilated and populated spaces, like public transport and nursing homes, have high SARS-CoV-2 disease transmission despite physical distancing.

o httQ.s:/Lwww.thelancet.com/j_ourna/s/janresLarticleLPIIS2213-

2600(.20) 30245-9Lfulltext

Humidity

• Since 1961, experiments showed that viral-pathogen-carrying droplets were inactivated within shorter and shorter times as ambient humidity was increased. Dryness drives the small aerosol particles. See e.g., review of studies, httQ.s:/Laagr.orgLarticlesLaagr-20-06-covid-0302

Conclusions

The preponderance of scientific evidence supports that aerosols play a critical role in the transmission of SARS-CoV-2. Years of dose response studies indicate that if anything gets through, you will become infected.

• Thus, any respiratory protection respirator or mask must provide a high


level of filtration and fit to be highly effective in preventing the

transmission of SARS-CoV-2. (Works for Mycobacterium tuberculosis

(3µm)

• Public health authorities define a significant exposure to COVID-19 as

face-to-face contact within 6 feet with a patient with symptomatic

COVID-19 that is sustained for at least a few minutes (and some say

more than 10 minutes or even 30 minutes).

o The chance of catching COVID-19 from a passing interaction in a

public space is therefore minimal.

MASKS

filter EfficieocY-and fit

Data from a University_ of Illinois at Chicago review httQ.s./Lwww. cidraQ.. umn. eduLnews-P-,ersP-,ectiveL2020L04Lcommentant_

masks-al/-covid-19-not-based-sound-data

• HEPA (high efficiency particulate air) filters are 99.97 to 100% efficient.

HEPA filters are tested with particles that are 0.125 µm (the size of

SARS-CoV-2).

• Masks and respirators work by collecting particles through several

physical mechanisms, including diffusion (small particles) and

interception and impaction (large particles).

• Surgical masks are loose-fitting devices that were designed to be worn

by medical personnel to protect accidental contamination of patient

wounds, and to protect the wearer against splashes or sprays of bodily

fluids. They aren't effective at blocking particles smaller than 100 µm.

httP-,s:/Lmultimedia.3m.comLmwsLmediaL957730O/.resP-,irators-andsurgica/-masks-contrast-technica/-bulletin.Q.df

o OSHA/CDC: A surgical mask is not a respirator. It cannot be used

to protect workers who perform or assist with aerosol-generating

procedures, which may create very fine aerosol sprays. A surgical


mask can only be used to protect workers from contact with the large droplets made by patients when they cough, sneeze, talk or breathe. httQ.s://_www.osha.gov/_dtsjguidance/_f/u/_healthcare. html

Laboratory Studies

• N95 filtering facepiece respirators (FFRs) are constructed from electret

(a dielectric material that has a quasi-permanent electric charge.) An

electret generates internal and external electric fields so the filter

material has electrostatic attraction for additional collection of all

particle sizes. As flow increases, particles will be collected less

efficiently.

• A JJmJJJUlY.. fitted N95 will block 95% of tiny air particles down to

0.3 µm from reaching the wearer's face.

o httQ.s://_www.honev_we/1.com/_en-us/_newsroom/_ne ws/_2020/_03/_n95-

masks-ex,:J./ained.

o Problem: no source control. An N95 does not filter exhaled air

passing through the exhaust/exhalation valve (for easier breathing

and less moisture inside the mask).

• Study measuring filter efficiency (2010)

o httQ.s.//_academic. OUQ.. com/_annweh/_artic/e/_54/_7 /_789/_202 7 44:

httQ.s://_www. cidraQ.. umn. edu/_news

QersP-,ective/_2020/_04/_commentarv_-masks-al/-covid-19-not

based-sound-data;

httQ.s://_academic. OUQ.. com/_annweh/_article/_54/_7/_789/_202 7 44

o Filter efficiency was measured across a wide range of small

particle sizes (0.02 to 1 µm) at 33 and 99 L/min.

o All the cloth masks and materials had near zero efficiency at 0.3

µm, a particle size that easily penetrates into the lung (SARS-CoV-

2 is 0.125 µm)


o Efficiency for the entire range of particles

■ T-shirts -10%

■ Scarves -10% to 20%

■ Cloth masks -10% to 30%

■ Sweatshirts - 20% to 40%

■ Towels - 40%

• Study measuring filter efficiency (2014, Korea)

o httg_s:/Laagr. orgLarticlesLaagr-13-06-oa-0201

o Evaluated 44 masks, respirators, and other materials with similar

methods and small aerosols (0.08 and 0.22 µm)

■ N95 FFR filter - >95% efficiency

■ Medical masks - 55% efficiency

■ General {cloth) masks - 38% efficiency

■ Handkerchiefs - 2% {one layer) to 13% (four layers)

efficiency.

• Conclusion: Wearing masks {other than N95) will not be effective at

preventing SARS-CoV-2 transmission, whether worn as source control

or as PPE.

o N95s protect health care workers, but are not recommended for

source control transmission.

o Surgical masks are better than cloth but not very efficient at

preventing emissions from infected patients. Cloth masks must be

3 layers, plus adding static electricity by rubbing with rubber

glove.

o The cloth that serves as the filtration for the mask is meant to trap

particles being breathed in and out. But it also serves as a barrier

to air movement because it forces the air to take the path of least

resistance, resulting in the aerosols going in and out at the sides

of the mask.

o An August 2020 UCSF study suggested that the mask would

decrease the absolute volume of the inoculum. {The


concentrations of bacteria upstream and downstream of the test

devices were measured with an aerodynamic size spectrometer)

htt12.s:/Lucsf. aQQ.. box. comLsLblvo/ kg_Sz0my_dzd82rjks4 wy_leagt036

Human Studies

• Study of correct use of masks (2020, Singapore). 0 btt~//www.medP-agetodav.com/Jnfectiousdiseasef P-ubl ichealth/..8.

6601 0 Overall, data were collected from 714 men and women. Of all ages,

only 90 participants (12.6%) passed the visual mask fit test. About

75% performed strap placement incorrectly, 61% left a "visible gap

between the mask and skin," and about 60% didn't tighten the

nose-clip.

• Study of surgical face mask use in health care workers (2009, Japan).

o httQ.s://.Qubmed.ncbi.nlm.nih.gov/_19216002L

o Masks did not provide benefit in terms of cold symptoms or

getting cold.

• Randomized clinical trial of standard medical/surgical masks in health

care workers (2010, Australia).

o httQs://_onlinelibrartt wilett com/_doi/_eQ.df/_10.1111/j.1750-

2659. 2011.00198.x?fbclid=lwAR3kRYVYDKb0aR-

su9 me9 vY6a8KVR4HZ17J2A B0f fXUABRQdhQ/cBWo.

o Study was spurred by the H1N1 flu. While N95 masks offered

protection against respiratory illness, medical mask wearers and

control group numbers were similar.

• Review of influenza virus and face masks in health care workers

(HCWs) (2010, Hong Kong).

o httQ.s://_www. cam bridge. orgLcore/journalsLeP-.idemio/ogx.-andinfection/_artic/e/jace-masks-to-P-.revent-transmission-of-


influenza-virus-a-sx.stematic

reviewL64D368496EBDE0AFCC6639CCC9DBBC05 0 6 studies of face mask use, both surgical masks and N-95

respirators in HCWs and community settings. The effectiveness of

face masks is probably impacted by compliance issues in both the

healthcare and community setting. Various studies show a lower

level of compliance with face masks or find lower reported

acceptability of face masks compared to hand hygiene behaviors

and other non-pharmaceutical interventions.

• Review of masks against influenza (2012, Europe).

o httg_s:/Lonlinelibrar½wile½CDmLdoiLeg_dfL10.1111/j.1750-

2659.2011. 0030 7. X

o 17 eligible studies. One study had improvement with mask plus

hand sanitizer. None of the studies established a conclusive

relationship between mask/respirator use and protection against

influenza infection.

• *The first randomized controlled trial of cloth masks in health care

workers (2015, Australia).

o httg_s:/Lbmjog_en. bmj. comLcontentL5L4Le0065 77:

httg_s:/Lwww.ncbi.nlm.nih.govfg_mcLarticles/PMC4420971fg_df Lbmj

og_en-2014-006577.g_df

o Penetration of:

■ Cloth masks by particles - 97%

■ Medical masks - 44%,

■ 3M Vflex 9105 N95 - 0.1%

• 3M 9320 N95 - <0.01%

o Cloth masks resulted in significantly higher rates of infection than

medical masks, and also performed worse than the control arm

some of whom may have worn masks.

o The virus may survive on the surface of the face masks

o Self-contamination through repeated use and improper doffing is


possible. A contaminated cloth mask may transfer pathogen from

the mask to the bare hands of the wearer. 0 Moisture retention, reuse of cloth masks, and poor filtration may

result in increased risk of infection.

o Cloth masks should not be recommended for health care workers,

particularly in high-risk situations.

• Review of N95 and surgical masks against respiratory infection (2016).

httg_s:/Lwww. cmaj. caLcontentLcmajL1BBLBL567. f u/1. g_df

o From January 1990 to December 2014. 6 clinical studies: 3

randomized controlled trials (RCTs), 1 cohort study and 2 case-

control studies, and 23 surrogate exposure studies.

o In the meta-analysis of the clinical studies, "no significant

difference between N95 respirators and surgical masks in

associated risk of (a) laboratory-confirmed respiratory infection,

(b) influenza-like illness, or (c) reported work-place absenteeism."

• Review of masks and N95s against respiratory infection (2017,

Singapore).

o httg_s:/Ldoi.orgL10.1093LcidLcix681

o Separate meta-analyses of 6 randomized controlled trials (RCTs)

and 23 observational studies conducted during the 2003 SARS

pandemic.

o Compared to medical masks, N95 respirators provided greater

protection against clinical respiratory illness (CRI) and bacterial

respiratory illness (BRI). These 2 outcomes were common in these

trials (average risks of 8.7% and 7.3%, respectively).

o Compared to masks, N95 respirators conferred superior

protection against clinical respiratory illness and laboratory

confirmed bacterial, but not viral infections or influenza life illness

(ILi).

o Self-reported assessment of clinical outcomes was prone to bias.

o Evidence of a protective effect of masks or respirators against


verified respiratory infection was not statistically significant

(compared to no mask)

• Randomized Controlled Trial: N95s vs medical masks in health care

workers (HCWs) against influenza (2019).

o httg_s://j_amanetwork.com/j_ourna/s/j_amaLfullarticleL2749214

o 2862 randomized participants, 2371 completed the study and

accounted for 5180 HCW-seasons.

o Among outpatient health care personnel, N95 respirators (8.2%)

vs medical masks (7.2%) resulted in no significant difference in the

incidence of laboratory-confirmed influenza. 90% said they wore

the mask all the time.

• Review of N95 respirators versus surgical masks against influenza

(March 2020, China).

o httQ.s:/Ldoi.orgL10.1111/j_ebm.12381

o 6 randomized controlled trials (RCTs) involving 9,171 participants

were included (2015-2020). There were no statistically significant

differences in preventing laboratory-confirmed influenza,

laboratory-confirmed respiratory viral infections, laboratory

confirmed respiratory infection and influenza-like illness using

N95 respirators and surgical masks.

o Meta-analysis indicated a protective effect of N95 respirators

against laboratory-confirmed bacterial colonization.

• CDC Review since 1946 of masks and influenza (May 2020)

o NonQharmaceutical Measures for Pandemic Influenza in

Nonhealthcare Settings-Personal Protective and Environmental

Measures." /J11QS.://wwwnc.cdc.gov/_eid/article/2B/..5/_19-

0994 article o Systematic review. 10 RCTs that reported estimates of the

effectiveness of face masks in reducing laboratory-confirmed

influenza virus infections in the community from literature


published during 1946-July 27, 2018. 0 There is limited evidence for face masks' effectiveness in

preventing laboratory-confirmed influenza virus transmission

either when worn by the infected person for source control or

when worn by uninfected persons to reduce exposure.

o "Proper use of face masks is essential because improper use

might increase the risk for transmission."

• A study of 4 patients (July 2020, South Korea).

o httQ.s:/Lwww. acgjournals. orgLdoiL10. 7326LM20-1342

o Known patients infected with SARS-CoV-2 wore masks and

coughed into a Petrie dish. "Both surgical and cotton masks seem

to be ineffective in preventing the dissemination of SARS-CoV-2

from the coughs of patients with COVID-19 to the environment

and external mask surface."

• Studied different types of face coverings in non-clinical setting (August

2020).

o httg_s:/Ladvances. sciencemag. orgLcontentLearlyL2020L0BL0 7 Lsciad

v.abd3083

o They used a black box, a laser, and a camera. A person wears a

face mask and speaks into the direction of an expanded laser

beam inside a dark enclosure. Droplets that propagate through the

laser beam scatter light, which is recorded with a camera. A

simple computer algorithm then counts the droplets seen in the

video.

o The N95 led to a droplet transmission of below 0.1%.

o Cotton and polypropylene masks, some of which were made from

apron material showed a droplet transmission ranging from 10% to

40%.

o Knitted mask had up to 60% droplet transmission.

o Neck fleece had 110% droplet transmission (10% higher than not

wearing a mask).


o Speaking through some masks (particularly the neck fleece,

bandanas) seemed to disperse the largest droplets into a

multitude of smaller droplets ... which explains the apparent

increase in droplet count relative to no mask in that case.

• See "Positive Effects of Masks" below. A recent study suggested that

the mask would decrease the absolute volume of the inoculum. (The

concentrations of bacteria upstream and downstream of the test

devices were measured with an aerodynamic size spectrometer)

httQ.s:/Lucsf.aQQ..box.comLsLblvolkQ.5zOmx_dzd82rjks4wy_/eagt036

• Austrian observation (August 2020)

o httQ.s./Lcorona-transition.orgLmaskenQ.flicht-brachte-in

osterreich-keinerlei-messbaren-nutzen (in German)

o The introduction, retraction and re-introduction of mandatory face

masks in Austria had no influence at all on the infection rate.

• News reCQ.Ct (August 13, 2020) 0 blt~//sentinelksmo.org/_more-deceP-.tion-kdhe-hid-data-to

justifv_-mask-mandateL

o In Kansas, the 90 counties without mask mandates had lower

coronavirus infection rates than the 15 counties with mask

mandates. To hide this fact, the Kansas health department tried to

manipulate the official statistics and data presentation.

Study from France:


"' ~ "' "' u ~

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"' :l ... ·;; "' C: 0 ... 0 u ~ > 0 z

10k

7.Sk

Sk

2.Sk

0

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Daily New Cases Cases per Day

Data as of 0:00 GMT +O

bilQ..S..;/.~QLS....Q[g/face-masks-evidence/. (Swiss Policy Research)

Johns Hopkins, 9/21/20

Indoor Mask Mandate

New Confirmed CCVI D-19 Cases per Day, normalized by population

120

100

80

60

40

20

0

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'c3 3 • z

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httQs ://.twi tter.comLC ovi d 19C rush er /.statu s/.1308013 900 5464 2 8 9 2 8

Negative Effects of Masks

Spain

Look Mum, no mask !

0 '-------~Sweden

Dllys sine• 1 cllse/lm people


Air inside the mask is definitely stale. In filtering particles, the mask makes

it harder to breathe.

Decreased Pa02

• A 2004 observational study of end stage renal disease patients during

dialysis for 4 hours (2004, Taiwan).

o httg_s./jg_ubmed.ncbi.nlm.nih.govL15340662/_;

o httg_s:/Lwww.researchgate.netfg_ublicationL8371248 The g_hy_sio/og

ical_img_act of wearing an N95 mask during hemodialy_sis_as_g_Q

recaution against SAR$ in g_atients with end-stage renal disease

o 39 patients, mean age, 57 years. 70% had decreased PaO2 (from

100 to 92); 19% had hypoxemia (PaO2 <70); all patients had

increased respiratory rate 16 to 18; chest discomfort (3 baseline

patients to 11 patients); respiratory distress (1 baseline patient to

17 patients)

• Stanford engineers estimated that N95 masks cause a 5% to 20%

reduction in 02 intake. This can cause dizziness and lightheadedness.

This can be life-threatening for someone with lung disease or with

respiratory distress. 0 b1..tps:/Lengineering. stanford. edu/_magazine/articleLcovid-19-

promP-,ts-team-engineers-rethink-humble-face-mask

• Study of surgeons in the OR (2008, Turkey).

o httP-.:fLscielo. isciii. esf P-.df LneuroLv19n2L3. P-,df o Scientists looked at 02 levels of surgeons wearing masks while

performing surgery. Found a decrease in the oxygen saturation of

arterial pulsations (peripheral capillary 02 saturation/SpO2) fell

from 98% to 96% and a slight increase in pulse rates compared to

preoperative values in all surgeon groups.

Increased CO2


• This may be merely theoretical. Carbon dioxide molecules freely

diffuse through the masks, allowing normal gas exchange while

breathing.

• CO2 is present in the atmosphere at a level of about 0.04% ·(400ppm).

According to the U.S. Department of Agriculture / OSHA, carbon

dioxide becomes toxic at concentrations above 4 percent

(40,000ppm); symptoms at 5,000-10,000 ppm. 10,000 ppm has been

measured behind mask.

• Experiment (July 2020).

o h ttQ.s://_www.wthr.com/_a rtic/e/_ne ws/_hea I th/_ corona vi rus/_verify_-do

f ace-masks-reduce-oxygen-intake-carbon-di oxide-ex 12.eri men t -

multiQ.le-maskssL531-c00c96cb-9273-4947-949c-

0807f94454a7

o Pulse oximeter and exhaled CO2 (via tube in mask) No change

with mask. (End-tidal capnography or end-tidal CO2 (EtCO2)

monitoring is a non-invasive technique that measures the partial

pressure or maximal concentration of carbon dioxide (CO2) at the

end of an exhaled breath. The normal values are 5-6% CO2, which

is equivalent to 35-45 mmHg.)

• Health care worker study (2005, Scandinavia)

o httQ.s:/f P-.ubmed.ncbi.nlm.nih.gov/_16441251L

o 37.3% reported face-mask-associated headaches, 32.9% reported

headache frequency >6 times per month. 7.6% had taken sick

leave from March 2003 to June 2004 (mean 2 days; range 1-4

days) and 59.5% required use of abortive analgesics because of

headache.

• Health care worker study (2009, Japan) with similar headache results

as Scandinavian study (above).

o htt~/fpubmed.ncbi.nlm.nih.govL19216002L


• While there are some articles reporting OSHA tests, it is not clear they

were proper tests.

• Some people have mistakenly claimed that OSHA standards (e.g., the

Respiratory Protection standard, 29 CFR 1910.134; the Permit-Required

Confined Space standard 29 CFR 1910.146; and the Air Contaminants

standard, 29 CFR 1910.1000) apply to the issue of oxygen or carbon

dioxide levels resulting from the use of medical masks or cloth face

coverings in work settings with normal ambient air (e.g. healthcare

settings, offices, retail settings, construction). These standards do not

apply to the wearing of medical masks or cloth face coverings in work

settings with normal ambient air). These standards would only apply to

work settings where there are known or suspected sources of

chemicals (e.g., manufacturing facilities) or workers are required to

enter a potentially dangerous location (e.g., a large tank or vessel).

httQ.s:/Lwww.osha.gov LSL TCLcovid-19Lcovid-19-fag. html

• It is hard to tell if the headaches experienced by HCWs with N95s is

CO2 or having a strap around the head.

• But when asked should we be worried about CO2, mask proponents

say, "No" because you can exhale around the sides of the mask. This

defeats the purpose. (2006)

httQ.s://.Q.ubmed.ncbi.nlm.nih.govL16441251L

Moisture retention

• Reuse of cloth masks, frequency and effectiveness of cleaning, and

poor filtration may result in increased risk of infection.

• Observations during SARS suggested double-masking and other

practices increased the risk of infection because of moisture, liquid

diffusion.

o httQ.s:/LbmjoQ.en. bmj. comLcontentL5L4Le006577:


httQ.s:/Lwww.ncbi.nlm.nih.govfQ.mcLartic/es/PMC4420971fQ.dfLbmj

og_en-2014-006577.g_df

• Recent study {in German) cultured 82 bacterial colonies & 4 mold

{fungoid) colonies from a child's masks after 8 hours of wear. 0 httg_s:/Ltwitter. comLM MaccruiskeenLstatusL130 726652 766266982

5?s=20

Self-contamination

• Contamination through repeated use and improper doffing is possible.

The virus may survive on the surface of the mask. The pathogen goes

from mask to bare hands.

"Mask mouth"

• Reported by dentists. httg_s:/!JJ.Y.g_ost.comL2020LOBL05Lmask-mouth

is-a-seriouslv_-stinkv_-side-effect-of-wearing-masksL

• Wearing masks increases dryness, which leads to decrease in saliva. It

is the saliva that fights bacteria. Result is decaying teeth, receding gum

lines and seriously sour breath. Gum disease - or periodontal disease

- will eventually lead to strokes and an increased risk of heart

attacks."

World Health Organization {WHO), June 2020

• .bllQ.S.;/.La.p_ps.who. i nt/.iris/.bitstream/.ha nd le/.10665/332293/.WH 0- 2019-nCov-l PC Masks-2020.4-eng.,pdf?sequence=1&isAllowed=y_

• "The likely disadvantages of the use of mask by healthy people in the

general public include:

o potential increased risk of self-contamination due to the

manipulation of a face mask and subsequently touching eyes with

contaminated hands;

o potential self-contamination that can occur if non- medical masks


are not changed when wet or soiled. This can create favourable

conditions for microorganism to amplify;

o potential headache and/or breathing difficulties, depending on

type of mask used;

o potential development of facial skin lesions, irritant dermatitis or

worsening acne, when used frequently for long hours;

o difficulty with communicating clearly;

o potential discomfort;

o a false sense of security, leading to potentially lower adherence to

other critical preventive measures such as physical distancing and

hand hygiene;

o poor compliance with mask wearing, in particular by young

children;

o waste management issues; improper mask disposal leading to

increased litter in public places, risk of contamination to street

cleaners and environment hazard;

o difficulty communicating for deaf persons who rely on lip reading;

o disadvantages for or difficulty wearing them, especially for

children, developmentally challenged persons, those with mental

illness, elderly persons with cognitive impairment, those with

asthma or chronic respiratory or breathing problems, those who

have had facial trauma or recent oral maxillofacial surgery, and

those living in hot and humid environments.

The Hamburg Environmental Institute (July 2020) warned of the inhalation

of chlorine compounds in polyester masks as well as problems in

connection with face mask disposal. httgs:LLswgrs.orgLface-masks

evidenceL; httgs:LLcorona-transition.orgLmaskentragen-noch-ungesunder

als-gedacht (in German)

Psychological Damage in Children (September 11, 2020).

httQ.s:/Lwww.world-todax_-news.com/_70-doctors-in-open-letter-to-ben

wex_ts-abolish-mandatorx_-mouth-mask-at-schoo/-belgiumL


• 70 Belgian doctors begged for cancellation of mask mandate at school.

"In recent months, the general well-being of children and young people

has come under severe pressure. We see in our practices an increasing

number of children and young people with complaints due to the rules

of conduct that have been imposed on them. We diagnose anxiety and

sleep problems, behavioral disorders and fear of contamination. We are

seeing an increase in domestic violence, isolation and deprivation.

Many lack physical and emotional contact; attachment problems and

addiction are obvious. 'The mandatory mouth mask in schools is a major threat to their development. It ignores the essential needs of the growing child. The well-being of children and young people is highly dependent on the emotional connection with others. ( ... ) The aim of education is to create an optimal context so that a maximum

development of young people is possible. The school environment

must be a safe practice field. The mouth mask obligation, on the other hand, makes the school a threatening and unsafe environment, where emotional connection becomes difficult. 'In addition, there is no large-scale evidence that wearing face masks in a non-professional environment has any positive effect on the spread of viruses, let alone on general health.'

Unanswered questions

• Can virions escape an evaporating droplet stuck to a mask fiber?

• What are long-term health effects on HCW, such as headaches, arising

from impeded breathing?

• Are there negative social consequences to a masked society?

• Are there negative psychological consequences to wearing a mask, as

a fear-based behavioral modification?

• What are the environmental consequences of mask manufacturing and

disposal?

Positive Mask Studies


• Some cite a September 2019 study mentioned above

(httg_s:j/jamanetwork.com/journa/s/jamaLfullarticleL2749214J

comparing N95s and surgical masks in preventing flu. BUT there was

no control wearing no mask. The point of the study found that both

types had similar incidence of flu. {N95-8.2% vs 7.2%).

• The main study used is the Missouri hairdressers who were SARS-CoV-

2 infected but asymptomatic and wore a mask; clients did not get

infected.{July 2020)

o httg_s:/Lwww. livescience. comLhair-sty_lists-infected-covid19-face

masks. html:

o httg_s:f Lwww.cdc.gov Lmmwr LvolumesL69Lwr Lmm692 Be 2. htm

o But there is a Chinese report {May [August] 2020) of a COVID

infected asymptomatic person who did not infect 455 persons

with whom he was in contact.

httg_s:ffg_ubmed.ncbi.nlm.nih.govL32513410L

o Asymptomatic people do not cough and sneeze. But one study

showed they shed just as many viruses as symptomatic. {August

2020, Korea)

o h ttg_s:f /ja mane twork. com/j o u rna I s/ja main tern a I med ici neLf u Ila rt i cl eL

2769235

• Review of mask use {March 2020, multi-country)

o httg_s:/Lwww.sciencedirect.comLscienceLarticleLg_iiLS14778939203

02301?via%3Dihub

o 21 studies; 8,686 participants. Mask use by health care workers

{HCWs) and non-HCWs. HCWs had 80% reduction of viral

infections. Non-HCW had 56%. Asian better than Western. Study

stressed that masks were an adjunct to other measures.

o Other factors:

■ Older age of the population, urbanization, obesity, and longer

duration of the outbreak in a country were independently

associated with higher country-wide per-capita coronavirus


mortality.

■ International travel restrictions were associated with lower

per-capita mortality.

■ Other containment measures, testing and tracing polices, and

the amount of viral testing were not statistically significant

predictors of country-wide coronavirus mortality, after

controlling for other predictors.

■ Societal norms and government policies supporting mask

wearing by the public were independently associated with

lower per-capita mortality from COVID-19.

• Review of 8 pre-COVID-19 studies (June 2020, Australia).

o httQ.s:/.Lwww. ncbi. nlm. nih. gov /.Q.mcLarticles/.PMC 732 322 3L?

fbclid=lwAR2Uky_t8GCrK-goc

bgCJhHknW5Q.gy_tBFOfe6txHWI 7eUs9Q.8vsrQ26KIM

o Surgical masks reduced influenza like illnesses (ILi) by 41% and

N95 by 66% (difference was not statistically significant). Save N95

for aerosols.

o No good evidence face masks protect the public against viral

respiratory illnesses

o "Australia and New Zealand currently, the questionable benefits

arguably do not justify health-care staff wearing surgical masks

when treating low-risk patients and may impede the normal caring

relationship between patients, parents and staff."

• Review of masks, physical distancing, eye protection (June 2020,

WHO).

o httQ.s./Lwww. the lancet. com/j_ournalsLJancetLarticle/.PIIS014 0-6736 (.20) 31142-9/julltext

o 172 observational studies across 16 countries and six continents;

MERS, SARS, betacorona, SARS-CoV-2 in health care and non

healthcare settings. N95s better than surgical or 12 layer cotton.

Authors did not rate the certainty of effect as high. Findings were


in accord with those of a cluster randomized trial showing a

potential benefit of continuous N95 respirator use over medical

masks against seasonal viral infections.

• Review of face mask efficacy (July 2020, China).

o httg_s:/Lwww.ncbi.nlm.nih.govfg_mcLarticlesLPMC7253999:

o httg_s:/Lwww.sciencedirect.comLscienceLarticlefg_iiLS14778939203

02301?via%3Dihub

o 21 studies, 8,686 participants: 13 case-control studies, 6 cluster

randomized trials, and 2 cohort studies. 12 studies of health care

workers (HCWs); 8 studies of non-healthcare professional

populations; 1 study of HCWs and relatives of patients. SARS,

H1N1, influenza lab confirmed.

o Masks (N95 and surgical) were generally effective in preventing

the spread of respiratory viruses. After wearing a mask, the risk of

contracting RVls was significantly reduced. Use of masks by

HCWs and non-HCWs can reduce the risk of respiratory virus

infection by 80% and 47% respectively.

o The study they reference regarding "social" masks is footnoted to

a model that assumes complete compliance and universality.

• CDC review of masks and antibody presence in health care workers

(HCWs) (September 2020).

o httg_s:/Lwww.cdc.govLmmwrLvolumesL69LwrLmm6935e2.htm?

~ cid=mm6935e2 w

o 3,248 HCWs observed. 6% had antibodies to SARS-CoV-2; 29%

were asymptomatic; 69% had not had a diagnosis of SARS-Co-V-

2 infection. Prevalence of antibodies was lower (6%) in HCWs who

wore masks that those who did not (9%).

• *Experiment (human) measuring surgical mask efficacy in reducing

virus transmission (April 2020, Hong Kong).

o b.11~//_www.nature.com/_articles/_s41591-020-0843-2


0 246 participants. Infection measured by PCR. Bioaerosol

collecting device, to capture exhaled breath particles. Two size

fractions: < and >5 microns. Surgical masks can efficaciously

reduce the emission of influenza virus particles into the

environment in respiratory droplets, but not in aerosols. Surgical

face masks could be used by ill people to reduce onward

transmission.

• Summer 2020 study with laboratory coughs (Summer 2020)

o httQ.s:fLwww.vumedi.comLvideoLairborne-transmission-face

masks-how-do-different-txQ.es-of-masks-Q.rotect-against

various-ranges-of-ti

Forward motion distance:

■ Handkerchief - 4 feet

■ 3 layer cloth - 1 foot

■ 2 layers sewn cloth-- 2-3 inches

■ Problems:

■ But drops go around the nose and sides of mask.

■ Shields only work for large droplets.

■ Exhalation ports reduce humidity but defeat the purpose

of using the mask.

• A U.S. study of airborne transmission (May 2020)

o httQ.s:fLwww.Q.nas.orgLcontentL117L26L14857

o Study claimed that masks had led to a decrease in infections in

three global hotspots (including New York City). This did not take

into account the natural decrease in infections and other

measures. The study was so flawed that over 40 scientists

recommended that the study be withdrawn.

• A U.S. study comparing states with mask mandates {June 2020).

o btt~/Lwww.healthaffairs.org/doiLfulf/_10.1377/_hlthaff.2020.00818

o Study concluded that mandatory masks had led to a decrease in


infections in 15 states. The study did not take into account that the

incidence of infection was already declining in most states at that

time. A comparison with other states was not made.

• A U.S. study comparing masks, lockdowns in various countries (June

2020).

o httgs:/Lwww.medrxiv.orgLcontentL10.1101L2020.05.22.20109231v3

.fu/1.gdf

o Study concluded that countries with mandatory masks had fewer

deaths than countries without mandatory masks. But the study

compared African, Latin American, Asian and Eastern European

countries with very different infection rates and population

structures.

• * July-August 2020- UCSF - Mask can be a crude "vaccine."

o httgs://jink. SQ.ringer. comLarticleL10.1007 Ls11606-020-06067-8;

o httgs:/Lucsf. aQQ.. box. comLsLblvolkg5z0my_dzd82rjks4 wy_leagt036:

o httgs:/Lwww.neim.orgLdoiLfullL10.1056LNEJMg2026913:

o h ttgs:/Legibiostat. ucsf. eduLnewsLnew-theory_-asks-could-mask

be-crude- 'vaccine';

o httgs:/Lwww. vumedi. comLvideoLcovid-19-mortality_-ugdate-does

masking-reduce-vira/-inoculum-to-which-wearer-is-exgosedL

o Universal masking reduces the "inoculum" or dose of the virus for

the mask-wearer, leading to more mild and asymptomatic infection

manifestations similar to variolation with small pox. CDC estimates

40% asymptomatic. But masked cruise ship folks had 81%

asymptomatic, 95% masked prison folks, food processing plants.

(The concentrations of bacteria upstream and downstream of the

test devices were measured with an aerodynamic size

spectrometer.)

• Many studies ignore the effect of other measures, the natural

development of infection numbers, changes in test activity, or they


compare countries with very different conditions.

Conclusions from Organizations

• The World Health Organization (WHO): (April 6, 2020) o httP-s:LLaQP-S.who.intLirisLbitstreamLhandleL10665L331693LWHO-

2 019-nCov-l PC Masks-20 2 0 .3-eng.!P-df ?seg uence = 1 &i sAI I owed =y_

o "Advice to decision makers on the use of masks for healthy people in community settings:

o The wide use of masks by healthy people in the community setting

is not supported by current evidence and carries uncertainties and

critical risks."

o "Medical masks should be reserved for health care workers. The use of medical masks in the community may create a false

sense of security, with neglect of other essential measures, such

as hand hygiene practices and physical distancing, and may lead

to touching the face under the masks and under the eyes, result in

unnecessary costs, and take masks away from those in health care

who need them most, especially when masks are in short supply."

o "Masks are effective only when used in combination with frequent hand-cleaning with alcohol-based hand rub or soap and water." WHO acknowledges that most people do not use masks properly.

• But in June 8, 2020

o httg_s:/Lagg_s. who. intfjrisLbitstreamLhandleL10665L332293LWHO-

2019-nCov-/ PC Masks-2020.4-eng.pdf?seguence=1&isAl/owed=.Y-

o The World Health Organization has changed its stance on wearing

face masks during the COVID-19 pandemic. People over 60 and

people with underlying medical conditions should wear a medical

grade mask when they're in public and cannot socially distance.

The general public should wear a three-layer fabric mask in those

situations. Admitting that this was despite evidence with

randomized controlled trials. "The use of a mask alone is


insufficient to provide an adequate level of protection or source

control, and other personal and community level measures should

also be adopted to suppress transmission of respiratory viruses." 0 The reasons for recommending masks has little to do with

effectiveness. "The likely advantages of the use of masks by

healthy people in the general public include:

o reduced potential exposure risk from infected persons before they

develop symptoms;

o reduced potential stigmatization of individuals wearing masks to

prevent infecting others (source control) or of people caring for

COVID-19 patients in non-clinical settings;

o making people feel they can play a role in contributing to stopping

spread of the virus;

o reminding people to be compliant with other measures (e.g., hand

hygiene, not touching nose and mouth).

o potential social and economic benefits.

■ Amidst the global shortage of surgical masks and PPE,

encouraging the public to create their own fabric masks may

promote individual enterprise and community integration.

■ the production of non-medical masks may offer a source of

income for those able to manufacture masks within their

communities.

■ Fabric masks can also be a form of cultural expression,

encouraging public acceptance of protection measures in

general.

■ The safe re-use of fabric masks will also reduce costs and

waste and contribute to sustainability."

• Dr. Nancy Messonnier, director of the Center for the National Center

for Immunization and Respiratory Diseases (January 31, 2020):

o httQ.s:fLwww.cdc.gov Lmedia/Je/easesL2020Lt0131-2019-novel

coronavirus. html

o "We don't routinely recommend the use of face masks by the APPENDIX TO JAMES CASCIANO DECLARATION-40

public to prevent respiratory illness .... And we certainly are not

recommending that at this time for this new virus."

• The Centers for Disease Control and Prevention (CDC)

o httg_s:/Lwww.cdc.gov Lf lufQ.rofessiona/sfjnfectioncontro/Lmaskguida

nce.htm

o In March 5, 2019 regarding the flu: "Masks are not usually

recommended in non-healthcare settings; however, this guidance

provides other strategies for limiting the spread of influenza

viruses in the community":

o *Cover their nose and mouth when coughing or sneezing,

o *Use tissues to contain respiratory secretions and, after use, to

dispose of them in the nearest waste receptacle, and

o *Perform hand hygiene (e.g., handwashing with non-antimicrobial

soap and water, and alcohol-based hand rub if soap and water are

not available) after having contact with respiratory secretions and

contaminated objects/materials.

• On August 7, 2020

o Masks are recommended as a simple barrier to help prevent

respiratory droplets from traveling into the air and onto other

people when the person wearing the mask coughs, sneezes, talks,

or raises their voice. This is called source control.

o CDC recommends that people wear masks in public settings and

when around people who don't live in your household, especially

when other social distancing measures are difficult to maintain.

o Masks may help prevent people who have COVID-19 from

spreading the virus to others.

o Masks are most likely to reduce the spread of COVID-19 when

they are widely used by people in public settings.

o Masks should NOT be worn by children under the age of 2 or

anyone who has trouble breathing, is unconscious, incapacitated,

or otherwise unable to remove the mask without assistance.

o Masks with exhalation valves or vents should NOT be worn to help APPENDIX TO JAMES CASCIANO DECLARATION-41

prevent the person wearing the mask from spreading COVID-19 to

others (source control).

• From the New England Journal of Medicine, Universal Masking in the

Covid-19 Era, July 9, 2020;

o httQs:/Lwww.nejm.orgLdoi/jullL10.1056LNEJMQ2006372

o "We know that wearing a mask outside health care facilities offers

little, if any, protection from infection. Public health authorities

define a significant exposure to Covid-19 as face-to-face contact

within 6 feet with a patient with symptomatic Covid-19 that is

sustained for at least a few minutes (and some say more than 10

minutes or even 30 minutes). The chance of catching Covid-19

from a passing interaction in a public space is therefore minimal. In

many cases, the desire for widespread masking is a reflexive

reaction to anxiety over the pandemic." It is also clear that masks

serve symbolic roles. Masks are not only tools, they are also talismans that may help increase health care workers' perceived sense of safety, well-being, and trust in their

hospitals. Although such reactions may not be strictly logical, we

are all subject to fear and anxiety, especially during times of crisis.

One might argue that fear and anxiety are better countered with

data and education than with a marginally beneficial mask.

o But later authors said, "A growing body of research shows that the

risk of SARS-CoV-2 transmission is strongly correlated with the

duration and intensity of contact: the risk of transmission among

household members can be as high as 40%, whereas the risk of

transmission from less intense and less sustained encounters is

below 5%. This finding is also borne out by recent research

associating mask wearing with less transmission of SARS-CoV-2,

particularly in closed settings."

httQ.s:/Lwww.nejm.orgLdoiLfullL10.1056LNEJMc2020836

• Holland's Medical Care Minister Tamara van Ark


0 httgs:fLwww. thesu n .co. u kLnewsL u knewsL12 29 2 8 21 /.face-mas ks

not-necessa ry_-say_-ho I la nd-scienti stsL

o "Despite a global stampede of mask-wearing, data show that 80-

90 percent of people in Finland and Holland say they "never" wear

masks when they go out, a sharp contrast to the 80-90 percent of

people in Spain and Italy who say they "always" wear masks when

they go out. "From a medical point of view, there is no evidence of

a medical effect of wearing face masks, so we decided not to

impose a national obligation."

• Panel, Rational use of face masks in the COVID-19 pandemic (March

2020) o httgs:f/.www.ncbi.nlm.nih.gov/.gmc/articles/.PMC7118603L o Recommendations on face mask use in community settings

• WHO

■ If you are healthy, you only need to wear a mask if you

are taking care of a person with suspected SARS-CoV-2

infection.

■ China

■ People at moderate risk~ of infection: surgical or

disposable mask for medical use.

■ People at low risk~ of infection: disposable mask for

medical use.

■ People at very low risk= of infection: do not have to wear

a mask or can wear non-medical mask (such as cloth

mask).

■ Hong Kong

■ Surgical masks can prevent transmission of respiratory

viruses from people who are ill. It is essential for people

who are symptomatic (even if they have mild symptoms)

to wear a surgical mask.

■ Wear a surgical mask when taking public transport or

staying in crowded places. It is important to wear a mask


properly and practice good hand hygiene before wearing

and after removing a mask.

■ Singapore

■ Wear a mask if you have respiratory symptoms, such as a

cough or runny nose.

■ Japan

■ The effectiveness of wearing a face mask to protect

yourself from contracting viruses is thought to be limited.

If you wear a face mask in confined, badly ventilated

spaces, it might help avoid catching droplets emitted

from others but if you are in an open-air environment, the

use of face mask is not very efficient.

■ USA ■ Centers for Disease Control and Prevention does not

recommend that people who are well wear a face mask

(including respirators) to protect themselves from

respiratory diseases, including COVID-19.

■ US Surgeon General urged people on Twitter to stop

buying face masks

■ UK ■ Face masks play a very important role in places such as

hospitals, but there is very little evidence of widespread

benefit for members of the public.

■ Germany

Final Thoughts

■ There is not enough evidence to prove that wearing a

surgical mask significantly reduces a healthy person's

risk of becoming infected while wearing it. According to

WHO, wearing a mask in situations where it is not

recommended to do so can create a false sense of

security because it might lead to neglecting fundamental

hygiene measures, such as proper hand hygiene.


• Surgical masks are loose fitting. They are designed to protect the

patient from the doctors' respiratory droplets. There wearer is not

protected from others' airborne particles.

• People do not wear masks properly. Many people have the mask under

the nose. The wearer does not have glasses on and the eyes are a

portal of entry. If the virus lands on the conjunctiva, tears will wash it

into the nasopharynx.

• Most studies cannot separate out hand hygiene.

• The designer masks and scarves offer minimal protection. They give a

false sense of security to both the wearer and those around the wearer.

**Not to mention they add a perverse lightheartedness to the situation.

• If you are walking alone, no need for a mask. Avoid other folks; use

common sense.

• Remember: children under 2 years should not wear masks because of

accidental suffocation and difficulty breathing in some.

• Even if a universal mask mandate were imposed, several studies noted

that folks do not use the mask properly and over-report their wearing.

Additionally, how would the mandate be enforced??

• The positive studies are models that assume universality and full

compliance.

• If wearing a mask makes people go out and get Vitamin D - go for it. In

the 1918 flu pandemic people who went outside did better. Early

reports are showing people with COVID-19 with low Vitamin D do

worse than those with normal levels. Perhaps that is why shut-ins do

so poorly.

htt{J.s:/Lwww.medrxiv.orgLcontentL10.1101L2020.04.08.20058578v4

Wash your hands --- If you are sick, stay home!

Objects and surfaces

• Person to person touching

• The CDC's most recent statement regarding contracting COVID-19


from touching surfaces: "Based on data from lab studies on Covid-19

and what we know about similar respiratory diseases, it may be

possible that a person can get Covid-19 by touching a surface or

object that has the virus on it and then touching their own mouth, nose

or possibly their eyes," the agency wrote. "But this isn't thought to be

the main way the virus spreads.

httQs:/Lwww.cdc.gov Lmedia/_releases/_2020/_s0522-cdc-uQ.dates-covid

transmission. html.

• Chinese study with data taken from swabs on surfaces around the

hospital (July 2020)

o httQ.s:/Lwwwnc. cdc. gov LeidLarticleL26/.7L20-088 5 article?

delivery_Name=USCDC 333-DM25707

o The surfaces where tested with the PCR (polymerase chain

reaction) test, which greatly amplifies the viral genetic material if it

is present. That material is detectable when a person is actively

infected. At the time of the study, it was thought to be the most

reliable test. Because of the amplification of the viral material,

there are many false positives. It is not clear that the mere

presence of virus means it is infectious.

■ Computer mouse (ICU 6/8, 75%; General ward (GW) 1/5,

20%)

■ Trash cans {ICU 3/5, 60%; GW 0/8)

■ Sickbed handrails (ICU 6/14, 42.9%; GW 0/12)

■ Doorknobs {GW 1/12, 8.3%)

■ 81.3% of the miscellaneous personal items were positive:

■ Exercise equipment

■ Medical equipment (spirometer, pulse oximeter, nasal

cannula)

■ PC and iPads

■ Reading glasses

■ Cellular phones (83.3% positive for viral RNA)

■ Remote controls for in-room TVs (64.7% percent


positive)

■ Toilets (81.0% positive)

• Room surfaces (80.4% of all sampled)

• Bedside tables and bed rails (75.0%)

■ Window ledges (81.8%)

■ Plastic: up to 2-3 days

■ Stainless Steel: up to 2-3 days

■ Cardboard: up to 1 day

■ Copper: up to 4 hours

■ Floor - gravity causes droplets to fall to the floor. Half of

ICU workers all had virus on the bottoms of their shoes


Mask use in the context of COVID-19

Interim guidance

1 December 2020

This document, which is an update of the guidance published on 5 June 2020, includes new scientific evidence relevant to the use of masks for reducing the spread of SARS-Co V-2, the virus that causes COVID-19, and practical considerations. It contains updated evidence and guidance on the following: • mask management; • SARS-CoV-2 transmission; • masking in health facilities in areas with community,

cluster and sporadic transmission; • mask use by the public in areas with community and

cluster transmission; • alternatives to non-medical masks for the public; • exhalation valves on respirators and non-medical masks; • mask use during vigorous intensity physical activity; • essential parameters to be considered when

manufacturing non-medical masks (Annex).

Key points

• The World Health Organization (WHO) advises the use of masks as part of a comprehensive package of prevention and control measures to limit the spread of SARS-CoV-2, the virus that causes COVID-19. A mask alone, even when it is used correctly, is insufficient to provide adequate protection or source control. Other infection prevention and control (IPC) measures include hand hygiene, physical distancing of at least I metre, avoidance of touching one's face, respiratory etiquette, adequate ventilation in indoor settings, testing, contact tracing, quarantine and isolation. Together these measures are critical to prevent human-to-human transmission of SARS-Co V-2.

• Depending on the type, masks can be used either for protection of healthy persons or to prevent onward transmission (source control).

• WHO continues to advise that anyone suspected or confirmed of having COVID-19 or awaiting viral laboratory test results should wear a medical mask when in the presence of others (this does not apply to those awaiting a test prior to travel).

• For any mask type, appropriate use, storage and cleaning or disposal are essential to ensure that they are as effective as possible and to avoid an increased transmission risk.

Mask use in health care settings • WHO continues to recommend that health workers (1)

providing care to suspected or confirmed COVID-19

1 For adequate ventilation refer to regional or national institutions or heating, refrigerating and air-conditioning societies enacting ventilation requirements. If not available or applicable, a

• World Health Organization

patients wear the following types of mask/respirator in addition to other personal protective equipment that are part of standard, droplet and contact precautions:

- medical mask in the absence of aerosol generating procedures (AGPs)

- respirator, N95 or FFP2 or FFP3 standards, or equivalent in care settings for COVID-19 patients where AGPs are performed; these may be used by health workers when providing care to COVID-19 patients in other settings if they are widely available and if costs is not an issue.

• In areas of known or suspected community or cluster SARS-CoV-2 transmission WHO advises the following:

- universal masking for all persons (staff, patients, visitors, service providers and others) within the health facility (including primary, secondary and tertiary care levels; outpatient care; and long-term care facilities)

- wearing of masks by inpatients when physical distancing of at least 1 metre cannot be maintained or when patients are outside of their care areas.

• In areas of known or suspected sporadic SARS-CoV-2 transmission, health workers working in clinical areas where patients are present should continuously wear a medical mask. This is known as targeted continuous medical masking for health workers in clinical areas;

• Exhalation valves on respirators are discouraged as they bypass the filtration function for exhaled air by the wearer.

Mask use in community settings • Decision makers should apply a risk-based approach

when considering the use of masks for the general public. • In areas of known or suspected community or cluster

SARS-Co V-2 transmission: - WHO advises that the general public should

wear a non-medical mask in indoor ( e.g. shops, shared workplaces, schools - see Table 2 for details) or outdoor settings where physical distancing of at least 1 metre cannot be maintained.

- If indoors, unless ventilation has been be assessed to be adequate 1, WHO advises that the general public should wear a non-medical mask, regardless of whether physical distancing of at least I metre can be maintained.

recommended ventilation rate of IO Vs/person should be met (except healthcare facilities which have specific requirements). For more infonnation consult "Coronavirus (COVID-19) response

- Individuals/people with higher risk of severe complications from COVID-19 (individuals ::::. 60 years old and those with underlying conditions such as cardiovascular disease or diabetes mellitus, chronic lung disease, cancer, cerebrovascular disease or immunosuppression) should wear medical masks when physical distancing of at least 1 metre cannot be maintained.

• In any transmission scenarios: - Caregivers or those sharing living space with

people with suspected or confirmed COVID-19, regardless of symptoms, should wear a medical mask when in the same room.

Mask use in children (2) • Children aged up to five years should not wear masks

for source control. • For children between six and 11 years of age, a risk

based approach should be applied to the decision to use a mask; factors to be considered in the risk-based approach include intensity of SARS-Co V-2 transmission, child's capacity to comply with the appropriate use of masks and availability of appropriate adult supervision, local social and cultural environment, and specific settings such as households with elderly relatives, or schools.

• Mask use in children and adolescents 12 years or older should follow the same principles as for adults.

• Special considerations are required for immunocompromised children or for paediatric patients with cystic fibrosis or certain other diseases (e.g., cancer), as well as for children of any age with developmental disorders, disabilities or other specific health conditions that might interfere with mask wearing.

Manufacturing of non-medical <fabric} masks (Annex} • Homemade fabric masks of three-layer structure (based

on the fabric used) are advised, with each layer providing a function: 1) an innermost layer of a hydrophilic material 2) an outermost layer made of hydrophobic material 3) a middle hydrophobic layer which has been shown to enhance filtration or retain droplets.

• Factory-made fabric masks should meet the minimum thresholds related to three essential parameters: filtration, breathability and fit.

• Exhalation valves are discouraged because they bypass the filtration function of the fabric mask rendering it unserviceable for source control.

Methodology for developing the guidance

Guidance and recommendations included in this document are based on published WHO guidelines (in particular the WHO Guidelines on infection prevention and control of epidemic-and pandemic-prone acute respiratory infections in health care) (2) and ongoing evaluations of all available scientific evidence by the WHO ad hoc COVID-19 Infection Prevention and Control Guidance Development Group (COVID-19 IPC GOG) (see acknowledgement section for list of GOG members). During emergencies WHO publishes interim guidance, the development of which follows a

resources from ASHRAE and others'' https:/ /www .ashrae.org/technical-resources/resources

transparent and robust process of evaluation of the available evidence on benefits and harms. This evidence is evaluated through expedited systematic reviews and expert consensusbuilding through weekly GOG consultations, facilitated by a methodologist and, when necessary, followed up by surveys. This process also considers, as much as possible, potential resource implications, values and preferences, feasibility, equity, and ethics. Draft guidance documents are reviewed by an external review panel of experts prior to publication.

Purpose of the guidance

This document provides guidance for decision makers, public health and IPC professionals, health care managers and health workers in health care settings (including long-term care and residential), for the public and for manufactures of nonmedical masks (Annex). It will be revised as new evidence emerges.

WHO has also developed comprehensive guidance on IPC strategies for health care settings (3), long-term care facilities (LTCF) (4), and home care (5).

Background

The use of masks is part of a comprehensive package of prevention and control measures that can limit the spread of certain respiratory viral diseases, including COVID-19. Masks can be used for protection of healthy persons ( worn to protect oneself when in contact with an infected individual) or for source control ( worn by an infected individual to prevent onward transmission) or both.

However, the use of a mask alone, even when correctly used (see below), is insufficient to provide an adequate level of protection for an uninfected individual or prevent onward transmission from an infected individual (source control). Hand hygiene, physical distancing of at least 1 metre, respiratory etiquette, adequate ventilation in indoor settings, testing, contact tracing, quarantine, isolation and other infection prevention and control (IPC) measures are critical to prevent human-to-human transmission of SARS-CoV-2, whether or not masks are used ( 6).

Mask management

For any type of mask, appropriate use, storage and cleaning, or disposal are essential to ensure that they are as effective as possible and to avoid any increased risk of transmission. Adherence to correct mask management practices varies, reinforcing the need for appropriate messaging (7).

WHO provides the following guidance on the correct use of masks:

• Perform hand hygiene before putting on the mask. • Inspect the mask for tears or holes, and do not use a

damaged mask. • Place the mask carefully, ensuring it covers the mouth

and nose, adjust to the nose bridge and tie it securely to minimize any gaps between the face and the mask. If using ear loops, ensure these do not cross over as this widens the gap between the face and the mask.

• Avoid touching the mask while wearing it. If the mask is accidently touched, perform hand hygiene.

• Remove the mask using the appropriate technique. Do not touch the front of the mask, but rather untie it from behind.

• Replace the mask as soon as it becomes damp with a new clean, dry mask.

• Either discard the mask or place it in a clean plastic resealable bag where it is kept until it can be washed and cleaned. Do not store the mask around the arm or wrist or pull it down to rest around the chin or neck.

• Perform hand hygiene immediately afterward discarding a mask.

• Do not re-use single-use mask. • Discard single-use masks after each use and properly

dispose of them immediately upon removal. • Do not remove the mask to speak. • Do not share your mask with others. • Wash fabric masks in soap or detergent and preferably

hot water (at least 60° Centigrade/140° Fahrenheit) at least once a day. If it is not possible to wash the masks in hot water, then wash the mask in soap/detergent and room temperature water, followed by boiling the mask for 1 minute.

Scientific evidence

Transmission of the SARS-CoV-2 virus

Knowledge about transmission of the SARS-CoV-2 virus is evolving continuously as new evidence accumulates. COVID-19 is primarily a respiratory disease, and the clinical spectrum can range from no symptoms to severe acute respiratory illness, sepsis with organ dysfunction and death.

According to available evidence, SARS-Co V-2 mainly spreads between people when an infected person is in close contact with another person. Transmissibility of the virus depends on the amount of viable virus being shed and expelled by a person, the type of contact they have with others, the setting and what IPC measures are in place. The virus can spread from an infected person's mouth or nose in small liquid particles when the person coughs, sneezes, sings, breathes heavily or talks. These liquid particles are different sizes, ranging from larger 'respiratory droplets' to smaller 'aerosols.' Close-range contact (typically within 1 metre) can result in inhalation of, or inoculation with, the virus through the mouth, nose or eyes (8-13).

There is limited evidence of transmission through fomites ( objects or materials that may be contaminated with viable virus, such as utensils and furniture or in health care settings a stethoscope or thermometer) in the immediate environment around the infected person ( 14-17). Nonetheless, fomite transmission is considered a possible mode of transmission for SARS-Co V-2, given consistent finding of environmental contamination in the vicinity of people infected with SARSCo V-2 and the fact that other coronaviruses and respiratory viruses can be transmitted this way ( 12).

Aerosol transmission can occur in specific situations in which procedures that generate aerosols are performed. The scientific community has been actively researching whether the SARS-CoV-2 virus might also spread through aerosol transmission in the absence of aerosol generating procedures (AGPs) (18, 19). Some studies that performed air sampling in

clinical settings where AGPs were not performed found virus RNA, but others did not. The presence of viral RNA is not the same as replication- and infection-competent (viable) virus that could be transmissible and capable of sufficient inoculum to initiate invasive infection. A limited number of studies have isolated viable SARS-CoV-2 from air samples in the vicinity of COVID-19 patients (20, 21 ).

Outside of medical facilities, in addition to droplet and fomite transmission, aerosol transmission can occur in specific settings and circumstances, particularly in indoor, crowded and inadequately ventilated spaces, where infected persons spend long periods of time with others. Studies have suggested these can include restaurants, choir practices, fitness classes, nightclubs, offices and places of worship (12).

High quality research is required to address the knowledge gaps related to modes of transmission, infectious dose and settings in which transmission can be amplified. Currently, studies are underway to better understand the conditions in which aerosol transmission or superspreading events may occur.

Current evidence suggests that people infected with SARSCo V-2 can transmit the virus whether they have symptoms or not. However, data from viral shedding studies suggest that infected individuals have highest viral loads just before or around the time they develop symptoms and during the first 5-7 days of illness (12). Among symptomatic patients, the duration of infectious virus shedding has been estimated at 8 days from the onset of symptoms (22-24) for patients with mild disease, and longer for severely ill patients ( 12). The period of infectiousness is shorter than the duration of detectable RNA shedding, which can last many weeks ( 17).

The incubation period for COVID-19, which is the time between exposure to the virus and symptom onset, is on average 5-6 days, but can be as long as 14 days (25, 26).

Pre-symptomatic transmission - from people who are infected and shedding virus but have not yet developed symptoms - can occur. Available data suggest that some people who have been exposed to the virus can test positive for SARS-CoV-2 via polymerase chain reaction (PCR) testing 1-3 days before they develop symptoms (27). People who develop symptoms appear to have high viral loads on or just prior to the day of symptom onset, relative to later on in their infection (28).

Asymptomatic transmission - transmission from people infected with SARS-Co V-2 who never develop symptoms -can occur. One systematic review of 79 studies found that 20% (17-25%) of people remained asymptomatic throughout the course of infection. (28). Another systematic review, which included 13 studies considered to be at low risk of bias, estimated that 17% of cases remain asymptomatic (14%-20%) (30). Viable virus has been isolated from specimens of presymptomatic and asymptomatic individuals, suggesting that people who do not have symptoms may be able to transmit the virus to others. (25, 29-37)

Studies suggest that asymptomatically infected individuals are less likely to transmit the virus than those who develop symptoms (29). A systematic review concluded that individuals who are asymptomatic are responsible for transmitting fewer infections than symptomatic and presymptomatic cases (38). One meta-analysis estimated that there is a 42% lower relative risk of asymptomatic transmission compared to symptomatic transmission (30).

Guidance on mask use in health care settings

Masks for use in health care settings

Medical masks are defined as surgical or procedure masks that are flat or pleated. They are affixed to the head with straps that go around the ears or head or both. Their performance characteristics are tested according to a set of standardized test methods (ASTM F2100, EN 14683, or equivalent) that aim to balance high filtration, adequate breathability and optionally, fluid penetration resistance (39, 40).

Filteringfacepiece respirators (FFR), or respirators, offer a balance of filtration and breathability. However, whereas medical masks filter 3 micrometre droplets, respirators must filter more challenging 0.075 micrometre solid particles. European FFRs, according to standard EN 149, at FFP2 performance there is filtration of at least 94% solid NaCl particles and oil droplets. US N95 FFRs, according to NIOSH 42 CFR Part 84, filter at least 95% NaCl particles. Certified FFRs must also ensure unhindered breathing with maximum resistance during inhalation and exhalation. Another important difference between FFRs and other masks is the way filtration is tested. Medical mask filtration tests are performed on a cross-section of the masks, whereas FFRs are tested for filtration across the entire surface. Therefore, the layers of the filtration material and the FFR shape, which ensure the outer edges of the FFR seal around wearer's face, result in guaranteed filtration as claimed. Medical masks, by contrast, have an open shape and potentially leaking structure. Other FFR performance requirements include being within specified parameters for maximum CO2 build up, total inward leakage and tensile strength of straps (41, 42).

A. Guidance on the use of medical masks and respirators to provide care to suspected or confirmed COVID-19 cases

Evidence on the use of mask in health care settings

Systematic reviews have reported that the use of N95/P2 respirators compared with the use of medical masks (see mask definitions, above) is not associated with statistically significant differences for the outcomes of health workers acquiring clinical respiratory illness, influenza-like illness (risk ratio 0.83, 95%CI 0.63-1.08) or laboratory-confirmed influenza (risk ratio 1.02, 95%CI 0. 73-1.43); harms were poorly reported and limited to discom~ort associate~ with lower compliance (43, 44). In many settmgs, preserving the supply of N95 respirators for high-risk, aerosol-generating procedures is an important consideration ( 45).

A systematic review of observational studies ~n the betacoronaviruses that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and COVID-19 found that the use of face protection (including respirators and medical masks) is associated with reduced risk of infection among health workers. These studies suggested that N95 or similar respirators might be associated with greater reduction in risk than medical or 12-16-layer cotton masks. However, these studies had important

2 The WHO list of AGPs includes tracheal intubation, non-invasive ventilation, tracheotomy, cardiopulmonary resuscitation, manual

limitations (recall bias, limited information about the situations when respirators were used and limited ability to measure exposures), and very few studies included in the review evaluated the transmission risk of COVID-19 ( 46). Most of the studies were conducted in settings in which AGPs were performed or other high-risk settings ( e.g., intensive care units or where there was exposure to infected patients and health workers were not wearing adequate PPE).

WHO continues to evaluate the evidence on the effectiveness of the use of different masks and their potential harms, risks and disadvantages, as well as their combination with hand hygiene, physical distancing of at least 1 metre and other IPC measures.

Guidance

WHO's guidance on the type of respiratory protection to be worn by health workers providing care to COVID-19 patients is based on 1) WHO recommendations on IPC for epidemicand pandemic-prone acute respiratory infections in health care (47); 2) updated systematic reviews of randomized controlled trials on the effectiveness of medical masks compared to that ofrespirators for reducing the risk of clinical respiratory illness, influenza-like illness (ILi) and laboratoryconfirmed influenza or viral infections. WHO guidance in this area is aligned with guidelines of other professional organizations, including the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, and the Infectious Diseases Society of America ( 48, 49). ·

The WHO COVID-19 IPC GOG considered all available evidence on the modes of transmission of SARS-Co V-2 and on the effectiveness of medical mask versus respirator use to protect health workers from infection and the potential for harms such as skin conditions or breathing difficulties.

Other considerations included availability of medical masks versus respirators, cost and procurement implications and equity of access by health workers across different settings.

The majority (71%) of the GOG members confirmed their support for previous recommendations issued by WHO on 5 June 2020: 1. In the absence of aerosol generating procedures (AGPs) 2,

WHO recommends that health workers providing care to patients with suspected or confirmed COVID-19 should wear a medical mask (in addition to other PPE that are part of droplet and contact precautions).

2. In care settings for COVID-19 patients where AGPs are performed, WHO recommends that health workers should wear a respirator (N95 or FFP2 or FFP3 standard, or equivalent) in ·addition to other PPE that are part of airborne and contact precautions.

In general, health workers have strong preferences about having the highest perceived protection possible to prevent COVID-19 infection and therefore may place high value on the potential benefits of respirators in settings without AGPs. WHO recommends respirators primarily for settings where AGPs are performed; however, if health workers prefer them and they are sufficiently available and cost is not ~ issu~, they could also be used during care for COVID~ 19 pa!1ents m other settings. For additional guidance on PPE, mcludmg PPE

ventilation before intubation, bronchoscopy, sputum induction using nebulized hypertonic saline, and dentistry and autopsy procedures.

beyond mask use by health workers, see WHO IPC guidance during health care when COVID-19 infection is suspected (3) and also WHO guidance on the rational use of PPE ( 45).

Exhalation valves on respirators are discouraged as they bypass the filtration function for exhaled air.

B. Guidance on the use of mask by health workers, caregivers and others based on transmission scenario

Definitions

Universal masking in health facilities is defined as the requirement for all persons (staff, patients, visitors, service providers and others) to wear a mask at all times except for when eating or drinking.

Targeted continuous medical mask use is defined as the practice of wearing a medical mask by all health workers and caregivers working in clinical areas during all routine activities throughout the entire shift.

Health workers are all people primarily engaged in actions with the primary intent of enhancing health. Examples are: nursing and midwifery professionals, doctors, cleaners, other staff who work in health facilities, social workers, and community health workers.

Evidence on universal masking in health care settings

In areas where there is community transmission or large-scale outbreaks of COVID-19, universal masking has been adopted in many hospitals to reduce the potential of transmission by health workers to patients, to other staff and anyone else entering the facility (50).

Two studies found that implementation of a universal masking policy in hospital systems was associated with decreased risk of healthcare-acquired SARS-Co V-2 infection. However, these studies had serious limitations: both were before-after studies describing a single example of a phenomenon before and after an event of interest, with no concurrent control group, and other infection control measures were not controlled for (51, 52). In addition, observed decreases in health worker infections occurred too quickly to be attributable to the universal masking policy.

Guidance

Although more research on universal masking in heath settings is needed, it is the expert opinion of the majority (79%) of WHO COVID-19 IPC ODO members that universal masking is advisable in geographic settings where there is known or suspected community or cluster transmission of the SARS-Co V-2 virus. 1. In areas of known or suspected community or cluster

SARS-Co V-2 transmission, universal masking should be advised in all health facilities (see Table 1 ).

• All health workers, including community health workers and caregivers, should wear a medical mask at all times, for any activity ( care of COVID-19 or nonCOVID-19 patients) and in any common area (e.g., cafeteria, staff rooms).

• Other staff, visitors, outpatients and service providers should also wear a mask (medical or non-medical) at all times

• Inpatients are not required to wear a mask (medical or non-medical) unless physical distancing of at least 1 metre cannot be maintained ( e.g., when being examined or visited at the bedside) or when outside of their care area ( e.g., when being transported).

• Masks should be changed when they become soiled, wet or damaged or if the health worker/caregiver removes the mask ( e.g., for eating or drinking or caring for a patient who requires droplet/contact precautions for reasons other than COVID-19).

2. In the context of known or suspected sporadic SARSCo V-2 virus transmission, WHO provides the following guidance:

• Health workers, including community health workers and caregivers who work in clinical areas, should continuously wear a medical mask during routine activities throughout the entire shift, apart from when eating and drinking and changing their medical masks after caring for a patient who requires droplet/contact precautions for other reasons. In all cases, medical masks must be changed when wet, soiled, or damaged; used medical masks should be properly disposed of at the end of the shift; and new clean ones should be used for the next shift or when medical masks are changed.

• It is particularly important to adopt the continuous use of masks in potentially high transmission risk settings including triage, family physician/general practitioner offices; outpatient departments; emergency rooms; COVID-19 designated units; haematology, oncology and transplant units; and long-term health and residential facilities.

• Staff who do not work in clinical areas ( e.g., administrative staff) do not need to wear a medical mask during routine activities if they have no exposure to patients.

Whether using masks for universal masking within health facilities or targeted continuous medical mask use throughout the entire shift, health workers should ensure the following:

• Medical mask use should be combined with other measures including frequent hand hygiene and physical distancing among health workers in shared and crowded places such as cafeterias, break rooms, and dressing rooms.

• The medical mask should be changed when wet, soiled, or damaged.

• The medical mask should not be touched to adjust it or if displaced from the face for any reason. If this happens, the mask should be safely removed and replaced, and hand hygiene performed.

• The medical mask ( as well as other personal protective equipment) should be discarded and changed after caring for any patient who requires contact/droplet precautions for other pathogens, followed by hand hygiene.

• Under no circumstances should medical masks be shared between health workers or between others wearing them. Masks should be appropriately disposed of whenever removed and not reused.

• A particulate respirator at least as protective as a United States of America (US) National Institute for Occupational Safety and Health-certified N95, N99, US Food and Drug Administration surgical N95, European Union standard FFP2 or FFP3, or equivalent, should be worn in settings for COVID-19 patients where AGPs are performed (see WHO recommendations below). In these settings, this includes continuous use by health workers throughout the entire shift, when this policy is implemented.

Note: Decision makers may consider the transmission intensity in the catchment area of the health facility or community setting and the feasibility of implementing a universal masking policy compared to a policy based on assessed or presumed exposure risk. Decisions need to take into account procurement, sustainability and costs of the policy. When planning masks for all health workers, longterm availability of adequate medical masks ( and when applicable, respirators) for all workers should be ensured, in particular for those providing care for patients with confirmed or suspected COVID-19. Proper use and adequate waste management should be ensured.

The potential harms and risks of mask and respirator use in the health facility setting include:

• contamination of the mask due to its manipulation by contaminated hands (53, 54);

• potential self-contamination that can occur if medical masks are not changed when wet, soiled or damaged; or by frequent touching/adjusting when worn for prolonged periods (55);

• possible development of facial skin lesions, irritant dermatitis or worsening acne, when used frequently for long hours (56-58);

• discomfort, facial temperature changes and headaches from mask wearing (44, 59, 60);

• false sense of security leading potentially to reduced adherence to well recognized preventive measures such as physical distancing and hand hygiene; and risk-taking behaviours ( 61-64 );

• difficulty wearing a mask in hot and humid environments • possible risk of stock depletion due to widespread use in

the context of universal masking and targeted continuous mask use and consequent scarcity or unavailability for health workers caring for COVID 19 patients and during health care interactions with non-COVID-19 patients where medical masks or respirators might be required.

Alternatives to medical masks in health care settings

The WHO's disease commodity package (DCP) for COVID-19 recommends medical masks for health workers to be type II or higher ( 65). Type II medical masks provide a physical barrier to fluids and particulate materials and have bacterial filtration efficiency of ~98% compared to Type I mask, which has bacterial filtration efficiency of ~95% and lower fluid resistance ( 66) In case of stock outs of type II or higher medical masks, health workers should use a type I medical mask as an alternative. Other alternatives such as face shields or fabric masks should be carefully evaluated.

Face shields are designed to provide protection from splashes of biological fluid (particularly respiratory secretions), chemica1 agents and debris ( 67, 68) into the eyes. In the context of protection from SARS-Co V-2 transmission through respiratory droplets, face shields are used by health workers as personal protective equipment (PPE) for eye protection in combination with a medical mask or a respirator (69, 70) While a face shield may confer partial protection of the facial area against respiratory droplets, these and smaller droplets may come into contact with mucous membranes or with the eyes from the open gaps between the visor and the face (71,67).

Fabric masks are not regulated as protective masks or part of the PPE directive. They vary in quality and are not subject to mandatory testing or common standards and as such are not considered an appropriate alternative to medical masks for protection of health workers. One study that evaluated the use of cloth masks in a health care facility found that health care workers using 2 ply cotton cloth masks (a type of fabric mask) were at increased risk of influenza-like illness compared with those who wore medical masks (72).

In the context of severe medical mask shortage, face shields alone or in combination with fabric mask may be considered as a last resort (73). Ensure proper design of face shields to cover the sides of the face and below the chin.

As for other PPE items, if production of fabric masks for use in health care settings is proposed locally in situations of shortage or stock out, a local authority should assess the product according to specific minimum performance standards and required technical specifications (see Annex).

Additional considerations for community care settings

Like other health workers, community health workers should apply standard precautions for all patients at all times, with particular emphasis regarding hand and respiratory hygiene, surface and environmental cleaning and disinfection and the appropriate use of PPE. When a patient is suspected or confirmed of having COVID-19, community health workers should always apply contact and droplet precautions. These include the use of a medical mask, gown, gloves and eye protection (7 4 ).

IPC measures that are needed will depend on the local COVID-19 transmission dynamics and the type of contact required by the health care activity (see Table I). The community health workforce should ensure that patients and workforce members apply precautionary measures such as respiratory hygiene and physical distancing of at least 1 metre (3.3 feet). They also may support set-up and maintenance of hand hygiene stations and community education (74). In the context of known or suspected community or cluster transmission, community health workers should wear a medical mask when providing essential routine services (see Table 1).

Table 1. Mask use in health care settings depending on transmission scenario, target population, setting, activity and type*

Transmission Target population Setting (where) Activity (what) Mask type (which scenario (who) one)*

Known or Health workers and Health facility For any activity in patient-care Medical mask ( or suspected caregivers (including primary, areas (COVID-19 or non- respirator if aerosol community or secondary, tertiary care COVID-19 patients) or in any generating cluster levels, outpatient care, common areas ( e.g., cafeteria, procedures transmission and long-term care staff rooms) performed) ofSARS- Other staff, patients, facilities) For any activity or in any Medical or fabric CoV-2 visitors, service common area mask

suppliers

Inpatients In single or multiple- When physical distance of at bed rooms least 1 metre cannot be

maintained

Health workers and Home visit ( for When in direct contact with a Medical mask caregivers example, for antenatal patient or when a distance of at

or postnatal care, or for least 1 metre cannot be a chronic condition) maintained.

Community Community outreach programmes/essential routine services

Known or Health workers and Health facility In patient care area- irrespective Medical mask suspected caregivers (including primary, of whether patients have sporadic secondary, tertiary care suspected/confirmed COVID-19 transmission Other staff, patients, levels, outpatient care, No routine activities in patient Medical mask not ofSARS- visitors, service and long-term care areas required. Medical CoV-2 cases suppliers and all others facilities) mask should be

worn if in contact or within 1 metre of patients, or according to local risk assessment

Health workers and Home visit ( for When in direct contact or when a Medical mask caregivers example, for antenatal distance of at least 1 metre

or postnatal care, or for cannot be maintained. a chronic condition)

Community Community outreach programs ( e.g., bed net distribution)

No Health workers and Health facility Providing any patient care Medical mask use documented caregivers (including primary, according to SARS-CoV-2 secondary, tertiary care standard and transmission levels, outpatient care, transmission-based

and long-term care precautions facilities)

Community Community outreach programs

Any Health workers Health care facility Performing an AGP on a Respirator (N95 or transmission (including primary, suspected or confirmed COVID- N99 or FFP2 or scenario secondary, tertiary care 19 patient or providing care in a FFP3)

levels, outpatient care, setting where AGPs are in place and long-term care for COVID-19 patients facilities), in settings where aerosol generating procedures (AGP) are performed

• This table refers only to the use of medical masks and respirators. The use of medical masks and respirators may need to be combined with other personal protective equipment and other measures as appropriate, and always with hand hygiene.

Guidance on mask use in community settings

Evidence on the protective effect of mask use in community settings

At present there is only limited and inconsistent scientific evidence to support the effectiveness of masking of healthy people in the community to prevent infection with respiratory viruses, including SARS-CoV-2 (75). A large randomized community-based trial in which 4862 healthy participants were divided into a group wearing medical/surgical masks and a control group found no difference in infection with SARS-CoV-2 (76). A recent systematic review found nine trials ( of which eight were cluster-randomized controlled trials in which clusters of people, versus individuals, were randomized) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness. Two trials were with healthcare workers and seven in the community. The review concluded that wearing a mask may make little or no difference to the prevention of influenza-like illness (ILi) (RR 0.99, 95%CI 0.82 to 1.18) or laboratory confirmed illness (LCI) (RR 0.91, 95%CI 0.66-1.26) (44); the certainty of the evidence was low for ILi, moderate for LCI.

By contrast, a small retrospective cohort study from Beijing found that mask use by entire families before the first family member developed COVID-19 symptoms was 79% effective in reducing transmission (OR 0.21, 0.06-0.79) (77). A casecontrol study from Thailand found that wearing a medical or non-medical mask all the time during contact with a COVID-19 patient was associated with a 77% lower risk of infection (aOR 0.23; 95% CI 0.09-0.60) (78). Several small observational studies with epidemiological data have reported an association between mask use by an infected person and prevention of onward transmission of SARSCo V-2 infection in public settings. (8, 79-81).

A number of studies, some peer reviewed (82-86) but most published as pre-prints (87-104), reported a decline in the COVID-19 cases associated with face mask usage by the public, using country- or region-level data. One study reported an association between community mask wearing policy adoption and increased movement (less time at home, increased visits to commercial locations) (105). These studies differed in setting, data sources and statistical methods and have important limitations to consider (106), notably the lack of information about actual exposure risk among individuals, adherence to mask wearing and the enforcement of other preventive measures (107, 108).

Studies of influenza, influenza-like illness and human coronaviruses (not including COVID-19) provide evidence that the use of a medical mask can prevent the spread of infectious droplets from a symptomatic infected person to someone else and potential contamination of the environment by these droplets (75). There is limited evidence that wearing a medical mask may be beneficial for preventing transmission between healthy individuals sharing households with a sick person or among attendees of mass gatherings (44, 109-114).

3 For adequate ventilation refer to regional or national institutions or heating, refrigerating and air-conditioning societies enacting ventilation requirements. If not available or applicable, a recommended ventilation rate of IO Vs/person should be met (except healthcare facilities which have specific requirements). For more information consult "Coronavirus (COVID-19) response

A meta-analysis of observational studies on infections due to betacoronaviruses, with the intrinsic biases of observational data, showed that the use of either disposable medical masks or reusable 12-16-layer cotton masks was associated with protection of healthy individuals within households and among contacts of cases ( 46). This could be considered to be indirect evidence for the use of masks (medical or other) by healthy individuals in the wider community; however, these studies suggest that such individuals would need to be in close proximity to an infected person in a household or at a mass gathering where physical distancing cannot be achieved to become infected with the virus. Results from cluster randomized controlled trials on the use of masks among young adults living in university residences in the United States of America indicate that face masks may reduce the rate of influenza-like illness but showed no impact on risk of laboratory-confirmed influenza (115, 116).

Guidance

The WHO COVID-19 IPC GOG considered all available evidence on the use of masks by the general public including effectiveness, level of certainty and other potential benefits and harms, with respect to transmission scenarios, indoor versus outdoor settings, physical distancing and ventilation. Despite the limited evidence of protective efficacy of mask wearing in community settings, in addition to all other recommended preventive measures, the GOG advised mask wearing in the following settings:

1. In areas with known or suspected community or cluster transmission of SARS-Co V-2, WHO advises mask use by the public in the following situations (see Table 2):

Indoor settings: - in public indoor settings where ventilation is known to be

poor regardless of physical distancing: limited or no opening of windows and doors for natural ventilation; ventilation system is not properly functioning or maintained; or cannot be assessed;

- in public indoor settings that have adequate3 ventilation if physical distancing of at least 1 metre cannot be maintained;

- in household indoor settings: when there is a visitor who is not a household member and ventilation is known to be poor, with limited opening of windows and doors for natural ventilation, or the ventilation system cannot be assessed or is not properly functioning, regardless of whether physical distancing of at least 1 metre can be maintained;

- in household indoor settings that have adequate ventilation if physical distancing of at least 1 metre cannot be maintained.

resources from ASHRAE and others'' https://wv.·w.ashrae.org/technical-resources/resources

Table 2. Mask use in community settings depending on transmission scenario, setting, target population, purpose and type*

Transmission scenario

Situations/settings (where) Target Population (who)

Known or suspected Indoor settings, where community or ventilation is known to be cluster transmission poor or cannot be assessed or of SARS-Co V-2 the ventilation system is not

General population in public* settings such as shops, shared workplaces, schools, churches, restaurants, gyms, etc. or in enclosed settings such as public transportation. properly maintained,

regardless of whether

physical distancing of at least For households, in indoor settings, when _1 _m_e_t_er_can_b_e_m_a_in_t_a_in_e_d ___ there is a visitor who is not a member of

Indoor settings that have the household adequate 4 ventilation if physical distancing of at least 1 metre cannot be maintained

Outdoor settings where General population in settings such as physical distancing cannot be crowded open-air markets, lining up maintained outside a building, during

demonstrations, etc.

Purpose of mask use

(why)

Potential benefit for source control

Settings where physical Individuals/people with higher risk of Protection

Known or suspected sporadic transmission, or no documented SARSCo V-2 transmission

distancing cannot be severe complications from COVID-19: maintained, and the individual • People aged ~60 years is at increased risk of infection and/or negative outcomes

Risk-based approach

• People with underlying comorbidities, such as cardiovascular disease or diabetes mellitus, chronic lung disease, cancer, cerebrovascular disease, immunosuppression, obesity, asthma

General population Potential benefit for source control and/or protection

Any transmission Any setting in the community Anyone suspected or confirmed of Source scenario having COVID-19, regardless of control

whether they have symptoms or not, or anyone awaiting viral test results, when in the presence of others

• Public indoor setting includes any indoor setting outside of the household

Mask type (which one)

Fabric mask

Medical mask

Depends on purpose (see details in the guidance content)

Medical mask

4 For adequate ventilation refer to regional or national institutions or heating, refrigerating and air-conditioning societies enacting ventilation requirements. Ifnot available or applicable, a recommended ventilation rate of 101/s/person should be met (except healthcare facilities which have specific requirements).). For more information consult "Coronavirus (COVID-19) response resources from ASHRAE and others" https://www.ashrae.org/technical-resources/resources

In outdoor settings: - where physical distancing of at least l metre cannot be

maintained;

individuals/people with higher risk of severe complications from COVID-19 (individuals~ 60 years old and those with underlying conditions such as cardiovascular disease or diabetes mellitus, chronic lung disease, cancer, cerebrovascular disease or immunosuppression) should wear medical masks in any setting where physical distance cannot be maintained.

· 2. In areas with known or suspected sporadic transmission or no documented transmission, as in all transmission scenarios, WHO continues to advise that decision makers should apply a risk-based approach focusing on the following criteria when considering the use of masks for the public: • Purpose of mask use. Is the intention source control

(preventing an infected person from transmitting the virus to others) or protection (preventing a healthy wearer from the infection)?

• Risk of exposure to SARS-Co V-2. Based on the epidemiology and intensity of transmission in the population, is there transmission and limited or no capacity to implement other containment measures such as contact tracing, ability to carry out testing and isolate and care for suspected and confirmed cases? Is there risk to individuals working in close contact with the public ( e.g., social workers, personal support workers, teachers, cashiers)?

• Vulnerability of the mask wearer/population. Is the mask wearer at risk of severe complications from COVID-19? Medical masks should be used by older people (2: 60 years old), immunocompromised patients and people with comorbidities, such as cardiovascular disease or diabetes mellitus, chronic lung disease, cancer and cerebrovascular disease ( 11 7).

• Setting in which the population lives. Is there high population density (such as in refugee camps, camp-like settings, and among people living in cramped conditions) and settings where individuals are unable to keep a physical distance of at least 1 metre (for example, on public transportation)?

• Feasibility. Are masks available at an affordable cost? Do people have access to clean water to wash fabric masks, and can the targeted population tolerate possible adverse effects of wearing a mask?

• Type of mask. Does the use of medical masks in the community divert this critical resource from the health workers and others who need them the most? In settings where medical masks are in short supply, stocks should be prioritized for health workers and at-risk individuals.

The decision of governments and local jurisdictions whether to recommend or make mandatory the use of masks should be based on the above assessment as well as the local context, culture, availability of masks and resources required.

3. In any transmission scenario: • Persons with any symptoms suggestive of COVID-19

should wear a medical mask and (5) additionally: - self-isolate and seek medical advice as soon as they

start to feel unwell with potential symptoms of COVID-19, even if symptoms are mild);

- follow instructions on how to put on, take off, and dispose of medical masks and perform hand hygiene (118);

- follow all additional measures, in particular respiratory hygiene, frequent hand hygiene and maintaining physical distance of at least 1 metre from other persons ( 46). If a medical mask is not available for individuals with suspected or confirmed COVID-19, a fabric mask meeting the specifications in the Annex of this document should be worn by patients as a source control measure, pending access to a medical mask. The use of a nonmedical mask can minimize the projection of respiratory droplets from the user (I I 9, 120).

- Asymptomatic persons who test positive for SARSCo V-2, should wear a medical mask when with others for a period of IO days after testing positive.

Potential benefits/harms

The potential advantages of mask use by healthy people in the general public include: • reduced spread of respiratory droplets containing

infectious viral particles, including from infected persons before they develop symptoms ( 121 );

• reduced potential for stigmatization and greater of acceptance of mask wearing, whether to prevent infecting others or by people caring for COVID-19 patients in non-clinical settings (122);

• making people feel they can play a role in contributing to stopping spread of the virus;

• encouraging concurrent transmission prevention behaviours such as hand hygiene and not touching the eyes, nose and mouth (123-125);

• preventing transmission of other respiratory illnesses like tuberculosis and influenza and reducing the burden of those diseases during the pandemic ( 126).

The potential disadvantages of mask use by healthy people in the general public include: • headache and/or breathing difficulties, depending on

type of mask used (55); • development of facial skin lesions, irritant dermatitis or

worsening acne, when used frequently for long hours (58, 59, 127);

• difficulty with communicating clearly, especially for persons who are deaf or have poor hearing or use lip reading (128, 129);

• discomfort ( 44, 55, 59) • a false sense of security leading to potentially lower

adherence to other critical preventive measures such as physical distancing and hand hygiene ( 105);

• poor compliance with mask wearing, in particular by young children (111, 130-132);

• waste management issues; improper mask disposal leading to increased litter in public places and environmental hazards (133);

• disadvantages for or difficulty wearing masks, especially for children, developmentally challenged persons, those with mental illness, persons with cognitive impairment, those with asthma or chronic respiratory or breathing problems, those who have had facial trauma or recent oral maxillofacial surgery and those living in hot and humid environments (55, 130).

Considerations for implementation

When implementing mask policies for the public, decisionmakers should: • clearly communicate the purpose of wearing a mask,

including when, where, how and what type of mask should be worn; explain what wearing a mask may achieve and what it will not achieve; and communicate clearly that this is one part of a package of measures along with hand hygiene, physical distancing, respiratory etiquette, adequate ventilation in indoor settings and other measures that are all necessary and all reinforce each other;

• inform/train people on when and how to use masks appropriately and safely (see mask management and maintenance sections);

• consider the feasibility of use, supply/access issues ( cleaning, storage), waste management, sustainability, social and psychological acceptance ( of both wearing and not wearing different types of masks in different contexts);

• continue gathering scientific data and evidence on the effectiveness of mask use (including different types of masks) in non-health care settings;

• evaluate the impact (positive, neutral or negative) of using masks in the general population (including behavioural and social sciences) through good quality research.

Mask use during physical activity

Evidence

There are limited studies on the benefits and harms of wearing medical masks, respirators and non-medical masks while exercising. Several studies have demonstrated statistically significant deleterious effects on various cardiopulmonary physiologic parameters during mild to moderate exercise in healthy subjects and in those with underlying respiratory diseases ( 134-140). The most significant impacts have been consistently associated with the use of respirators and in persons with underlying obstructive airway pulmonary diseases such as asthma and chronic obstructive pulmonary disease (COPD), especially when the condition is moderate to severe (136). Facial microclimate changes with increased temperature, humidity and perceptions of dyspnoea were also reported in some studies on the use of masks during exercise ( 134, 141 ). A recent review found negligeable evidence of negative effects of mask use during exercise but noted concern for individuals with severe cardiopulmonary disease (142).

Guidance

WHO advises that people should not wear masks during vigorous intensity physical activity (143) because masks may reduce the ability to breathe comfortably. The most important preventive measure is to maintain physical distancing of at least 1 meter and ensure good ventilation when exercising.

If the activity takes place indoors, adequate ventilation should be ensured at all times through natural ventilation or a properly functioning or maintained ventilation system (144). Particular attention should be paid to cleaning and disinfection of the environment, especially high-touch surfaces. If all the above measures cannot be ensured, consider temporary closure of public indoor exercise facilities ( e.g., gyms).

Face shields for the general public

At present, face shields are considered to provide a level of eye protection only and should not be considered as an equivalent to masks with respect to respiratory droplet protection and/or source control. Current laboratory testing standards only assess face shields for their ability to provide eye protection from chemical splashes ( 145).

In the context of non-availability or difficulties wearing a non-medical mask (in persons with cognitive, respiratory or hearing impairments, for example), face shields may be considered as an alternative, noting that they are inferior to masks with respect to droplet transmission and prevention. If face shields are to be used, ensure proper design to cover the sides of the face and below the chin.

Medical masks for the care of COVID-19 patients at home

WHO provides guidance on how to care for patients with confirmed and suspected COVID-19 at home when care in a health facility or other residential setting is not possible (5).

Persons with suspected COVID-19 or mild COVID-19 symptoms should wear a medical mask as much as possible, especially when there is no alternative to being in the same room with other people. The mask should be changed at least once daily. Persons who cannot tolerate a medical mask should rigorously apply respiratory hygiene (i.e., cover mouth and nose with a disposable paper tissue when coughing or sneezing and dispose of it immediately after use or use a bent elbow procedure and then perform hand hygiene). Caregivers of or those sharing living space with people with suspected COVID-19 or with mild COVID-19 symptoms should wear a medical mask when in the same room as the affected person.

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Acknowledgments

This document was developed based on advice by the Strategic and Technical Advisory Grou~ for Infecti~us Hazards (STAG-IH), and in consultation with the followmg members of:

1) The WHO Health Emergencies Programme (WHE) Adhoc COVID-19 IPC Guidance Development Group (in alphabetical order):

Jameela Alsalman, Ministry of Health, Bahrain; ~ucha Apisamthanarak, Thammsat University Hospital, Thatland; Baba Aye, Public Services International~ France; Gregory Built, UNICEF, United States of Amenca (USA); Roger Chou, Oregon Health Science University, USA; May Chu,

Colorado School of Public Health, USA; John Conly, Alberta Health Services, Canada; Barry Cookson, University College London, United Kingdom (U.K); Nizam Damani, Southern Health & Social Care Trust, United Kingdom; Dale Fisher, GOARN, Singapore; Joost Hopman, Radboud University Medical Center, The Netherlands; Mushtuq Husain, Institute of Epidemiology, Disease Control & Research, Bangladesh; Kushlani Jayatilleke, Sri Jayewardenapura General Hospital, Sri Lanka; Seto Wing Jong, School of Public Health, Hong Kong SAR, China; Souha Kanj, American University of Beirut Medical Center, Lebanon; Daniele Lantagne, Tufts University, USA; Fernanda Lessa, Centers for Disease Control and Prevention, USA; Anna Levin, University of Sao Paulo, Brazil; Ling Moi Lin, Sing Health, Singapore; Caline Mattar, World Health Professions Alliance, USA; MaryLouise McLaws, University of New South Wales, Australia; Geeta Mehta, Journal of Patient Safety and Infection Control, India; Shaheen Mehtar, Infection Control Africa Network, South Africa; Ziad Memish, Ministry of Health, Saudi Arabia; Babacar Ndoye, Infection Control Africa Network, Senegal; Fernando Otaiza, Ministry of Health, Chile; Diamantis Plachouras, European Centre for Disease Prevention and Control, Sweden; Maria Clara Padoveze, School of Nursing, University of Sao Paulo, Brazil; Mathias Pletz, Jena University, Germany; Marina Salvadori, Public Health Agency of Canada, Canada; Mitchell Schwaber, Ministry of Health, Israel; Nandini Shetty, Public Health England, United Kingdom; Mark Sobsey, University of North Carolina, USA; Paul Ananth Tambyah, National University Hospital, Singapore; Andreas Voss, Canisus-Wilhelmina Ziekenhuis, The Netherlands; Walter Zingg, University of Geneva Hospitals, Switzerland;

2) The WHO Technical Advisory Group of Experts on Personal Protective Equipment (TAG PPE):

Faisal Al Shehri, Saudi Food and Drug Authority, Saudi Arabi; Selcen Ayse, Istanbul University-Cerrahpasa, Turkey; Razan Asally, Saudi Food and Drug Authority, Saudi Arabi; Kelly Catlin, Clinton Health Access Initiative; Patricia Ching, WHO Collaborating Center, The University of Hong Kong, China; Mark Croes, Centexbel, Spring Gombe, United Nations; Emilio Homsey, UK Public Health Rapid Support Team, U.K.; Selcen Kilinc-Balci, United States Centers for

Disease Control and Prevention (CDC), USA; Melissa Leavitt, Clinton Health Access Initiative; John McGhie, International Medical Corps; Claudio Meirovich, Meirovich Consulting; Mike Paddock, UNDP, Trish Perl, University of Texas Southwestern Medical Center, USA; Alain Prat, Global Fund, Ana Maria Rule, Johns Hopkins Bloomberg School of Public Health, U .S.A; Jitendar Sharma, Andra Pradesh MedTEch Zone, India; Alison Syrett, SIGMA, Reiner Voelksen, VOELKSEN Regulatory Affairs, Nasri Yussuf, IPC Kenya.

3) External IPC peer review group:

Paul Hunter, University of East Anglia, U .K; Direk Limmathurotsakul, Mahidol University, Thailand; Mark Loeb, Department of Pathology and Molecular Medicine, McMaster University, Canada; Kalisavar Marimuthu, National Centre for Infectious Diseases, Singapore; Yong Loo Lin School of Medicine, National University of Singapore; Nandi Siegfried, South African Medical Research Council, South Africa.

4) UNICEF observers: Nagwa Hasanin, Sarah Karmin, Raoul Kamadjeu, Jerome Pfaffmann,

WHO Secretariat:

Benedetta Allegranzi, Gertrude Avortri, Mekdim Ayana, Hanan Balkhy, April Baller, Elizabeth Barrera-Cancedda, Anjana Bhushan, Whitney Blanco, Sylvie Briand, Alessandro Cassini, Giorgio Cometto, Ana Paula Coutinho Rehse, Carmem Da Silva, Nino Dal Dayanguirang, Sophie Harriet Dennis, Sergey Eremin, Luca Fontana, Dennis Falzon, Nathan Ford, Nina Gobat, Jonas Gonseth-Garcia, Rebeca Grant, Tom Grein, Ivan Ivanov, Landry Kabego, Catherine Kane, Pierre Claver Kariyo, Ying Ling Lin, Omelia Lincetto, Abdi Mahamud, Madison Moon, Takeshi Nishijima, Kevin Babila Ousman, Pillar Ramon-Pardo, Paul Rogers, Nahoko Shindo, Alice Simniceanu, Valeska Stempliuk, Maha Talaat Ismail, Joao Paulo Toledo, Anthony Twywan, Maria Van Kerkhove, Adriana Velazquez, Vicky Willet, Masahiro Zakoji, Bassim Zayed.

WHO continues to monitor the situation closely for any changes that may affect this interim guidance. Should any factors change, WHO will issue a further update. Otherwise, this interim guidance document will expire 1 year after the date of publication.

Annex: Updated guidance on non-medical (fabric) masks

Background

A non-medical mask, also called fabric mask, community mask or face covering, is neither a medical device nor personal protective equipment. Non-medical masks are aimed at the general population, primarily for protecting others from exhaled virus-containing droplets emitted by the mask wearer. They are not regulated by local health authorities or occupational health associations, nor is it required for manufacturers to comply with guidelines established by standards organizations. Non-medical masks may be homemade or manufactured. The essential performance parameters include good breathability, filtration of droplets originating from the wearer, and a snug fit covering the nose and mouth. Exhalation valves on masks are discouraged as they bypass the filtration function of the mask.

Non-medical masks are made from a variety of woven and nonwoven fabrics, such as woven cotton, cotton/synthetic blends, polyesters and breathable spun bond polypropylene, for example. They may be made of different combinations of fabrics, layering sequences and available in diverse shapes. Currently, more is known about common household fabrics and combinations to make non-medical masks with target filtration efficiency and breathability (119, 146-150). Few of these fabrics and combinations have been systematically evaluated and there is no single design, choice of material, layering or shape among available non-medical masks that are considered optimal. While studies have focussed on single fabrics and combinations, few have looked at the shape and universal fit to the wearer. The unlimited combination of available fabrics and materials results in variable filtration and breathability.

In the context of the global shortage of medical masks and PPE, encouraging the public to create their own fabric masks may promote individual enterprise and community integration. Moreover, the production of non-medical masks may offer a source of income for those able to manufacture masks within their communities. Fabric masks can also be a form of cultural expression, encouraging public acceptance of protection measures in general. The safe re-use of fabric masks will also reduce costs and waste and contribute to sustainability (151-156).

This Annex is destined intended for two types of readers: homemade mask makers and factory-made masks manufacturers. Decision makers and managers (national/subnational level) advising on a type of non-medical mask are also the focus of this guidance and should take into consideration the following features of non-medical masks: breathability, filtration efficiency (FE), or filtration, number and combination of fabric layers material used, shape, coating and maintenance.

Evidence on the effectiveness of non-medical (fabric) masks

A number of reviews have been identified on the effectiveness of non-medical masks ( 151-156). One systematic review (155) identified 12 studies and evaluated study quality. Ten were laboratory studies (157-166), and two reports were from a single randomized trial (72, 167). The majority of studies were conducted before COVID-19 emerged or used laboratory generated particles to assess filtration efficacy. Overall, the reviews concluded that

cloth face masks have limited efficacy in combating viral infection transmission.

Homemade non-medical masks

Homemade non-medical masks made of household fabrics (e.g., cotton, cotton blends and polyesters) should ideally have a three-layer structure, with each layer providing a function (see Figure I) ( 168). It should include:

1. an innermost layer (that will be in contact with the face) of a hydrophilic material ( e.g., cotton or cotton blends of terry cloth towel, quilting cotton and flannel) that is nonirritating against the skin and can contain droplets ( 148)

2. a middle hydrophobic layer of synthetic breathable nonwoven material (spunbond polypropylene, polyester and polyaramid), which may enhance filtration, prevent permeation of droplets or retain droplets ( I 48, 150)

3. an outermost layer made of hydrophobic material (e.g. spunbond polypropylene, polyester or their blends), which may limit external contamination from penetrating through the layers to the wearer's nose and mouth and maintains and prevents water accumulation from blocking the pores of the fabric ( 148).

Although a minimum of three layers is recommended for nonmedical masks for the most common fabric used, single, double or other layer combinations of advanced materials may be used if they meet performance requirements. It is important to note that with more tightly woven materials, breathability may be reduced as the number of layers increases. A quick check may be performed by attempting to breathe, through the mouth, through the multiple layers.

- -----Inner

• Hydrophilic •Cotton or cotton blend

Outer

• Hydrophobic •Polyester

Figure I. Non-medical mask construction using breathable fabrics such as cotton, cotton blends, polyesters, nylon and polypropylene spunbond that are breathable may impart adequate filtration performance when layered. Single- or double-layer combinations of advanced materials may be used if they meet performance requirements (72).

Assumptions regarding homemade masks are that individual makers only have access to common household fabrics and do not have access to test equipment to confirm target performance (filtration and breathability). Figure I illustrates a multi-layer mask construction with examples of fabric options. Very porous materials, such as gauze, even with multiple layers, may provide very low filtration efficiency ( 14 7). Higher thread count fabrics offer improved filtration performance ( 169). Coffee filters, vacuum bags and materials not meant for clothing should be avoided as they may contain injurious content when breathed in. Microporous films such as Gore-Tex are not recommended ( 170).

Factory-made non-medical masks: general considerations for manufacturers

The non-medical mask, including all components and packaging, must be non-haz.ardous, non-toxic and childfriendly (no exposed sharp edges, protruding hardware or rough materials). Factory-made non-medical masks must be made using a process that is certified to a quality management system ( e.g., ISO 900 I). Social accountability standards ( e.g., SAI SA8000) for multiple aspects of fair labour practices, health and safety of the work force and adherence to UNICEF's Children's Rights and Business Principles are strongly encouraged.

Standards organizations' performance criteria

Manufacturers producing masks with consistent standardized performance can adhere to published, freely available guidance from several organiz.ations including those from: the French Standardization Association (AFNOR Group), The European Committee for Standardization (CEN), Swiss National COVID-19 Task Force, the American Association of Textile Chemists and Colorists (AA TCC), the South Korean Ministry of Food and Drug Safety (MFDS), the Italian Standardization Body (UNI) and the Government of Bangladesh.

Essential parameters

The essential parameters presented in this section are the synthesis of the abovementioned regional and national guidance. They include filtration, breathability and fit. Good performance is achieved when the three essential parameters are optimized at the preferred threshold (Figure 2).

Figure 2. mustration of the three essential parameters of filtration, breathability and tit.

The summary of the three essential parameters can be found in Table I and the additional performance considerations in Table 2. The minimum threshold is the minimum acceptable parameter, while the preferred threshold is the optimum.

Filtration and breathability

Filtration depends on the filtration efficiency (in%), the type of challenge particle ( oils, solids, droplets containing bacteria) and the particle size (see Table I). Depending on the fabrics used, filtration and breathability can complement or work against one another. The selection of material for droplet filtration (barrier) is as important as breathability. Filtration is dependent on the tightness of the weave, fibre or thread diameter. Non-woven materials used for disposable masks are manufactured using processes to create polymer fibres that are thinner than natural fibres such as cotton and that are held together by partial melting.

Breathability is the difference in pressure across the mask and is typically reported in millibars (mbar) or Pascals (Pa) or, normalized to the cm2 in mbar/cm2 or Pa/cm2• Acceptable breathability of a medical mask should be below 49 Pa/cm2•

For non-medical masks, an acceptable pressure difference, over the whole mask, should be below 60 Pa/cm2, with lower values indicating better breathability.

Non-medical fabric masks consisting of two layers of polypropylene spunbond and two layers of cotton have been shown to meet the minimum requirements for droplet filtration and breathability of the CEN CWA 17553 guidance. It is preferable not to select elastic material to make masks as the mask material may be stretched over the face, resulting in increased pore size and lower filtration through multiple usage. Additionally, elastic fabrics are sensitive to washing at high temperatures thus may degrade over time.

Coating the fabric with compounds like wax may increase the barrier and render the mask fluid resistant; however, such coatings may inadvertently completely block the pores and make the mask difficult to breathe through. In addition to decreased breathability unfiltered air may more likely escape the sides of the mask on exhalation. Coating is therefore not recommended.

Valves that let unfiltered air escape the mask are discouraged and are an inappropriate feature for masks used for the purpose of preventing transmission.

Table 1. Essential parameters (minimum and preferred thresholds) for manufactured non-medical mask

Essential Minimum threshold Preferred threshold Parameters

1. Filtration* 1.1. filtration

70% @ 3 micron > 70%, without compromising breathability efficiency

1.2. Challenge Solid: sodium chloride (NaCl), Talcum Based on availability particle powder, Holi powder, dolomite, Polystyrene

Latex spheres

Liquid: DEHS Di-Ethyl-Hexyl-Sebacat, paraffin oil

1.3. Particle size Choose either sizes: Range of particle sizes

3 um. 1 um. or smaller

2. Breathability

2.1. Breathing ~60 Pa/cm2 Adult: ~ 40 Pa/cm2

resistance** Paediatric: < 20 Pa/cm2

2.2 Exhalation Not recommended NIA valves

3. Fit

3.1. Coverage Full coverage of nose and mouth, consistent, Same as current requirements snug perimeter fit at the nose bridge, cheeks, chin and lateral sides of the face; adequate surface area to minimize breathing resistance and minimize side leaka2e

3.2 Face seal Not currently required Seal as good as FFR (respirator):

Fit factor of 100 for N95

Maximum Total Inward Leakage of 25% (FFPl requirement)

3.2. Sizing Adult and child Should cover from the bridge of the nose to below the chin and cheeks on either side of the mouth

Sizing for adults and children (3-5. 6-9. 10-12. >12)

3.3Strap strene:th >44.SN

• Smaller particle may result in lower filtration. •• High resistance can cause bypass of the mask. Unfiltered air will leak out the sides or around the nose if that is the easier path.

Fit: shape and sizing

Fit is the third essential parameter, and takes into consideration coverage, seal, sizing, and strap strength. Fit of masks currently is not defined by any standard except for the anthropometric considerations of facia] dimensions (ISO/TS 16976-2) or simplified to height mask (South Korean standard for KF-AD). It is important to ensure that the mask can be held in place comfortably with as little adjustment of the elastic bands or ties as possible.

Mask shapes typically include flat-fold or duckbil1 and are designed to fit closely over the nose, cheeks and chin of the wearer. Snug fitting designs are suggested as they limit leaks of unfiltered air escaping from the mask (148). Ideally the mask should not have contact with the lips, unless hydrophobic fabrics are used in at least one layer of the mask ( 148). Leaks where unfiltered air moves in and out of the mask may be attributed to the size and shape of the mask (171).

Additional considerations

Optional parameters to consider in addition to the essential performance parameters include if reusable, biodegradability for disposal masks, antimicrobial performance where applicable and chemical safety (see Table 2).

Non-medical masks intended to be reusable should include instructions for washing and must be washed a minimum of five cycles, implying initial performance is maintained after each wash cycle.

Advanced fabrics may be biodegradable or compostable at the end of service life, according to a recognized standard process ( e.g., UNI EN 13432, UNI EN 14995 and UNI / PclR 79).

Manufacturers sometimes claim their NM masks have antimicrobial performance. Antimicrobial performance may be due to coatings or additives to the fabric fibres. Treated fabrics must not come into direct contact with mucous membranes; the innermost fabric should not be treated with

antimicrobial additives, only the outermost layer. In addition, antimicrobial fabric standards (e.g., ISO 18184, ISO 20743, AATCC TMl00, AATCC 100) are general1y slow acting. The inhibition on microbial growth may take full effect after 2- or 24-hour contact time depending on the standard. The standards have generally been used for athletic apparel and substantiate claims of odour control performance. These standards are not appropriate for non-medical cloth masks and may provide a false sense of protection from infectious agents. If claims are maid, manufacturers should specify which standard supports antimicrobial performance, the challenge organism and the contact time.

Volatile additives are discouraged as these may pose a health risk when inhaled repeatedly during wear. Certification according to organizations including OEKO-TEX (Europe) or SEK (Japan), and additives complying with REACH (Europe) or the Environmental Protection Agency (EPA, United States of America) indicate that textile additives are safe and added at safe levels.

Table 2. Additional parameters for manufactured nonmedical masks

Additional parameters Minimum thresholds

If reusable, number of wash 5 cycles cvcles

Disposal Reusable

If biodegradable (CFC-BIO), according to UNI EN 13432. UNI EN 14995

Antimicrobial (bacteria, ISO 18184 (virus) virus, fungus) performance

ISO 20743 (bacteria)

ISO 13629 (fungus)

AATCC TMIO0 (bacteria)

Chemical safety Comply with REACH regulation, including inhalation safety

© World Health Organization 2020. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO licence.

WHO reference number: WHO/2019-nCo V /IPC _ Masks/2020.5

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARSCoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial . 2020 Nov 18;M20-6817. doi: 10.7326/M20-6817. Online ahead of print. Henning Bundgaard 1 , Johan Skov Bundgaard 1 , Daniel Emil Tadeusz

Raaschou-Pedersen 1 , Christian von Buchwald 2 , Tobias Todsen 2 , Jakob

Boesgaard Norsk 3 , Mia M Pries-Heje 1 , Christoffer Rasmus Vissing 1

, Pernille B Nielsen 3 , Ulrik C Winsl0w 1 , Kamille Fogh 3 , Rasmus

Hasselbalch 3 , Jonas H Kristensen 3 , Anna Ringgaard 1 , Mikkel Porsborg

Andersen 4 , Nicole Bakkegard Goecke 5 , Ramona Trebbien 6 , Kerstin

Skovgaard 7 , Thomas Benfield 8 , Henrik Ullum 2 , Christian Ton~-Pedersen 4 , KasP-er Iversen 3

Affiliations

PMID: 33205991 PMCID: PMC7707213

DOI: 10.7326LM20-6817

Free PMC article

Background: Observational evidence suggests that mask wearing

mitigates transmission of severe acute respiratory syndrome coronavirus 2

(SARS-CoV-2). It is uncertain if this observed association arises through

protection of uninfected wearers (protective effect), via reduced


transmission from infected mask wearers (source control), or both.

Objective: To assess whether recommending surgical mask use outside the

home reduces wearers' risk for SARS-CoV-2 infection in a setting where

masks were uncommon and not among recommended public health

measures.

Design: Randomized controlled trial (DANMASK-19 [Danish Study to

Assess Face Masks for the Protection Against COVID-19 Infection]).

(ClinicalTrials.gov: NCT04337541).

Setting: Denmark, April and May 2020.

Participants: Adults spending more than 3 hours per day outside the home

without occupational mask use.

Intervention: Encouragement to follow social distancing measures for

coronavirus disease 2019, plus either no mask recommendation or a

recommendation to wear a mask when outside the home among other

persons together with a supply of 50 surgical masks and instructions for

proper use.

Measurements: The primary outcome was SARS-CoV-2 infection in the

mask wearer at 1 month by antibody testing, polymerase chain reaction

(PCR), or hospital diagnosis. The secondary outcome was PCR positivity for

other respiratory viruses.

Results: A total of 3030 participants were randomly assigned to the

recommendation to wear masks, and 2994 were assigned to control; 4862

completed the study. Infection with SARS-CoV-2 occurred in 42

participants recommended masks (1.8%) and 53 control participants (2.1%).

The between-group difference was -0.3 percentage point (95% Cl, -1.2 to

0.4 percentage point; P = 0.38) (odds ratio, 0.82 [Cl, 0.54 to 1.23]; P =

0.33). Multiple imputation accounting for loss to follow-up yielded similar


results. Although the difference observed was not statistically significant,

the 95% Cls are compatible with a 46% reduction to a 23% increase in

infection.

Limitation: Inconclusive results, missing data, variable adherence, patient

reported findings on home tests, no blinding, and no assessment of

whether masks could decrease disease transmission from mask wearers to

others.

Conclusion: The recommendation to wear surgical masks to supplement

other public health measures did not reduce the SARS-CoV-2 infection rate

among wearers by more than 50% in a community with modest infection

rates, some degree of social distancing, and uncommon general mask use.

The data were compatible with lesser degrees of self-protection.

Primary funding source: The Salling Foundations.


Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China Summary box

What is already known?

• Mitigation of the COVID-19 pandemic depends solely on non

pharmaceutical interventions until drugs or vaccines are available.

Transmission of COVID-19 within families and close contacts accounts

for the majority of epidemic growth. Community mask wearing, hand

washing and social distancing are thought to be effective but the

evidence is not clear.

What are the new findings?

• The overall secondary attack rate in households was 23.0%. Face

masks were 79% effective and disinfection was 77% effective in

preventing transmission, while close frequent contact in the household

increased the risk of transmission 18 times, and diarrhoea in the index

patient increased the risk by four times. The results demonstrate the

importance of the pre-symptomatic infectiousness of COVID-19

patients and shows that wearing masks after illness onset does not

protect.

What do the new findings imply?

• The findings inform universal face mask use and social distancing, not


just in public spaces, but inside the household with members at risk of

getting infected. This further supports universal face mask use, and

also provides guidance on risk reduction for families living with

someone in quarantine or isolation, and families of health workers, who

may face ongoing risk.

Introduction

In the absence of a vaccine for COVID-19, non-pharmaceutical

interventions (NPls) are the only available disease control measures. We

have shown that population level NPls, including travel bans and the

national emergency response, were effective in flattening the COVID-19

epidemic curve in China.1 However, the effect of other NPls, such as mask

use and hygiene practices, have not been well studied in the COVID-19

pandemic.

In the USA, the use of face masks in the community has been

recommended.2 It is thought that universal face mask use (UFMU) may

reduce outward transmission from asymptomatically infected people and

protect well people from becoming infected. However, the World Health

Organization and Public Health England recommend against UFMU on the

grounds that there is little evidence from randomised controlled trials to

support this. Some experts suggest that in a pandemic, the precautionary

principle should be used and UFMU encouraged as it is unlikely to cause

harm and may result in public health gain.3 4 In countries where personal

protective equipment is scarce, people are making their own masks.

In China, over 70% of human-to-human transmission of severe acute

respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in families.5

6However, data to inform COVID-19 risk reduction in households are

unavailable. Given epidemic growth is dominated by household

transmission,5 6 studying the use of NPls, such as face masks, social

distancing and disinfection in the household setting, may inform community


epidemic control and prevent transmission of COVID-19 in households.

Methods

Study population and design

We conducted a retrospective cohort study involving families of laboratory

confirmed COVID-19 cases in Beijing, China. We defined family members as

those who had lived with primary cases in a house for 4 days before and for

more than 24 hours after the primary cases developed illness related to

COVID-19. As of 21 February 2020, all laboratory confirmed COVID-19

cases reported in Beijing were enrolled in our study and followed-up. The

outcome of interest was secondary transmission in the household. Families

with secondary transmission were defined as those where some or all of the

family members become infected within one incubation period (2 weeks) of

symptom onset of the primary case.

To analyse the predictors of household transmission, we compared families

with and without secondary transmission for various measured risk factors,

preventive interventions and exposures.

Definition of confirmed case

According to national prevention and control guideline (fifth edition),7

confirmed cases were those who met the clinical, epidemiological and

laboratory testing criteria for COVID-19 simultaneously.

Clinical criteria included: (a) fever and/or one or more respiratory

symptoms; (b) radiological evidence of pneumonia; (c) white blood cell

count normal or decreased, and lymphocyte count decreased at the early

stage of illness.

Epidemiological criteria included: (a) visits to/living in Wuhan or cities

around Wuhan or other communities which had already reported COVID-19


cases in the 14 days prior to the onset of symptoms; (b) having contact with

a person known to have infection with SARS-CoV-2 in the 14 days prior to

onset of symptoms; (c) having contact with a person who had fever or

respiratory symptoms and came from Wuhan or adjacent cities or other

communities which had already reported COVID-19 cases in the 14 days

prior to onset of symptoms; (d) being one of the cluster cases.

Suspected cases met one of the epidemiological criteria and ·any two of the

clinical criteria, or met all of the clinical criteria. Confirmed cases were those

suspected cases who met one of the following criteria.: (a) respiratory or

blood specimen tested positive for SARS-CoV-2 by real time reverse

transcriptase-polymerase chain reaction; (b) virus in respiratory or blood

specimen was highly homologous with known SARS-CoV-2 through gene

sequencing.

Data collection

A three part structured questionnaire was developed. The first part included

demographic and clinical information of the primary case. The second part

was mainly focused on the primary case's knowledge about and attitudes

toward COVID-19, and their self-reported practices (mask wearing, social

distancing, living arrangements) and activities in the home. The third part

was about self-reported behaviours of all family members, as well as the

family's accommodation and household hygiene practices from 4 days

before the illness onset to the day the primary case was isolated, including

room ventilation, room cleaning and disinfection. Close contact was defined

as being within 1 m or 3 feet of the primary case, such as eating around a

table or sitting together watching TV. The frequency of contact, disinfection

and ventilation was measured.

After diagnosis, the primary case was hospitalised as per standard practice

in Beijing. Eligible primary cases and their family members were interviewed

between 28 February and 8 March. Data on the primary case were


extracted from epidemiological investigating reports from Beijing Centre for Disease Prevention and Control and supplemented by interview.

The clinical severity of the COVID-19 case was categorised as mild, severe or critical. Mild disease included non-pneumonia and mild pneumonia cases. Severe disease was characterised by dyspnoea, respiratory

frequency ~30/min, blood oxygen saturation s93%, PaO2/FiO2 ratio <300 and/or lung infiltrates >50% within 24-48 hours. Critical cases were those who exhibited respiratory failure, septic shock and/or multiple organ dysfunction/failure.a

Statistical analysis

Risk factors for secondary transmission were analysed by characteristics of the primary case, characteristics of well family members and household hygiene practices. Categorical variables are presented as counts and percentages, and continuous variables as medians (IQR). The x2 test and Fisher exact test were applied to compare difference between groups when necessary. A composite COVID-19 knowledge score and hand hygiene score were created with multiple sub-questions. A multivariable logistic regression model was used to identify risk factors associated with SARSCoV-2 household transmission. Univariable analysis was first performed with all measures and only those variables significant at p<0.1 could be selected in the following multivariable logistic regression analysis. Backward elimination was performed to establish a final model retaining those with p<0.05 in the model. Statistical analyses were performed using SAS software (V.9.4).

Ethics statement

As our study was embedded within the COVID-19 prevention and control practice within public health units, and the telephone interview was a supplementary survey of the epidemiological field investigation, ethics


approval was not required. We obtained subjects' verbal informed consent before the start of the interviews.

Patient and public involvement

No patients or the public were involved in the study design, setting the research questions, interpretation or writing up of results, or reporting of the research.

Results

As of 21 February 2020, 399 confirmed COVID-19 cases in 181 families were reported in Beijing. Four family clusters were excluded because we were unable to determine whether there was secondary transmission or coexposure, leaving 177 families. After reviewing information in the epidemiological investigation reports and survey calls, 40 families were excluded as they did not meet the study inclusion criteria. A further 13 families declined to be interviewed and were also excluded, leaving 124 families for study (figure 1).

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Figure 1

Selection and inclusion of interviewing subjects. Summary of household enrolment, and inclusion and interview response in the analysis of SARS-CoV-2 household transmission in Beijing, China.

Over the 2 weeks of follow-up from onset of the primary case, secondary

transmission occurred in 41/124 families (77 secondary cases), and 83/124

families had no secondary transmission. The overall secondary attack rate

in families was 23.0% (77/335). In the secondary transmission group, 41

primary cases caused 77 secondary cases, with a median secondary case

number in families of 2 (IQR 1-2). In the secondary transmission group, the

secondary attack rate in children <18 years of age was 36.1% (13/36),

compared with 69.6% (64/92) in adults, and the difference between these

two age groups was significant (x2=12.08, p<0.001). The median age of the 13 secondary child cases was 3 years (IQR 2-6), 12/13 were mild and 1/13

was asymptomatic. Of 64 secondary adult cases, 82.8% (53/64) were mild,

10.9% (7/64) were severe, 1.6% (1/64) was critical and 4.7% (3/64) were

asymptomatic. No statistically significant difference was observed in clinical severity between 41 index adult cases (table 1) and 64 secondary adult

cases for the secondary transmission group (p=0.18).

Table 1

Characteristics of primary cases of COVID-19: univariable analysis

Table 2

Characteristics of well family members: univariable analysis

Table3

Characteristics of the residence and household practices: univariable analysis between two family groups

The univariable analysis for association with secondary transmission of

SARS-CoV-2 within families is shown in tables 1-3. Significant associations APPENDIX TO JAMES CASCIANO DECLARATION-79

were:

Characteristics, behaviours and knowledge of the primary case: having

diarrhoea, interval from illness onset to medical isolation >2 days, self

awareness of being infected with SARS-CoV-2 when the primary case

developed the illness, lack of knowledge of their own infectiousness, mask

wearing in the home after illness onset, failing to self-isolate and not eating

separately were associated with transmission (table 1).

Behaviours of family members: having daily close contact with the primary

case at home, and number of family members wearing a mask in the home

before and after the primary case's illness onset date were associated with

transmission (table 2).

Household practices: frequency of using chlorine or ethanol based

disinfectant for household cleaning and household ventilation duration were

protective (table 3).

In multivariable logistic regression model, four factors remained significantly

associated with secondary transmission. The primary case having diarrhoea

in the home and daily close contact with the primary case in the home

increased the risk. Transmission was significantly reduced by frequent use

of chlorine or ethanol based disinfectant in households and family members

(including the primary case) wearing a mask at home before the primary

case developed the illness (table 4).

Table4

Risk factors for SARS-CoV-2 household transmission: multivariable analysis

Discussion

This study confirms that the highest risk of household transmission is prior

to symptom onset, but that precautionary NPls, such as mask use, APPENDIX TO JAMES CASCIANO DECLARATION-SO

disinfection and social distancing in households can prevent COVID-19 transmission during the pandemic. This study is the first to confirm the effectiveness of mask use prior to symptom onset by family members, daily household disinfection and social distancing in the home. This could inform precautionary guidelines for families to reduce intrafamilial transmission in areas where there is high community transmission or other risk factors for COVID-19. Household transmission is a major driver of epidemic growth.5 6 Further, in countries where health system capacity is exhausted, many people with infection are required to self-isolate at home, where their household contacts will be at risk of infection. In our study, the median family size of the 124 families was 4 (range 2-9), usually with children, parents and grandparents, which is similar to the social structure of most Chinese families.9 Therefore, the risk of SARS-CoV-2 household transmission is high if a primary case was introduced and no measure was adopted. We showed that NPls are effective at preventing transmission, even in homes that are crowded and small. UFMU is a low risk intervention with potential public health benefits.3 4 The results suggest that community face mask use is likely to be the most effective inside the household during severe epidemics.

Almost a quarter of family members became infected, and the findings suggest that the risk was highest either before symptom onset or early in the clinical illness, as most primary cases were hospitalised after diagnosis, and interventions were not effective if applied after symptom onset. In the univariate analysis, wearing a mask after illness onset was significant, but in multivariate analysis, only wearing it before symptom onset was effective. Viral load is highest in the 2 days before symptom onset and on the first day of symptoms, and up to 44% of transmission is during the pre-symptomatic period in settings with substantial household clustering.10 11 This supports UFMU, probably by reducing onward transmission from people in the presymptomatic phase of the illness1213 as well as protecting well mask users. Randomised clinical trials of face masks in the household have confirmed protection against other respiratory viruses if compliant, if used


within 36 hours of the primary case symptom onset, and alone or in

combination with hand hygiene.1415 This study now provides specific

evidence for UFMU in settings of high epidemic growth to protect against

COVID-19. In our study, 91.2% (103/113) of primary cases had a high score

on hand hygiene, but it was not effective, confirming the results of previous

randomised clinical trials which showed hand hygiene alone did not protect

against respiratory transmissible viruses, but masks combined with hand

hygiene did have effect.16

As the compliance of UFMU would be poor in the home, there was difficulty

and also no necessity for everyone to wear masks at home. We

recommended that those families with members who were at risk of getting

infected with SARS-CoV-2 (such as ever having contact with a COVID-19

patient, medical workers caring for a COVID-19 patient or having a history

of travelling to high risk areas) should apply UFMU to reduce the risk of

household transmission.

This study showed that social distancing within the home is effective and

having close contact (within 1 m or 3 feet, such as eating around a table or

sitting together watching TV) is a risk factor for transmission. The study

also provides evidence of effectiveness of chlorine or ethanol based

household disinfection in areas with high community transmission, or where

one family member is a health worker, or where there is a risk of COVID-19,

such as during home quarantine, consistent with advice provided by local

health authorities or organisations.17 Diarrhoea as a symptom in the

primary case is also a risk factor for SARS-CoV-2 transmission within

families, which highlights the importance of disinfection of the bathroom

and toilet, as well as closing the toilet lid when flushing to prevent

aerosolisation of the virus.

Our study has limitations. Telephone interview has inherent limitations,

including recall bias. It would take about 20 min to complete an interview,

and 95% (118/124) of interviews were rated as informative by the


interviewers. The evaluation results of mask wearing were reliable, but we

did not collect data on the concentration of disinfectant used by families.

The strengths of the study were that we had complete follow-up data and

were able to accurately ascertain the incidence of secondary transmission

in the cohort.

Conclusions

Household transmission in the pre-symptomatic or early symptomatic

period of COVID-19 is a driver of epidemic growth and any measure aimed

at reducing this can flatten the curve. This study reinforces the high risk of

transmission in households but importantly shows that UFMU and hygiene

measures can significantly reduce the risk of household transmission of

COVID-19, independent of household size or crowding. This is the first

study to show the effectiveness of precautionary mask use, social

distancing and regular disinfection in the household, and can inform

guidelines for prevention of household transmission. The results may also

be informative for families of high risk groups, such as health workers,

quarantined individuals or situations where cases of COVID-19 have to be

managed at home.

Acknowledgments

We thank the staff members in the district and municipal Centres for

Disease Prevention and Control, and medical settings in Beijing for

conducting field investigation, specimen collection, laboratory detection

and case reporting. We also thank all patients and families involved in the

study.

References

1. +J

2. +J


3. +J

4. +J

5. +J

6. +J

7. +J

8. +J

9. +J

10. +J

11. +J

12. +J

13. +J

14. +J

15. +J

16. +J

17. +J


Case-Control Study of Use of Personal Protective Measures and Risk for SARS-CoV 2 Infection, Thailand We evaluated effectiveness of personal protective measures against severe

acute respiratory disease coronavirus 2 (SARS-CoV-2) infection. Our case

control study included 211 cases of coronavirus disease (COVID-19) and

839 controls in Thailand. Cases were defined as asymptomatic contacts of

COVID-19 patients who later tested positive for SARS-CoV-2; controls were

asymptomatic contacts who never tested positive. Wearing masks all the

time during contact was independently associated with lower risk for SARS

CoV-2 infection compared with not wearing masks; wearing a mask

sometimes during contact did not lower infection risk. We found the type of

mask worn was not independently associated with infection and that

contacts who always wore masks were more likely to practice social

distancing. Maintaining >1 m distance from a person with COVID-19, having

close contact for <15 minutes, and frequent handwashing were

independently associated with lower risk for infection. Our findings support

consistent wearing of masks, handwashing, and social distancing to protect

against COVID-19.

Evaluation of the effectiveness of mask-wearing to protect healthy persons

in the general public from infection with severe acute respiratory syndrome

coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease

(COVID-19), is urgently needed (7,2). On February 27, 2020, during the

early stages of the COVID-19 outbreak, the World Health Organization

(WHO) announced that wearing a mask of any type was not recommended

for asymptomatic persons (3). The rationale at that time was to avoid

unnecessary cost, procurement burden, and a false sense of security (3).


Several systematic reviews found no conclusive evidence to support

widespread use of masks in public settings to protect against respiratory

infectious diseases, such as influenza and severe acute respiratory

syndrome (SARS) (4-6). However, China, South Korea, Japan, Thailand, and

other countries in Asia have recommended the use of face masks among

the general public since early in the COVID-19 pandemic (7). Evidence

suggests that persons with COVID-19 can have a presymptomatic period,

during which they can be contagious and transmit SARS-CoV-2 to others

before symptoms develop (8). These findings led to a change in

recommendations from the US Centers for Disease Control and Prevention

on April 4, 2020, that advised all persons wear a cloth face covering when in

public (9). On April 6 and June 5, 2020, WHO updated its advice on the use

of masks for the general public and encouraged countries that issue the

recommendations to conduct research on this topic (8).

Thailand has been implementing multiple measures against transmission of

SARS-CoV-2 since the beginning of the outbreak (10, 11). The country

established thermal screening at airports on January 3, 2020, and detected

an early case of COVID-19 outside China in a traveler from Wuhan, China,

arriving at Bangkok Suvarnabhumi airport on January 8, 2020 (10). Thailand

uses Surveillance and Rapid Response Teams (SRRTs), together with village

health volunteers, to conduct contact tracing, educate the public about

COVID-19, and monitor close contacts of persons with COVID-19 in

quarantine (11). SRRTs are epidemiologic teams trained to conduct

surveillance, investigations, and initial control of communicable diseases,

such as SARS and influenza (12, 13). More than 1,000 district-, provincial-,

and regional-level SRRTs are working on COVID-19 contact tracing in

Thailand.

By February 2020, public pressure to wear masks in Thailand was high.

However, medical masks became difficult for the public to procure, and the

government categorized medical masks as price-controlled goods. When

the Ministry of Public Health (MoPH) designated COVID-19 a dangerous


communicable disease, according to the Communicable Disease Act of

2015, government officials were empowered to quarantine case-contacts

and close venues (14, 15). On March 3, MoPH recommended public use of

cloth face masks (16). On March 18, schools, universities, bars, nightclubs,

and entertainment venues were closed (17). On March 26, when the country

was reporting »100-150 new COVID-19 cases per day, the government

declared a national state of emergency, prohibited public gatherings, and

enforced wearing of face masks by all persons on public transport (18). On

April 21, MoPH announced 19 new PCR-confirmed COVID-19 cases,

bringing the total number of cases to 2,811 (78). Given the lack of evidence,

we sought to evaluate the effectiveness of mask-wearing, handwashing,

social distancing, and other personal protective measures against SARS

CoV-2 infection in public in Thailand.

Study Design

We conducted a retrospective case-control study by drawing persons with

COVID-19 cases and noninfected controls from a cohort of contact tracing

records of the central SRRT team at the Department of Disease Control

(DDC), MoPH, Thailand. We included contact investigations of 3 large

COVID-19 clusters in nightclubs, boxing stadiums, and a state enterprise

office in Thailand.

Contacts were defined by DDC as persons who had activities with or were

in the same location as a person with confirmed COVID-19 (19,20). The

main aim of contact tracing was to identify and evaluate contacts, perform

reverse transcription PCR (RT-PCR) diagnostic tests, and quarantine high

risk contacts, as defined by the MoPH (AP-.cendix). RT-PCR was performed

at laboratories certified for COVID-19 testing by the National Institute of

Health of Thailand (79,20). Data on risk factors associated with SARS-CoV-

2 infection, such as type of contact and use of mask, were recorded during

contact investigations, but data sometimes were incomplete.

The central SRRT performed contact investigations for clusters of >5 PCRAPPENDIX TO JAMES CASCIANO DECLARATION-87

confirmed COVID-19 cases from the same location within a 1-week period

(79,20). We used these data to identify contacts who were asymptomatic

during March 1-31, 2020. We used all available contact tracing records of

the central SRRT in the study.

We telephoned contacts during April 30-May 27, 2020, and asked details

about their contact with a COVID-19 index patient, such as dates, locations,

duration, and distance of contact. We asked whether contacts wore a mask

during the contact with the index patient, the type of mask, and the

frequency of wearing a mask, which we defined as compliance with mask

wearing. We asked whether and how frequently contacts washed their

hands while with the index patient. We asked whether contacts performed

social distancing and whether they had physical contact with the COVID-19

index patient. If they did not know, or could not remember, contact with the

index patient, we asked whether they had contact with other persons at the

location. We asked whether the contact shared a cup or a cigarette with

other persons in the place they had contact or had highest risk for contact

with the index patient and whether the COVID-19 index patient, if known to

the respondent, had worn a mask {AP-Qendix, Additional Methods). We also

asked, and verified by using DDC records, whether and when the contacts

had symptoms and when COVID-19 was diagnosed.

For our study, we defined cases as asymptomatic contacts who later tested

positive for SARS-CoV-2, on the basis of RT-PCR results available by April

21, 2020. We defined controls as asymptomatic contacts who did not have

positive test results for SARS-CoV-2 by April 21, including those who tested

negative and those who were not tested. We defined asymptomatic

contacts as persons who had contact with or were in the same location as a

symptomatic COVID-19 patient and had no symptoms of COVID-19 on the

first day of contact. We defined index patients as persons identified from

contact tracing data as the potential source of SARS-CoV-2 infection; cases

{as defined above) also could be index patients. We defined primary index

patients as persons whose probable sources of infection were before the


study period, March 1-31; for whom we were not able to identify the source

of infection; or whose probable sources of infection were outside the

contact tracing data included in the study. We defined high-risk exposure

as that which occurred when persons lived in the same household as a

COVID-19 patient; had a direct physical contact with a COVID-19 patient;

were <1 m from a COVID-19 patient for >15 minutes; or were in the same

closed environment, such as a room, nightclub, stadium, or vehicle, <1 m

from a COVID-19 patient for >15 minutes.

We used 21 days after March 31 as a cutoff date based on evidence that

most persons with COVID-19 likely would develop symptoms within 14 days

(27) and that it could take <7 additional days for symptomatic persons

under contact investigation to go to a healthcare facility and be tested for

COVID-19. Our study follows the STROBE guidelines (22).

Statistical Analysis

To include only initially asymptomatic contacts in the study, we excluded

persons who reported having symptoms of COVID-19 at the time of initial

contact with an index patient. Because our study focused on the risk for

infection in the community, we excluded contacts whose contact locations

were healthcare facilities. We also excluded primary index patients if they

were the first to have symptoms at the contact investigation location, had

symptoms since the first day of visiting the location, or were the origin of

infection based on the contact investigation.

We estimated secondary attack rates by using the percentage of new cases

among asymptomatic contacts with high-risk exposure to enable

comparison with other studies. We estimated odds ratios (ORs) and 95%

Cls for associations between developing COVID-19 and factors evaluated.

We used logistic regression with random effects for location and for index

patients nested in the same location. If an asymptomatic contact had

contact with >1 symptomatic COVID-19 index patient, the interviewer

identified the index patient as the symptomatic COVID-19 patient with the APPENDIX TO JAMES CASCIANO DECLARATION-89

closest contact. The percentage of missing values for the variable

indicating whether the index patients wore a mask was 27%; thus, we did

not include this variable in our analyses. For other variables, we assumed

that missing values were missing at random and used imputation by

chained equations (23,24). We created 10 imputed datasets and the

imputation model included the case-control indicator and variables used in

the multivariable models, including sex, age group, contact place, shortest

distance of contact, duration of contact at <1 m, sharing dishes or cups,

sharing cigarettes, handwashing, mask-wearing, and compliance with

mask-wearing. We developed the final multilevel mixed-effect logistic

regression models on the basis of previous knowledge and a purposeful

selection method (25; ApQendix, Additional Analyses). Because of

collinearity between mask use and mask type, we conducted a separate

analysis including mask type in the multilevel mixed-effects logistic

regression model for SARS-CoV-2 infection. We also tested a predefined

interaction between mask type and compliance with mask-wearing

(ApQendix, Additional Analyses).

To clarify patterns of behavior and factors related to compliance with mask

wearing, we used multinomial logistic regression models and the imputed

dataset to estimated OR and 95% Cl for associations between 3 mask

wearing compliance categories, never, sometimes, or all the time; and for

other practices, including handwashing and social distancing during the

contact period. We used logistic regression to estimate p values for

pairwise comparisons.

To estimate the proportional reduction in cases that would occur if

exposure to risk factors was reduced, we estimated the population

attributable fraction by using the imputed dataset and a direct method

based on logistic regression, as described previously (26,27; AQQendix,

Additional Analyses). We performed all analyses by using Stata version 14.2

{StataCorp, httgs:fLwww.stata.com) and R version 4.0.0 {R Foundation for

Statistical Computing, httgs:fLwww.r-groject.org).


Characteristics of the Cohort Data

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The contact tracing records of the central

SRRT included 1,716 persons who had contact

with or were in the same location as a person

with diagnosed COVID-19 in an investigation

of 3 large clusters (Figure 1). Overall, 18 Figure 1. Flow diagram in case

primary index patients were identified: 11 from control study of severe acute

the nightclub cluster, 5 from the boxing respiratory syndrome coronavirus 2 infections and contacts, Thailand,

stadiums cluster, and 2 from the state March-April 2020. covI0-19,

enterprise office cluster. Timelines of primary coronavirus disease; SARS-cov-2,

index patients from the 3 clusters varied

(AP-Qendix Figures 1-3); we excluded the 18

primary index patients from our analyses.

Characteristics of Cases and Controls

severe acute respiratory syndrome coronavirus 2; SRRT, Surveillance ...

After interviewing each contact by phone and applying the exclusion criteria

(Figure 1), our analysis included 1,050 asymptomatic persons who had

contact with or were in the same location as a symptomatic COVID-19 index

patient during March 1-31, 2020. The median age of persons included was

38 years (IQR 28-51 years); 55% were male, and 45% were female (Table 1).

Most (61%; n = 645) asymptomatic contacts included in the study were

associated with the boxing stadiums cluster, 36% (n = 374) were related to

the nightclub cluster, and 3% (n = 31) were related to the state enterprise

office cluster. Overall, 890 (84.8%) contacts were considered to have high

risk exposure.

Among 1,050 asymptomatic contacts included in our analysis, 211 (20.1%)

tested positive for SARS-CoV-2 by April 21, 2020, and were classified as

cases; 839 (79.9%) never tested positive and were controls. Of the 211

cases, 195 (92.4%) had high-risk exposures and 150 (71.1%) had symptoms

before COVID-19 diagnosis by RT-PCR (AQP-endix). The last date that a

COVID-19 case was detected was April 9, 2020. Among the 839 controls, APPENDIX TO JAMES CASCIANO DECLARATION-91

695 (82.8%) had high-risk exposures and 719 (85.7%) were tested by PCR

at least once.

Among asymptomatic contacts included in the A.:_..:

study, 228 had contact with a COVID-19 index .. ; . :-: · .

patient at nightclubs, 144 at boxing stadiums, · i~'( and 20 at the state enterprise office (Figure 2).

The others had contacts with a COVID-19

index patient at workplaces (n = 277),

households (n = 230), and other places (n =

. ,. ...

8

151). Among 890 asymptomatic contacts with c :-~.-.

high-risk exposures included in the study, the ._., Figure 2. Development and secondary attack rate from boxing stadiums transmission of severe acute

was 86% (111/129), the secondary attack rate respiratory syndrome coronavirus 2

for nightclubs was 18.2% (34/187), the among asymptomatic contacts, Thailand, March-April 2020. Clusters

household secondary attack rate was 16.5% indicate coronavirus disease (COVID(38/230), the workplace secondary attack rate19) contacts from nightclubs (A);

was 4.9% (10/205), and the secondary attack boxing stadiums (B), and the ...

rate at other places was 1.4% (2/139).

Bivariate Analyses

Our analysis showed risk for SARS-CoV-2 infection was negatively

associated with personal protective measures {Table 1). Crude odds ratio

{OR) for infection was 0.08 {95% Cl 0.02-0.31) for those maintaining a

distance of >1 m from a COVID-19 patient; 0.13 (95% Cl 0.04-0.46) for

those whose duration of contact was s15 minutes; 0.41 (95% Cl 0.18-0.91)

for those who performed handwashing sometimes; 0.19 (95% Cl 0.08-0.46)

for those who washed hands often; and 0.16 (95% Cl 0.07-0.36) for those

wearing a mask all the time during contact with a COVID-19 patient. We

noted a higher risk for SARS-CoV-2 infection among persons sharing dishes

or cups {OR 2.71; 95% Cl 1.48-4.94) and sharing cigarettes {OR 6.12; 95%

Cl 2.12-17.72) with other persons in general, not necessarily including a


COVID-19 patient. In the bivariate model, type of mask was associated with

risk for infection (p = 0.003).

Multivariable Analyses

We found a negative association between risk for SARS-CoV-2 infection

and maintaining a distance of >1 m from a COVID-19 patient (adjusted odds

ratio [aOR] 0.15; 95% Cl 0.04-0.63); duration of contact <15 minutes (aOR

0.24; 95% Cl 0.07-0.90); handwashing often (aOR 0.33; 95% Cl 0.13-0.87);

and wearing a mask all the time during contact with a COVID-19 patient

(aOR 0.23; 95% Cl 0.09-0.60) (Table 1). Wearing masks sometimes during

contact with a COVID-19 patient was not statistically significantly

associated with lower risk for infection (aOR 0.87; 95% Cl 0.41-1.84).

Sharing cigarettes with other persons was associated with higher risk for

infection (aOR 3.47; 95% Cl 1.09-11.02).

Compliance with mask-wearing during contact with a COVID-19 patient was

strongly associated with lower risk for infection in the multivariable model.

Because of collinearity with mask-wearing compliance, we did not include

mask type in the final model. We included mask type in a separate

multivariable model and found type of mask was not independently

associated with infection (p = 0.54) (AQgendix Table 1). We found no

evidence of effect modification between mask type and mask-wearing

compliance.

Association Between Mask-Wearing Compliance and Other Social Distancing Practices

Because mask-wearing throughout the contact period was negatively

associated with COVID-19, we further explored characteristics of

participants to ascertain whether wearing a mask produced a potential false

sense of security. We found that during the contact period, 25% of persons

who wore masks all the time reported maintaining >1 m distance from

contacts compared with 18% of persons who did not wear a mask (pairwise


p = 0.03). In addition, persons who wore masks all the time were more likely

to report duration of contact <15 minutes (26% vs. 13% for those who did

not wear a mask; pairwise p<0.001) and washing hands often (79% vs. 26%

for those who did not wear a mask; pairwise p<0.001) (Table 2). We found

that 43% of persons who wore masks sometimes were likely to wash their

hands often compared with those who did not wear masks (26%; pairwise

p<0.001), but they were more likely to have physical contact (50% vs. 42%;

pairwise p = 0.03) and report duration of contact >60 minutes (75% vs.

67%; pairwise p = 0.04) compared with those who did not wear masks.

Our findings provide evidence that mask-wearing, handwashing, and social

distancing are independently associated with lower risk for SARS-CoV-2

infection in the general public in community settings in Thailand. We

observed that wearing masks throughout the period of exposure to

someone infected with SARS-CoV-2 was associated with lower risk for

infection, but wearing masks only sometimes during the period was not.

This evidence supports recommendations to wear masks consistently and

correctly at all times in public (2,7-9).

The effectiveness of mask-wearing we observed is consistent with previous

studies, including a randomized-controlled trial showing that consistent

face mask use reduced risk for influenza-like illness (28), 2 case-control

studies that found that mask-wearing was associated with lower risk for

SARS infection (29,30), and a retrospective cohort study that found that

mask-wearing by index patients or family members at home was associated

with lower risk for SARS-CoV-2 infection (31). Previous studies found use of

surgical masks or similar 12-16-layer cotton reusable masks demonstrated

protection against coronavirus infection in the community (32), but we did

not observe a difference between wearing nonmedical and medical masks

in the general population. Our results suggest that wearing nonmedical

masks in public can potentially reduce transmission of SARS-CoV-2.

Another study found perception of risk of developing COVID-19 can

increase a person's likelihood of wearing a medical mask in nonmedical


settings (T.D. Huynh, unpub. data,

httQs :/ Lwww. med rxiv.orgL contentL10 .1101L20 2 0.0 3. 2 6. 2 0 044388v1).

However, given supply shortages, medical masks should be reserved for

use by healthcare workers.

We found a negative association between risk for SARS-CoV-2 infection

and social distancing, consistent with previous studies that found that >1 m

physical distancing was associated with a large protective effect and

distances of >2 m could be more effective (32). Our findings on

effectiveness of hand hygiene also were consistent with reports in previous

studies (33).

In this study, secondary attack rates at different venues varied widely. The

household secondary attack rate in our study {16.5%) is comparable with

ranges reported previously (11o/o-23%) (34,35), and relatively high

compared with workplaces (4.9%) and other settings {1.4%). Although

quarantine measures can be challenging and sometimes impractical,

household members should immediately separate a person who develops

symptoms of COVID-19; the sick person should stay in a specific room; use

a separate bathroom, if possible; and not share dishes, cups, and other

utensils (36). All household members should wear masks, frequently wash

their hands, and perform social distancing to the extent possible (37).

The high number of COVID-19 cases associated with nightclub exposures

in Bangkok is comparable to a COVID-19 outbreak associated with the

ltaewon nightclub cluster in Seoul, South Korea, during May 2020 (38), in

which persons visited several nightclubs in the same area during a short

period of time. The secondary attack rate in boxing stadiums was high

(86%) but similar to a cluster of COVID-19 cases associated with a football

match in Italy during February 2020 (39). The secondary attack rate of

COVID-19 at a choir practice in the United States was reported to be

53.3o/o-86.7% (40). Secondary attack rates in public gathering places with

high densities of persons shouting anet cheering, such as football and


boxing stadiums, are still uncertain but appear to be high.

Clear and consistent public messaging from policy makers likely can

prevent a false sense of security and promote compliance with social

distancing in Thailand. We found that those who wore masks throughout

the time they were exposed to a COVID-19 patient also were more likely to

wash their hands and perform social distancing. Traditional and social

media outlets can support public health responses by working with

governments to provide consistent, simple, and clear messages (47). In

Thailand, daily briefings from the Centre for COVID-19 Situation

Administration provided clear, consistent messages on social distancing,

how to put on a mask, and how to wash hands, which might have improved

public confidence with the recommendations. Consistent public messages

on how to wear masks correctly also are needed, particularly for those who

wear masks sometimes or incorrectly, such as not covering both nose and

mouth. We found that persons who only intermittently wore masks during

exposure also did not practice social distancing adequately.

Our study has several limitations. First, because our findings were based on

contacts related to 3 major COVID-19 clusters in Thailand during March

2020, they might not be generalizable to all settings. Second, estimated

ORs were conditioned on reported contact with index patients; our study

did not evaluate or consider the probability of having contact with other

infected persons in the community, which could have occurred. Third,

because only 89% of controls were tested, those not tested could have

been infected; therefore, cases might have been missed in persons with

mild or no symptoms or who did not report symptoms or seek care or

testing. Nonetheless, we believe that misclassification likely was minimal

because those who were not tested with RT-PCR were low-risk contacts;

the small number likely would not change our main findings and

recommendations on personal protective measures. Fourth, identifying

every potential contact can be nearly impossible because some persons

might have had contact with >1 COVID-19 patient. Hence, our estimated


secondary attack rates among contacts with high-risk exposure could be

overestimated or underestimated. Fifth, population attributable fraction is

based on several assumptions, including causality, and should be

interpreted with caution (42,43). Finally, findings were subject to common

biases of retrospective case-control studies, including memory bias,

observer bias, and information bias (44). To reduce potential biases, we

used structured interviews in which each participant was asked the same

set of defined questions.

As many countries begin to relax social distancing measures, our findings

provide evidence supporting consistent mask-wearing, handwashing, and

adhering to social distancing recommendations to reduce SARS-CoV-2

transmission in public gatherings. Wearing nonmedical masks in public

could help slow the spread of COVID-19. Complying with all measures could

be highly effective; however, in places with a high population density,

additional measures might be required.

Clear and consistent public messaging on personal protective

recommendations is essential, particularly for targeting those who wear

masks intermittently or incorrectly. Our data showed that no single

protective measure was associated with complete protection from COVID-

19. All measures, including mask-wearing, handwashing, and social

distancing, can increase protection against COVID-19 in public settings.

Dr. Pawinee Doung-ngern is the head of Communicable Disease Unit,

Bureau of Epidemiology, Department of Disease Control, Ministry of Public

Health, Thailand. Her primary research interests include the public health

and epidemiology of communicable diseases.

Top


Physical interventions to interrupt or reduce the spread of respiratory

• viruses BACKGROUND: Viral epidemics or pandemics of acute respiratory

infections (ARls) pose a global threat. Examples are influenza (H1N1)

caused by the H1N1pdm09 virus in 2009, severe acute respiratory

syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID-19)

caused by SARS-CoV-2 in 2019. Antiviral drugs and vaccines may be

insufficient to prevent their spread. This is an update of a Cochrane Review

published in 2007, 2009, 2010, and 2011. The evidence summarised in this

review does not include results from studies from the current COVID-19

pandemic.

OBJECTIVES: To assess the effectiveness of physical interventions to

interrupt or reduce the spread of acute respiratory viruses.

SEARCH METHODS: We searched CENTRAL, PubMed, Embase, CINAHL

on 1 April 2020. We searched ClinicalTrials.gov, and the WHO ICTRP on 16

March 2020. We conducted a backwards and forwards citation analysis on

the newly included studies.

SELECTION CRITERIA: We included randomised controlled trials (RCTs)

and cluster-RCTs of trials investigating physical interventions (screening at

entry ports, isolation, quarantine, physical distancing, personal protection,

hand hygiene, face masks, and gargling) to prevent respiratory virus

transmission. In previous versions of this review we also included

observational studies. However, for this update, there were sufficient RCTs

to address our study aims.

DATA COLLECTION AND ANALYSIS: We used standard methodological

procedures expected by Cochrane. We used GRADE to assess the certainty


of the evidence. Three pairs of review authors independently extracted data

using a standard template applied in previous versions of this review, but

which was revised to reflect our focus on RCTs and cluster-RCTs for this

update. We did not contact trialists for missing data due to the urgency in

completing the review. We extracted data on adverse events (harms)

associated with the interventions.

MAIN RESULTS: We included 44 new RCTs and cluster-RCTs in this

update, bringing the total number of randomised trials to 67. There were no

included studies conducted during the COVID-19 pandemic. Six ongoing

studies were identified, of which three evaluating masks are being

conducted concurrent with the COVID pandemic, and one is completed.

Many studies were conducted during non-epidemic influenza periods, but

several studies were conducted during the global H1 N1 influenza pandemic

in 2009, and others in epidemic influenza seasons up to 2016. Thus, studies

were conducted in the context of lower respiratory viral circulation and

transmission compared to COVID-19. The included studies were conducted

in heterogeneous settings, ranging from suburban schools to hospital

wards in high-income countries; crowded inner city settings in low-income

countries; and an immigrant neighbourhood in a high-income country.

Compliance with interventions was low in many studies. The risk of bias for

the RCTs and cluster-RCTs was mostly high or unclear. Medical/surgical

masks compared to no masks We included nine trials (of which eight were

cluster-RCTs) comparing medical/surgical masks versus no masks to

prevent the spread of viral respiratory illness (two trials with healthcare

workers and seven in the community). There is low certainty evidence from

nine trials (3507 participants) that wearing a mask may make little or no

difference to the outcome of influenza-like illness (ILi) compared to not

wearing a mask (risk ratio (RR) 0.99, 95% confidence interval (Cl) 0.82 to

1.18. There is moderate certainty evidence that wearing a mask probably

makes little or no difference to the outcome of laboratory-confirmed

influenza compared to not wearing a mask (RR 0.91, 95% Cl 0.66 to 1.26; 6

trials; 3005 participants). Harms were rarely measured and poorly reported. APPENDIX TO JAMES CASCIANO DECLARATION-99

Two studies during COVID-19 plan to recruit a total of 72,000 people. One

evaluates medical/surgical masks (N = 6000) (published Annals of Internal

Medicine, 18 Nov 2020), and one evaluates cloth masks (N = 66,000).

N95/P2 respirators compared to medical/surgical masks We pooled trials

comparing N95/P2 respirators with medical/surgical masks (four in

healthcare settings and one in a household setting). There is uncertainty

over the effects of N95/P2 respirators when compared with

medical/surgical masks on the outcomes of clinical respiratory illness (RR

0.70, 95% Cl 0.45 to 1.10; very low-certainty evidence; 3 trials; 7779

participants) and ILi (RR 0.82, 95% Cl 0.66 to 1.03; low-certainty evidence;

5 trials; 8407 participants). The evidence is limited by imprecision and

heterogeneity for these subjective outcomes. The use of a N95/P2

respirator compared to a medical/surgical mask probably makes little or no

difference for the objective and more precise outcome of laboratory

confirmed influenza infection (RR 1.10, 95% Cl 0.90 to 1.34; moderate

certainty evidence; 5 trials; 8407 participants). Restricting the pooling to

healthcare workers made no difference to the overall findings. Harms were

poorly measured and reported, but discomfort wearing medical/surgical

masks or N95/P2 respirators was mentioned in several studies. One

ongoing study recruiting 576 people compares N95/P2 respirators with

medical surgical masks for healthcare workers during COVID-19. Hand

hygiene compared to control Settings included schools, childcare centres,

homes, and offices. In a comparison of hand hygiene interventions with

control (no intervention), there was a 16% relative reduction in the number

of people with ARls in the hand hygiene group (RR 0.84, 95% Cl 0.82 to

0.86; 7 trials; 44,129 participants; moderate-certainty evidence),

suggesting a probable benefit. When considering the more strictly defined

outcomes of ILi and laboratory-confirmed influenza, the estimates of effect

for ILi (RR 0.98, 95% Cl 0.85 to 1.13; 10 trials; 32,641 participants; low

certainty evidence) and laboratory-confirmed influenza (RR 0.91, 95% Cl

0.63 to 1.30; 8 trials; 8332 participants; low-certainty evidence) suggest

the intervention made little or no difference. We pooled all 16 trials (61,372


participants) for the composite outcome of ARI or ILi or influenza, with each

study only contributing once and the most comprehensive outcome

reported. The pooled data showed that hand hygiene may offer a benefit

with an 11% relative reduction of respiratory illness (RR 0.89, 95% Cl 0.84 to

0.95; low-certainty evidence), but with high heterogeneity. Few trials

measured and reported harms. There are two ongoing studies of

handwashing interventions in 395 children outside of COVID-19. We

identified one RCT on quarantine/physical distancing. Company employees

in Japan were asked to stay at home if household members had ILi

symptoms. Overall fewer people in the intervention group contracted

influenza compared with workers in the control group (2.75% versus 3.18%;

hazard ratio 0.80, 95% Cl 0.66 to 0.97). However, those who stayed at

home with their infected family members were 2.17 times more likely to be

infected. We found no RCTs on eye protection, gowns and gloves, or

screening at entry ports.

AUTHORS' CONCLUSIONS: The high risk of bias in the trials, variation in

outcome measurement, and relatively low compliance with the interventions

during the studies hamper drawing firm conclusions and generalising the

findings to the current COVID-19 pandemic. There is uncertainty about the

effects of face masks. The low-moderate certainty of the evidence means

our confidence in the effect estimate is limited, and that the true effect may

be different from the observed estimate of the effect. The pooled results of

randomised trials did not show a clear reduction in respiratory viral infection

with the use of medical/surgical masks during seasonal influenza. There

were no clear differences between the use of medical/surgical masks

compared with N95/P2 respirators in healthcare workers when used in

routine care to reduce respiratory viral infection. Hand hygiene is likely to

modestly reduce the burden of respiratory illness. Harms associated with

physical interventions were under-investigated. There is a need for large,

well-designed RCTs addressing the effectiveness of many of these

interventions in multiple settings and populations, especially in those most

at risk of ARls. APPENDIX TO JAMES CASCIANO DECLARATION-101

Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings-Personal Protective and Environmental Measures Personal Protective Measures

Hand Hygiene

We identified a recent systematic review by ~:.=: ~;-;-;~~~-,---~ Wong et al. on RCTs designed to assess the ::=~~ttt i ~~~ =~ti .. ~-~-..

efficacy of hand hygiene interventions against §:r:: j§7§~~if;~7--transmission of laboratory-confirmed :::.~::~:~-: .~:: ::: : ·:.

-----influenza (8). We used this review as a starting;::.;_~_~~~~~~~~=· . -: point and then searched for additional :::~t-{~ ~ ~ J I~-i ~-: -··-···-j-. -·---··--•. literature published after 2013; we found 3 -----

. . . . . . . Figure 1. Meta-analysis of risk ratios add1t1onal ehg1ble articles pubhshed dunng the for the effect of hand hygiene with or search period of January 1, 2013-August 13, without face mask use on laboratory-2018. In total we identified 12 articles (9-20) confirm~d influenza fro~ 10 .

' ' randomized controlled trials with of which 3 articles were from the updated >11,000 participants. A) Hand search and 9 articles from Wong et al. (8). Twohygiene alone; ...

articles relied on the same underlying dataset (16, 19); therefore, we counted these 2 articles as 1 study, which resulted in 11 RCTs. We further selected 10 studies with >10,000 participants for inclusion in the metaanalysis (Figure 1). We excluded 1 study from the meta-analysis because it provided estimates of infection risks only at the household level, not the individual level (20). We did not generate an overall pooled effect of hand hygiene only or of hand hygiene with or without face mask because of high heterogeneity in individual estimates (12 87 and 82%, respectively). The effect of hand hygiene combined with face masks on laboratory-confirmed


influenza was not statistically significant {RR 0.91, 95% Cl 0.73-1.13; 12 = 35%, p = 0.39). Some studies reported being underpowered because of limited sample size, and low adherence to hand hygiene interventions was observed in some studies.

We further analyzed the effect of hand hygiene by setting because transmission routes might vary in different settings. We found 6 studies in

household settings examining the effect of hand hygiene with or without face masks, but the overall pooled effect was not statistically significant (RR 1.05, 95% Cl 0.86-1.27; /2 = 57%, p = 0.65) (AP-gendix Figure 4) (11-15, 17).

The findings of 2 studies in school settings were different {Aggendix Figure 5). A study conducted in the United States (76) showed no major effect of hand hygiene, whereas a study in Egypt (18) reported that hand hygiene reduced the risk for influenza by >50%. A pooled analysis of 2 studies in university residential halls reported a marginally significant protective effect of a combination of hand hygiene plus face masks worn by all residents {RR 0.48, 95% Cl 0.21-1.08; /2 = 0%, p = 0.08) (AP-gendix Figure 6) (9, 10).

In support of hand hygiene as an effective measure, experimental studies have reported that influenza virus could survive on human hands for a short time and could transmit between hands and contaminated surfaces (2,21).

Some field studies reported that influenza A(H1N1)pdm09 and influenza A{H3N2) virus RNA and viable influenza virus could be detected on the hands of persons with laboratory-confirmed influenza (22,23), supporting the potential of direct and indirect contact transmission to play a role in the spread of influenza. Other experimental studies also demonstrated that hand hygiene could reduce or remove infectious influenza virus from human hands (24,25). However, results from our meta-analysis on RCTs did not provide evidence to support a protective effect of hand hygiene against transmission of laboratory-confirmed influenza. One study did report a major effect, but in this trial of hand hygiene in schools in Egypt, running water had to be installed and soap and hand-drying material had to be introduced into the intervention schools as part of the project (18).


Therefore, the impact of hand hygiene might also be a reflection of the

introduction of soap and running water into primary schools in a lower

income setting. If one considers all of the evidence from RCTs together, it is

useful to note that some studies might have underestimated the true effect

of hand hygiene because of the complexity of implementing these

intervention studies. For instance, the control group would not typically

have zero knowledge or use of hand hygiene, and the intervention group

might not adhere to optimal hand hygiene practices (11, 13, 15).

Hand hygiene is also effective in preventing other infectious diseases,

including diarrheal diseases and some respiratory diseases (8,26). The

need for hand hygiene in disease prevention is well recognized among most

communities. Hand hygiene has been accepted as a personal protective

measure in >50% of national preparedness plans for pandemic influenza

(5). Hand hygiene practice is commonly performed with soap and water,

alcohol-based hand rub, or other waterless hand disinfectants, all of which

are easily accessible, available, affordable, and well accepted in most

communities. However, resource limitations in some areas are a concern

when clean running water or alcohol-based hand rub are not available.

There are few adverse effects of hand hygiene except for skin irritation

caused by some hand hygiene products (27). However, because of certain

social or religious practices, alcohol-based hand sanitizers might not be

permitted in some locations (28). Compliance with proper hand hygiene

practice tends to be low because habitual behaviors are difficult to change

(29). Therefore, hand hygiene promotion programs are needed to advocate

and encourage proper and effective hand hygiene.

Respiratory Etiquette

Respiratory etiquette is defined as covering the nose and mouth with a

tissue or a mask (but not a hand) when coughing or sneezing, followed by

proper disposal of used tissues, and proper hand hygiene after contact with

respiratory secretions (30). Other descriptions of this measure have


included turning the head and covering the mouth when coughing and

coughing or sneezing into a sleeve or elbow, rather than a hand. The

rationale for not coughing into hands is to prevent subsequent

contamination of other surfaces or objects (31). We conducted a search on

November 6, 2018, and identified literature that was available in the

databases during 1946-November 5, 2018. We did not identify any

published research on the effectiveness of respiratory etiquette in reducing

the risk for laboratory-confirmed influenza or ILi. One observational study

reported a similar incidence rate of self-reported respiratory illness (defined

by >1 symptoms: cough, congestion, sore throat, sneezing, or breathing

problems) among US pilgrims with or without practicing respiratory

etiquette during the Hajj (32). The authors did not specify the type of

respiratory etiquette used by participants in the study. A laboratory-based

study reported that common respiratory etiquette, including covering the

mouth by hands, tissue, or sleeve/arm, was fairly ineffective in blocking the

release and dispersion of droplets into the surrounding environment on the

basis of measurement of emitted droplets with a laser diffraction system

(31).

Respiratory etiquette is often listed as a preventive measure for respiratory

infections. However, there is a lack of scientific evidence to support this

measure. Whether respiratory etiquette is an effective nonpharmaceutical

intervention in preventing influenza virus transmission remains

questionable, and worthy of further research.

Face Masks

In our systematic review, we identified 10 RCTs that reported estimates of

the effectiveness of face masks in reducing laboratory-confirmed influenza

virus infections in the community from literature published during 1946-July

27, 2018. In pooled analysis, we found no significant reduction in influenza

transmission with the use of face masks (RR 0.78, 95% Cl 0.51-1.20;

/2 = 30%, p = 0.25) (Figure 2). One study evaluated the use of masks among


pilgrims from Australia during the Hajj A - --- -- --- _ .. _ ----••-. . . . .. ·••-- ~-pilgrimage and reported no major difference in =)f·; ~ : ~j ?~ •·

·--- - .. -- .. - . the risk for laboratory-confirmed influenza a·=-;~ · _______ ::_ ___ ~~

virus infection in the control or mask group

(33). Two studies in university settings

-...... - ......... -····.. . - . - ·- ·-.. . . =:: -~ .· . : = : : :-: ; :: -:: ·~ -·· ... - . . . . - ·-.. . . --- ,.. ---·-·-- . -·-- ··-. c_ .- -------- --

assessed the effectiveness of face masks for ~-:f{: i ~ i ~ ~~ tii { =:L~--= -. : ~ ~ ; ::: :_: ::.: ~'

primary protection by monitoring the incidence:_-_-:_...;:-:~ ·--~ ·· ·· · ;;;.~ · _;_-

of laboratory-confirmed influenza among Figure 2. Meta-analysis of risk ratios • for the effect of face mask use with

student hall residents for 5 months (9, 10). The or without enhanced hand hygiene on

overall reduction in ILi or laboratory-confirmed laboratory-confirmed influenza from

influenza cases in the face mask group was 10 randomized controlled trials with >6,500 participants. A) Face mask ...

not significant in either studies (9, 10). Study

designs in the 7 household studies were slightly different: 1 study provided

face masks and P2 respirators for household contacts only (34), another

study evaluated face mask use as a source control for infected persons only

(35), and the remaining studies provided masks for the infected persons as

well as their close contacts (11-13, 15, 17). None of the household studies

reported a significant reduction in secondary laboratory-confirmed

influenza virus infections in the face mask group (11-13, 15, 17,34,35). Most

studies were underpowered because of limited sample size, and some

studies also reported suboptimal adherence in the face mask group.

Disposable medical masks (also known as surgical masks) are loose-fitting

devices that were designed to be worn by medical personnel to protect

accidental contamination of patient wounds, and to protect the wearer

against splashes or sprays of bodily fluids (36). There is limited evidence

for their effectiveness in preventing influenza virus transmission either when

worn by the infected person for source control or when worn by uninfected

persons to reduce exposure. Our systematic review found no significant

effect of face masks on transmission of laboratory-confirmed influenza.

We did not consider the use of respirators in the community. Respirators are

tight-fitting masks that can protect the wearer from fine particles (37) and


should provide better protection against influenza virus exposures when

properly worn because of higher filtration efficiency. However, respirators,

such as N95 and P2 masks, work best when they are fit-tested, and these

masks will be in limited supply during the next pandemic. These specialist

devices should be reserved for use in healthcare settings or in special

subpopulations such as immunocompromised persons in the community,

first responders, and those performing other critical community functions,

as supplies permit.

In lower-income settings, it is more likely that reusable cloth masks will be

used rather than disposable medical masks because of cost and availability

(38). There are still few uncertainties in the practice of face mask use, such

as who should wear the mask and how long it should be used for. In theory,

transmission should be reduced the most if both infected members and

other contacts wear masks, but compliance in uninfected close contacts

could be a problem (12,34). Proper use of face masks is essential because

improper use might increase the risk for transmission (39). Thus, education

on the proper use and disposal of used face masks, including hand hygiene,

is also needed.

Surface and Object Cleaning

For the search period from 1946 through October 14, 2018, we identified 2

RCTs and 1 observational study about surface and object cleaning

measures for inclusion in our systematic review (4D-42). One RCT

conducted in day care nurseries found that biweekly cleaning and

disinfection of toys and linen reduced the detection of multiple viruses,

including adenovirus, rhinovirus, and respiratory syncytial virus in the

environment, but this intervention was not significant in reducing detection

of influenza virus, and it had no major protective effect on acute respiratory

illness (41). Another RCT found that hand hygiene with hand sanitizer

together with surface disinfection reduced absenteeism related to

gastrointestinal illness in elementary schools, but there was no major


reduction in absenteeism related to respiratory illness (42). A cross

sectional study found that passive contact with bleach was associated with

a major increase in self-reported influenza (40).

Given that influenza virus can survive on some surfaces for prolonged

periods (43), and that cleaning or disinfection procedures can effectively

reduce or inactivate influenza virus from surfaces and objects in

experimental studies (44), there is a theoretical basis to believe that

environmental cleaning could reduce influenza transmission. As an

illustration of this proposal, a modeling study estimated that cleaning of

extensively touched surfaces could reduce influenza A infection by 2% (45).

However, most studies of influenza virus in the environment are based on

detection of virus RNA by PCR, and few studies reported detection of viable

virus.

Although we found no evidence that surface and object cleaning could

reduce influenza transmission, this measure does have an established

impact on prevention of other infectious diseases (42). It should be feasible

to implement this measure in most settings, subject to the availability of

water and cleaning products. Although irritation caused by cleaning

products is limited, safety remains a concern because some cleaning

products can be toxic or cause allergies (40).


A cluster randomised trial of cloth masks compared with medical masks in healthcare workers Strengths and limitations of this study

• The use of cloth masks is widespread around the world, particularly in

countries at high-risk for emerging infections, but there have been no

efficacy studies to underpin their use.

• This study is large, a prospective randomised clinical trial (RCT) and

the first RCT ever conducted of cloth masks.

• The use of cloth masks are not addressed in most guidelines for health

care workers-this study provides data to update guidelines.

• The control arm was 'standard practice: which comprised mask use in

a high proportion of participants. As such (without a no-mask control),

the finding of a much higher rate of infection in the cloth mask arm

could be interpreted as harm caused by cloth masks, efficacy of

medical masks, or most likely a combination of both.

Introduction

The use of facemasks and respirators for the protection of healthcare

workers (HCWs) has received renewed interest following the 2009 influenza

pandemic, 1 and emerging infectious diseases such as avian influenza,2

Middle East respiratory syndrome coronavirus (MERS-coronavirus)3 ,4 and

Ebola virus.5 Historically, various types of cloth/cotton masks (referred to

here after as 'cloth masks') have been used to protect HCWs.6 Disposable

medical/surgical masks (referred to here after as 'medical masks') were

introduced into healthcare in the mid 19th century, followed later by


respirators.7 Compared with other parts of the world, the use of face masks

is more prevalent in Asian countries, such as China and Vietnam.8-11

In high resource settings, disposable medical masks and respirators have

long since replaced the use of cloth masks in hospitals. Yet cloth masks

remain widely used globally, including in Asian countries, which have

historically been affected by emerging infectious diseases, as well as in

West Africa, in the context of shortages of personal protective equipment

(PPE).12 ,13 It has been shown that medical research disproportionately

favours diseases of wealthy countries, and there is a lack of research on the

health needs of poorer countries.14 Further, there is a lack of high-quality

studies around the use of facemasks and respirators in the healthcare

setting, with only four randomised clinical trials (RCTs) to date.15 Despite

widespread use, cloth masks are rarely mentioned in policy documents,16

and have never been tested for efficacy in a RCT. Very few studies have

been conducted around the clinical effectiveness of cloth masks, and most

available studies are observational or in vitro.6 Emerging infectious diseases

are not constrained within geographical borders, so it is important for global

disease control that use of cloth masks be underpinned by evidence. The

aim of this study was to determine the efficacy of cloth masks compared

with medical masks in HCWs working in high-risk hospital wards, against

the prevention of respiratory infections.

Methods

A cluster-randomised trial of medical and cloth mask use for HCWs was

conducted in 14 hospitals in Hanoi, Vietnam. The trial started on the 3

March 2011, with rolling recruitment undertaken between 3 March 2011 and

10 March 2011. Participants were followed during the same calendar time

for 4 weeks of facemasks use and then one additional week for appearance

of symptoms. An invitation letter was sent to 32 hospitals in Hanoi, of which

16 agreed to participate. One hospital did not meet the eligibility criteria;

therefore, 74 wards in 15 hospitals were randomised. Following the


randomisation process, one hospital withdrew from the study because of a

nosocomial outbreak of rubella.

Participants provided written informed consent prior to initiation of the trial.

Randomisation

Seventy-four wards (emergency, infectious/respiratory disease, intensive

care and paediatrics) were selected as high-risk settings for occupational

exposure to respiratory infections. Cluster randomisation was used because

the outcome of interest was respiratory infectious diseases, where

prevention of one infection in an individual can prevent a chain of

subsequent transmission in closed settings.a ,9 Epi info V.6 was used to

generate a randomisation allocation and 74 wards were randomly allocated

to the interventions.

From the eligible wards 1868 HCWs were approached to participate. After

providing informed consent, 1607 participants were randomised by ward to

three arms: (1) medical masks at all times on their work shift; (2) cloth

masks at all times on shift or (3) control arm (standard practice, which may

or may not include mask use). Standard practice was used as control

because the IRB deemed it unethical to ask participants to not wear a mask.

We studied continuous mask use (defined as wearing masks all the time

during a work shift, except while in the toilet or during tea or lunch breaks)

because this reflects current practice in high-risk settings in Asia.a

The laboratory results were blinded and laboratory testing was conducted

in a blinded fashion. As facemask use is a visible intervention, clinical end

points could not be blinded. Figure 1 outlines the recruitment and

randomisation process.


Assessed for eligibility

( I S hospitals)

Didaotmeet J, clip,itity criteria.

Randomised to IP I hmpilal

1607HCWs

I 9

l l Mediml Mask tlothmasks Conqpl

Received allocated Received allocated Followed up

intervention intervention 4S8(HCWs)

SIO(HCWs) S69(HCWs)

1 1 I Analysed An@lysed Analvsed

S80HCWs S69HCWs 4S8HCWs

Figure 1

Consort diagram of recruitment and follow-up (HCWs, healthcare workers).

Primary end points

There were three primary end points for this study, used in our previous

mask RCTs:8 ,9 (1) Clinical respiratory illness (CRI), defined as two or more

respiratory symptoms or one respiratory symptom and a systemic

symptom;17 (2) influenza-like illness (ILi), defined as fever ~38°C plus one

respiratory symptom and (3) laboratory-confirmed viral respiratory

infection. Laboratory confirmation was by nucleic acid detection using

multiplex reverse transcriptase PCR (RT-PCR) for 17 respiratory viruses:

respiratory syncytial virus (RSV) A and B, human metapneumovirus (hMPV),

influenza A (H3N2), (H1N1)pdm09, influenza B, parainfluenza viruses 1-4,

influenza C, rhinoviruses, severe acute respiratory syndrome (SARS)

associated coronavirus (SARS-CoV), coronaviruses 229E, NL63, OC43 and

HKU1, adenoviruses and human bocavirus (hBoV).18-23 Additional end

points included compliance with mask use, defined as using the mask

during the shift for 70% or more of work shift hours.9 HCWs were


categorised as 'compliant' if the average use was equal or more than 70%

of the working time. HCW were categorised as 'non-compliant' if the

average mask use was less than 70% of the working time.

Eligibility

Nurses or doctors aged ~,a years working full-time were eligible. Exclusion

criteria were: (1) Unable or refused to consent; (2) Beards, long moustaches

or long facial hair stubble; (3) Current respiratory illness, rhinitis and/or

allergy.

Intervention

Participants wore the mask on every shift for four consecutive weeks.

Participants in the medical mask arm were supplied with two masks daily for

each 8 h shift, while participants in the cloth mask arm were provided with

five masks in total for the study duration, which they were asked to wash

and rotate over the study period. They were asked to wash cloth masks with

soap and water every day after finishing the shifts. Participants were

supplied with written instructions on how to clean their cloth masks. Masks

used in the study were locally manufactured medical (three layer, made of

non-woven material) or cloth masks (two layer, made of cotton) commonly

used in Vietnamese hospitals. The control group was asked to continue with

their normal practices, which may or may not have included mask wearing.

Mask wearing was measured and documented for all participants, including

the control arm.

Data collection and follow-up

Data on sociodemographic, clinical and other potential confounding factors

were collected at baseline. Participants were followed up daily for 4 weeks

(active intervention period), and for an extra week of standard practice, in

order to document incident infection after incubation. Participants received


a thermometer (traditional glass and mercury) to measure their temperature

daily and at symptom onset. Daily diary cards were provided to record

number of hours worked and mask use, estimated number of patient

contacts (with/without ILi) and number/type of aerosol-generating

procedures (AGPs) conducted, such as suctioning of airways, sputum

induction, endotracheal intubation and bronchoscopy. Participants in the

cloth mask and control group (if they used cloth masks) were also asked to

document the process used to clean their mask after use.

We also monitored compliance with mask use by a previously validated self

reporting mechanism.a Participants were contacted daily to identify

incident cases of respiratory infection. If participants were symptomatic,

swabs of both tonsils and the posterior pharyngeal wall were collected on

the day of reporting.

Sample collection and laboratory testing

Trained collectors used double rayon-tipped, plastic-shafted swabs to

scratch tonsillar areas as well as the posterior pharyngeal wall of

symptomatic participants. Testing was conducted using RT-PCR applying

published methods.19-23 Viral RNA was extracted from each respiratory

specimen using the Viral RNA Mini kit (Qiagen, Germany), following the

manufacturer's instructions. The RNA extraction step was controlled by

amplification of a RNA house-keeping gene (amplify pGEM) using real-time

RT-PCR. Only extracted samples with the house keeping gene detected by

real-time RT-PCR were submitted for multiplex RT-PCR for viruses.

The reverse transcription and PCRs were performed in OneStep (Qiagen,

Germany) to amplify viral target genes, and then in five multiplex RT-PCR:

RSVA/B, influenza A/H3N2, A(H1N1) and B viruses, hMPV (reaction mix 1);

parainfluenza viruses 1-4 (reaction mix 2); rhinoviruses, influenza C virus,

SARS-CoV (reaction mix 3); coronaviruses OC43, 229E, NL63 and HKU1

(reaction mix 4); and adenoviruses and hBoV (reaction mix 5), using a


method published by others.18 All samples with viruses detected by

multiplex RT-PCR were confirmed by virus-specific mono nested or

heminested PCR. Positive controls were prepared by in vitro transcription to

control amplification efficacy and monitor for false negatives, and included

in all runs (except for NL63 and HKU1). Each run always included two

negatives to monitor amplification quality. Specimen processing, RNA

extraction, PCR amplification and PCR product analyses were conducted in

different rooms to avoid cross-contamination.19 ,20

Filtration testing

The filtration performance of the cloth and medical masks was tested

according to the respiratory standard AS/NZS1716.24 The equipment used

was a TSI 8110 Filter tester. To test the filtration performance, the filter is

challenged by a known concentration of sodium chloride particles of a

specified size range and at a defined flow rate. The particle concentration is

measured before and after adding the filter material and the relative

filtration efficiency is calculated. We examined the performance of cloth

masks compared with the performance levels-P1, P2 (=N95) and P3, as

used for assessment of all particulate filters for respiratory protection. The

3M 9320 N95 and 3M Vflex 9105 N95 were used to compare against the

cloth and medical masks.

Sample size calculation

To obtain 80% power at two-sided 5% significance level for detecting a

significant difference of attack rate between medical masks and cloth

masks, and for a rate of infection of 13% for cloth mask wearers compared

with 6% in medical mask wearers, we would need eight clusters per arm

and 530 participants in each arm, and intracluster correlation coefficient

(ICC) 0.027, obtained from our previous study.a The design effect (deft) for

this cluster randomisation trial was 1.65 (deff=1+(m-1)xlCC=1+

(25-1)x0.027=1.65). As such, we aimed to recruit a sample size of 1600


participants from up to 15 hospitals.

Analysis

Descriptive statistics were compared among intervention and control arms.

Primary end points were analysed by intention to treat. We compared the

event rates for the primary outcomes across study arms and calculated p

values from cluster-adjusted x2 tests25 and ICC.25 ,26 We also estimated

relative risk (RR) after adjusting for clustering using a log-binomial model

under generalised estimating equation (GEE) framework.27 We checked for

variables which were unequally distributed across arms, and conducted an

adjusted analysis accordingly. We fitted a multivariable log-binomial model,

using GEE to account for clustering by ward, to estimate RR after adjusting

for potential confounders. In the initial model, we included all the variables

that had p value less than 0.25 in the univariable analysis, along with the

main exposure variable (randomisation arm). A backward elimination

method was used to remove the variables that did not have any

confounding effect.

As most participants in the control arm used a mask during the trial period,

we carried out a post-hoc analysis comparing all participants who used only

a medical mask (from the control arm and the medical mask arm) with all

participants who used only a cloth mask (from the control arm and the cloth

arm). For this analysis, controls who used both types of mask (n=245) or

used N95 respirators (n=3) or did not use any masks (n=2) were excluded.

We fitted a multivariable log-binomial model, to estimate RR after adjusting

for potential confounders. As we pooled data of participants from all three

arms and analysed by mask type, not trial arm, we did not adjust for

clustering here. All statistical analyses were conducted using STATA V.12.28

Owing to a very high level of mask use in the control arm, we were unable to

determine whether the differences between the medical and cloth mask

arms were due to a protective effect of medical masks or a detrimental


effect of cloth masks. To assist in interpreting the data, we compared rates

of infection in the medical mask arm with rates observed in medical mask

arms from two previous RCTs,8 ,9 in which no efficacy of medical masks

could be demonstrated when compared with control or N95 respirators,

recognising that seasonal and geographic variation in virus activity affects

the rates of exposure {and hence rates of infection outcomes) among

HCWs. This analysis was possible because the trial designs were similar

and the same outcomes were measured in all three trials. The analysis was

carried out to determine if the observed results were explained by a

detrimental effect of cloth masks or a protective effect of medical masks.

Results

A total of 1607 HCWs were recruited into the study. The participation rate

was 86% (1607/1868). The average number of participants per ward was 23

and the mean age was 36 years. On average, HCWs were in contact with 36

patients per day during the trial period {range 0-661 patients per day,

median 20 patients per day). The distribution of demographic variables was

generally similar between arms {table 1). Figure 2 shows the primary

outcomes for each of the trial arms. The rates of CRI, ILi and la~oratory

confirmed virus infections were lowest in the medical mask arm, followed by

the control arm, and highest in the cloth mask arm.

Table 1

Demographic and other characteristics by arm of randomisation


7.6

- S.4

3.3

2.3

CRI Virus IU

■ Ooth masks ■ Control ■ Medical mask

Figure 2

0.2

Outcomes in trial arms (CRI, clinical respiratory illness; Ill, influenza-like illness; Virus, laboratory-confirmed viruses).

Table 2 shows the intention-to-treat analysis. The rate of CRI was highest in

the cloth mask arm, followed by the control arm, and lowest in the medical

mask arm. The same trend was seen for ILi and laboratory tests confirmed

viral infections. In intention-to-treat analysis, ILi was significantly higher

among HCWs in the cloth masks group (RR=13.25 and 95% Cl 1.74 to

100.97), compared with the medical masks group. The rate of ILi was also

significantly higher in the cloth masks arm (RR=3.49 and 95% Cl 1.00 to

12.17), compared with the control arm. Other outcomes were not

statistically significant between the three arms.

Table 2

Intention-to-treat analysis

Among the 68 laboratory-confirmed cases, 58 (85%) were due to

rhinoviruses. Other viruses detected were hMPV (7 cases), influenza B (1

case), hMPV/rhinovirus co-infection (1 case) and influenza B/rhinovirus co

infection (1 case) (table 3). No influenza A or RSV infections were detected.

Table 3

Type of virus isolated APPENDIX TO JAMES CASCIANO DECLARATION-119

Compliance was significantly higher in the cloth mask arm (RR=2.41, 95% Cl

2.01 to 2.88) and medical masks arm (RR=2.40, 95% Cl 2.00 to 2.87),

compared with the control arm. Figure 3 shows the percentage of

participants who were compliant in the three arms. A post-hoc analysis

adjusted for compliance and other potential confounders showed that the

rate of ILi was significantly higher in the cloth mask arm (RR=13.00, 95% Cl

1.69 to 100.07), compared with the medical masks arm (table 4). There was

no significant difference between the medical mask and control arms. Hand

washing was significantly protective against laboratory-confirmed viral

infection (RR=0.66, 95% Cl 0.44 to 0.97).

Table 4

Multivariable cluster-adjusted log-binomial model to calculate RR for

study outcomes

70 56.6" 56.8%

(52.5-60.5%) (52.7-60.8")

so

" 111D 40 a 23.6% C

~ 30 (19.9-27.7") -

~

20

10

--,

Medical mask Ooth mask Control

Figure 3

Compliance with the mask wearing-mask wearing more than 70% of working hours.

In the control arm, 170/458 (37%) used medical masks, 38/458 (8%) used

cloth masks, and 245/458 (53%) used a combination of both medical and

cloth masks during the study period. The remaining 1% either reported

using a N95 respirator (n=3) or did not use any masks (n=2).


Table 5 shows an additional analysis comparing all participants who used

only a medical mask (from the control arm and the medical mask arm) with

all participants who used only a cloth mask (from the control arm and the

cloth arm). In the univariate analysis, all outcomes were significantly higher

in the cloth mask group, compared with the medical masks group. After

adjusting for other factors, ILi (RR=6.64, 95% Cl 1.45 to 28.65) and

laboratory-confirmed virus (RR=1.72, 95% Cl 1.01 to 2.94) remained

significantly higher in the cloth masks group compared with the medical masks group.

Table 5

Univariate and adjusted analysis comparing participants who used medical masks and cloth masks*

Table 6 compares the outcomes in the medical mask arm with two

previously published trials.a ,9 This shows that while the rates of CRI were

significantly higher in one of the previously published trials, the rates of

laboratory-confirmed viruses were not significantly different between the

three trials for medical mask use.

Table 6

A comparison of outcome data for the medical mask arm with medical mask outcomes in previously published RCTs

On average, HCWs worked for 25 days during the trial period and washed

their cloth masks for 23/25 (92%) days. The most common approach to

washing cloth masks was self-washing (456/569, 80%), followed by

combined self-washing and hospital laundry (91/569, 16%), and only

hospital laundry (22/569, 4%). Adverse events associated with facemask

use were reported in 40.4% (227/562) of HCWs in the medical mask arm

and 42.6% (242/568) in the cloth mask arm (p value 0.450). General

discomfort (35.1%, 397/1130) and breathing problems (18.3%, 207/1130)


were the most frequently reported adverse events.

Laboratory tests showed the penetration of particles through the cloth

masks to be very high (97%) compared with medical masks (44%) (used in

trial) and 3M 9320 N95 (<0.01%), 3M Vflex 9105 N95 (0.1%).

Discussion

We have provided the first clinical efficacy data of cloth masks, which

suggest HCWs should not use cloth masks as protection against respiratory

infection. Cloth masks resulted in significantly higher rates of infection than

medical masks, and also performed worse than the control arm. The

controls were HCWs who observed standard practice, which involved mask

use in the majority, albeit with lower compliance than in the intervention

arms. The control HCWs also used medical masks more often than cloth

masks. When we analysed all mask-wearers including controls, the higher

risk of cloth masks was seen for laboratory-confirmed respiratory viral

infection.

The trend for all outcomes showed the lowest rates of infection in the

medical mask group and the highest rates in the cloth mask arm. The study

design does not allow us to determine whether medical masks had efficacy

or whether cloth masks were detrimental to HCWs by causing an increase in

infection risk. Either possibility, or a combination of both effects, could

explain our results. It is also unknown whether the rates of infection

observed in the cloth mask arm are the same or higher than in HCWs who

do not wear a mask, as almost all participants in the control arm used a

mask. The physical properties of a cloth mask, reuse, the frequency and

effectiveness of cleaning, and increased moisture retention, may potentially

increase the infection risk for HCWs. The virus may survive on the surface

of the facemasks,29 and modelling studies have quantified the

contamination levels of masks.30 Self-contamination through repeated use

and improper doffing is possible. For example, a contaminated cloth mask


may transfer pathogen from the mask to the bare hands of the wearer. We

also showed that filtration was extremely poor (almost 0%) for the cloth

masks. Observations during SARS suggested double-masking and other

practices increased the risk of infection because of moisture, liquid

diffusion and pathogen retention.31 These effects may be associated with cloth masks.

We have previously shown that N95 respirators provide superior efficacy to

medical masks,8 ,9 but need to be worn continuously in high-risk settings

to protect HCWs.9 Although efficacy for medical masks was not shown,

efficacy of a magnitude that was too small to be detected is possible.a ,9

The magnitude of difference between cloth masks and medical masks in the

current study, if explained by efficacy of medical masks alone, translates to

an efficacy of 92% against ILi, which is possible, but not consistent with the

lack of efficacy in the two previous RCTs.8 ,9 Further, we found no

significant difference in rates of virus isolation in medical mask users

between the three trials, suggesting that the results of this study could be

interpreted as partly being explained by a detrimental effect of cloth masks.

This is further supported by the fact that the rate of virus isolation in the

no-mask control group in the first Chinese RCT was 3.1%, which was not

significantly different to the rates of virus isolation in the medical mask arms

in any of the three trials including this one. Unlike the previous RCTs,

circulating influenza and RSV were almost completely absent during this

study, with rhinoviruses comprising 85% of isolated pathogens, which

means the measured efficacy is against a different range of circulating

respiratory pathogens. Influenza and RSV predominantly transmit through

droplet and contact routes, while Rhinovirus transmits through multiple

routes, including airborne and droplet routes.32 ,33 The data also show

that the clinical case definition of ILi is non-specific, and captures a range

of pathogens other than influenza. The study suggests medical masks may

be protective, but the magnitude of difference raises the possibility that

cloth masks cause an increase in infection risk in HCWs. Further, the

filtration of the medical mask used in this trial was poor, making extremely APPENDIX TO JAMES CASCIANO DECLARATION-123

high efficacy of medical masks unlikely, particularly given the predominant

pathogen was rhinovirus, which spreads by the airborne route. Given the

obligations to HCW occupational health and safety, it is important to

consider the potential risk of using cloth masks.

In many parts of the world, cloth masks and medical masks may be the only

options available for HCWs. Cloth masks have been used in West Africa

during the Ebola outbreak in 2014, due to shortages of PPE, (personal

communication, M Jalloh). The use of cloth masks is recommended by

some health organisations, with caveats.34-36 In light of our study, and the

obligation to ensure occupational health and safety of HCWs, cloth masks

should not be recommended for HCWs, particularly during AGPs and in

high-risk settings such as emergency, infectious/respiratory disease and

intensive care wards. Infection control guidelines need to acknowledge the

widespread real-world practice of cloth masks and should comprehensively

address their use. In addition, other important infection control measure

such as hand hygiene should not be compromised. We confirmed the

protective effects of hand hygiene against laboratory-confirmed viral

infection in this study, but mask type was an independent predictor of

clinical illness, even adjusted for hand hygiene.

A limitation of this study is that we did not measure compliance with hand

hygiene, and the results reflect self-reported compliance, which may be

subject to recall or other types of bias. Another limitation of this study is the

lack of a no-mask control group and the high use of masks in the controls,

which makes interpretation of the results more difficult. In addition, the

quality of paper and cloth masks varies widely around the world, so the

results may not be generalisable to all settings. The lack of influenza and

RSV (or asymptomatic infections) during the study is also a limitation,

although the predominance of rhinovirus is informative about pathogens

transmitted by the droplet and airborne routes in this setting. As in previous

studies, exposure to infection outside the workplace could not be

estimated, but we would assume it to be equally distributed between trial


arms. The major strength of the randomised trial study design is in ensuring

equal distribution of confounders and effect modifiers (such as exposure outside the workplace) between trial arms.

Cloth masks are used in resource-poor settings because of the reduced

cost of a reusable option. Various types of cloth masks (made of cotton,

gauze and other fibres) have been tested in vitro in the past and show lower

filtration capacity compared with disposable masks.7 The protection

afforded by gauze masks increases with the fineness of the cloth and the

number of layers,37 indicating potential to develop a more effective cloth

mask, for example, with finer weave, more layers and a better fit.

Cloth masks are generally retained long term and reused multiple times,

with a variety of cleaning methods and widely different intervals of

cleaning.34 Further studies are required to determine if variations in

frequency and type of cleaning affect the efficacy of cloth masks.

Pandemics and emerging infections are more likely to arise in low-income or

middle-income settings than in wealthy countries. In the interests of global

public health, adequate attention should be paid to cloth mask use in such

settings. The data from this study provide some reassurance about medical

masks, and are the first data to show potential clinical efficacy of medical

masks. Medical masks are used to provide protection against droplet

spread, splash and spray of blood and body fluids. Medical masks or

respirators are recommended by different organisations to prevent

transmission of Ebola virus, yet shortages of PPE may result in HCWs being

forced to use cloth masks.38-40 In the interest of providing safe, low-cost

options in low income countries, there is scope for research into more

effectively designed cloth masks, but until such research is carried out,

cloth masks should not be recommended. We also recommend that

infection control guidelines be updated about cloth mask use to protect the

occupational health and safety of HCWs.


Acknowledgments

The authors would like to thank the staff members from the National

Institute of Hygiene and Epidemiology, Hanoi, Vietnam, who were involved

with the trial. They thank as well to the staff from the Hanoi hospitals who

participated. They also acknowledge the support of 3M for testing of

filtration of the facemasks. 3M was industry partner in the ARC linkage

project grant; however they were not involved in study design, data

collection or analysis. The 3M products were not used in this study.

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Household Transmission of SARSCoV-2 Key Points

Question What is the household secondary attack rate for severe acute

respiratory syndrome coronavirus 2 (SARS-CoV-2)?

Findings In this meta-analysis of 54 studies with 77 758 participants, the

estimated overall household secondary attack rate was 16.6%, higher than

observed secondary attack rates for SARS-CoV and Middle East respiratory

syndrome coronavirus. Controlling for differences across studies,

secondary attack rates were higher in households from symptomatic index

cases than asymptomatic index cases, to adult contacts than to child

contacts, to spouses than to other family contacts, and in households with 1

contact than households with 3 or more contacts.

Meaning These findings suggest that households are and will continue to

be important venues for transmission, even in areas where community

transmission is reduced.

Abstract

Importance Crowded indoor environments, such as households, are high

risk settings for the transmission of severe acute respiratory syndrome

coronavirus 2 (SARS-CoV-2).

Objectives To examine evidence for household transmission of SARS-CoV-

2, disaggregated by several covariates, and to compare it with other

coronaviruses.

Data Source PubMed, searched through October 19, 2020. Search terms

included SARS-CoV-2 or COVJD-19 with secondary attack rate, household,


close contacts, contact transmission, contact attack rate, or family transmission.

Study Selection All articles with original data for estimating household

secondary attack rate were included. Case reports focusing on individual

households and studies of close contacts that did not report secondary

attack rates for household members were excluded.

Data Extraction and Synthesis Meta-analyses were done using a

restricted maximum-likelihood estimator model to yield a point estimate and

95% Cl for secondary attack rate for each subgroup analyzed, with a

random effect for each study. To make comparisons across exposure types,

study was treated as a random effect, and exposure type was a fixed

moderator. The Preferred Reporting Items for Systematic Reviews and

Meta-analyses (PRISMA) reporting guideline was followed.

Main Outcomes and Measures Secondary attack rate for SARS-CoV-2,

disaggregated by covariates (ie, household or family contact, index case

symptom status, adult or child contacts, contact sex, relationship to index

case, adult or child index cases, index case sex, number of contacts in

household) and for other coronaviruses.

Results A total of 54 relevant studies with 77 758 participants reporting

household secondary transmission were identified. Estimated household

secondary attack rate was 16.6% (95% Cl, 14.0%-19.3%), higher than

secondary attack rates for SARS-CoV (7.5%; 95% Cl, 4.8%-10.7%) and

MERS-CoV (4.7%; 95% Cl, 0.9%-10.7%). Household secondary attack rates

were increased from symptomatic index cases (18.0%; 95% Cl,

14.2%-22.1%) than from asymptomatic index cases (0.7%; 95% Cl,

0%-4.9%), to adult contacts (28.3%; 95% Cl, 20.2%-37.1%) than to child

contacts (16.8%; 95% Cl, 12.3%-21.7%), to spouses (37.8%; 95% Cl,

25.8%-50.5%) than to other family contacts (17.8%; 95% Cl, 11.7%-24.8%),

and in households with 1 contact (41.5%; 95% Cl, 31.7%-51.7%) than in

households with 3 or more contacts (22.8%; 95% Cl, 13.6%-33.5%). APPENDIX TO JAMES CASCIANO DECLARATION-129

Conclusions and Relevance The findings of this study suggest that given

that individuals with suspected or confirmed infections are being referred to

isolate at home, households will continue to be a significant venue for transmission of SARS-CoV-2.

Introduction

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe

acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread

via direct or indirect contact with infected people via infected respiratory

droplets or saliva, fomites, or aerosols.1,2 Crowded indoor environments

with sustained close contact and conversations, such as households, are a

particularly high-risk setting. 3

The World Health Organization China Joint Mission reported human-to

human transmission in China largely occurred within families, accounting for

78% to 85% of clusters in Guangdong and Sichuan provinces.4 Stay-at

home orders reduced human mobility by 35% to 63% in the United States, 5

63% in the United Kingdom,6 and 54% in Wuhan,7 relative to normal

conditions, which concomitantly increased time at home. Modeling studies

demonstrated that household transmission had a greater relative

contribution to the basic reproductive number after social distancing

(30%-55%) than before social distancing (5%-35%). 8 While current US

Centers for Disease Control and Prevention recommendations are to

maintain 6 feet of distance from a sick household member, this may be

difficult to achieve in practice and not be fully effective. 9

The household secondary attack rate characterizes virus transmissibility.

Studies can collect detailed data on type, timing, and duration of contacts

and identify risk factors associated with infectiousness of index cases and

susceptibility of contacts. Our objective was to estimate the secondary

attack rate of SARS-CoV-2 in households and determine factors that modify

this parameter. We also estimated the proportion of households with index

cases that had any secondary transmission. Furthermore, we compared the APPENDIX TO JAMES CASCIANO DECLARATION-130

SARS-CoV-2 household secondary attack rate with that of other severe

viruses and with that to close contacts for studies that reported the

secondary attack rate for both close and household contacts.

Methods

Definitions

We estimated the transmissibility of SARS-CoV-2 within the household or

family by the empirical secondary attack rate by dividing the number of new

infections among contacts by the total number of contacts. Household

contacts include anyone living in the same residence as the index case.

Family contacts include the family members of index cases, including

individuals who live outside the index case's household. Close contact

definitions varied by study and included physical proximity to an index case,

exceeding a minimum contact time, and/or not wearing effective protection

around index cases before the index case was tested.

Search Strategy

Following Preferred Reporting Items for Systematic Reviews and Meta

analyses (PRISMA) reporting guideline, we searched PubMed using terms

including SARS-CoV-2 or COVID-19 with secondary attack rate, household,

close contacts, contact transmission, contact attack rate, or family

transmission (eTable 1 in the Supplement) with no restrictions on language,

study design, time, or place of publication. The last search was conducted

October 19, 2020.

Eligibility Criteria

Eligibility criteria are described in eAppendix 1 in the Supplement. All

articles with original data for estimating household secondary attack rate

were included. Case reports focusing on individual households and studies

of close contacts that did not report secondary attack rates for household


members were excluded.

Data Extraction

One of us (Z.J.M.) extracted data from each study. Details appear in

eAppendix 2 in the Supplement.

Evaluation of Study Quality and Risk of Bias

To assess the methodological quality and risk of bias of included studies of

SARS-CoV-2, we used the same modified version of the Newcastle-Ottawa

quality assessment scale for observational studies used by Fung et al.10,11

Studies received as many as 9 points based on participant selection (4

points), study comparability (1 point), and outcome of interest (4 points).

Studies were classified as having high (~3 points), moderate (4-6 points),

and low (~7 points) risk of bias. One of us (Z.J.M.) evaluated the study

quality and assigned the quality grades.

Statistical Analysis

Meta-analyses were done using a restricted maximum-likelihood estimator

model to yield Freeman-Tukey double arcsine-transformed point estimates

and 95% Cl for secondary attack rate for each subgroup analyzed, with a

random effect for each study.12 For comparisons across covariates (ie,

household or family, index case symptom status, adult or child contacts,

contact sex, relationship to index case, adult or child index cases, index

case sex, number of household contacts, study location, universal or

symptomatic testing, dates of study) and comparisons with close contacts

and other viruses, study was treated as a random effect, and the covariate

was a fixed moderator. Variables had to have been collected in at least 3

studies to be included in meta-analyses. The Cochran Q test and /2 statistic

are reported as measures of heterogeneity. 12 values of 25%, 50%, and 75%

indicated low, moderate, and high heterogeneity, respectively.13 Stastistical

significance was set at a 2-tailed a= .05. All analyses were done in R version


4.0.2 using the package metafor (R Project for Statistical Computing). 14,15

When at least 10 studies were available, we used funnel plots, Begg

correlation, and Egger test to evaluate publication bias, with significance set

at P < .10.16•17 If we detected publication bias, we used the Duval and

Tweedie trim-and-fill approach for adjustment. 18

Results

We identified 54 relevant published studies that reported household

secondary transmission, with 77 758 participants (eTable 1 in the

Supplement). 19-72 A total of 16 of 54 studies (29.6%) were at high risk of

bias, 27 {50.0%) were moderate, and 11 (20.4%) were low {eTable 2 in the

Supplement). Lower quality was attributed to studies with 1 or fewer test

per contact (35 studies [64.8%]), small sample sizes (31 [57.4%]), and

secondary attack rate not disaggregated by covariates (28 [51.9%]).

A description of index case identification period and methods and symptom

status is provided in eTable 3 in the Supplement. Most studies did not

describe how co-primary index cases were handled or whether secondary

infections could have been acquired from outside the household, both of

which can inflate the empirical secondary attack rate. Testing and

monitoring strategies varied between studies, often reflecting variations in

local testing guidelines implemented as part of contact tracing (eTable 4

and eAppendix 3 in the Supplement).

Figure 1 summarizes secondary attack rates for 44 studies 19-26,28-30,32-

36·38-45,47-57,59,51-53,55-57,59,7o of household contacts and 10 of family

contacts. 26,31,37.45,58,60 ,65 ,68 ,71,72 Estimated mean secondary attack rate for

household contacts was 16.4% (95% Cl, 13.4%-19.6%) and family contacts

was 17.4% (95% Cl, 12.7%-22.5%). One study 40 restricted index cases to

children (age <18 years), resulting in a substantially lower secondary attack

rate of 0.5%. Excluding this outlier, the combined secondary attack rate for

household and family contacts was 17.1% (95%, 14.6%-19.7%). Secondary


attack rates for household and family contacts were more than 3 times

higher than for close contacts (4.8%; 95% Cl, 3.4%-6.5%; P < .001) (eFigure

2 in the Supplement). Significant heterogeneity was found among studies of

household (/2 = 96.9%; P < .001), family (/2 = 93.0%; P < .001), and close (/2 = 97.0%; P < .001) contacts. No significant publication bias was observed for studies of household, family, or close contacts (eFigure 3 in the

Supplement). Secondary attack rates were not significantly different when restricting to 38 studies 19,20,22,23,26-31,34-40,42,44-51,54-57,60,62,63,65,67-69,72

with low or moderate risk of bias (15.6%; 95%, 12.8%-18.5%) (eFigure 4 in

the Supplement). There were no significant differences in secondary attack rates between 21 studies in China22,27,31,36,37,39,45,46,48,58,61-68,70-72 and 33 studies from other countries 19-21,23-26,28-30,32-35,38,40-44,47,49-57,59,60,69

(eFigure 5 in the Supplement), 18 studies that tested symptomatic contacts 19-21,24,25,28,29,33,34,41,47,50,53,56,58,59,61,64 and 33 studies that

reported testing all contacts22,23,26,27,30,31,35-40,42-46,48,49,51,52,54,55,57,60,63,65-67,69-72 (eFigure 6 in the Supplement), and 16

early studies22,23,25,31,37,39,45,58,61,63-66,68,71,72 (January-February) and 20 later studies 19,24,26,29,30,32-35,38,42,44,50,53-56,59,60,69 (March-July) (eFigure

7 in the Supplement).

To study the transmissibility of asymptomatic SARS-CoV-2 index cases, eFigure 8 in the Supplement summarizes 27 studies19-21,23-26,30,32-34,44,45,47,50,52-54,56,59-61,63,64,68,69,72 reporting household secondary

attack rates from symptomatic index cases and 4 studies26,43A4,52 from

asymptomatic or presymptomatic index cases. Estimated mean household

secondary attack rate from symptomatic index cases (18.0%; 95% Cl, 14.2%-22.1%) was significantly higher than from asymptomatic or presymptomatic index cases (0.7%; 95% Cl, 0%-4.9%; P< .001), although there were few studies in the latter group. These findings are consistent with other household studies28,70 reporting asymptomatic index cases as having limited role in household transmission.

There is evidence for clustering of SARS-CoV-2 infections within


households, with some households having many secondary infections while

many others have none.73-75 For example, 1 study 55 reported that 26 of 103

(25.2%) households had all members test positive. This is consistent with

observation of overdispersion in the number of secondary cases per index

case across a range of settings. 3 While most studies reported only the

average number of secondary infections per index case, some also reported

transmission by household. 44,55,56,63,65,69 Figure 2 summarizes the

proportion of households with any secondary transmission. Using an

empirical analysis based on secondary attack rates and mean number of

contacts per household, we found the proportion of households with any

secondary transmission was lower than expected in a setting with no

clustering (eg, most transmission is not characterized by a minority of

infected individuals) (eTable 5 in the Supplement). Ideally, future studies will

assess this formally by fitting a J3 binomial to quantify overdispersion in the

full data.

A number of studies examined factors associated with susceptibility of

household contacts to infection (eTable 6 in the Supplement). Age was the most examined covariate with most studies 20,29,36-39,45,46,48,49,55,63,65,68

I

reporting lower secondary transmission of SARS-CoV-2 to child contacts

than adult contacts. In 5 studies, 2o,3s,39,4s,49 individuals older than 60

years were most susceptible to SARS-CoV-2 infection. Contact age was not

associated with susceptibility in 9 studies, 26,28,32A4A7,58,66,67,70 although

these were typically less powered to detect a difference. Figure 3 summarizes 15 studies22,26,29,37,39,42,44,45,47,49,55,59,60,63,65 reporting

separate secondary attack rates to children and adult contacts. The

estimated mean household secondary attack rate was significantly higher

to adult contacts (28.3%; 95% Cl, 20.2%-37.1%) than to child contacts

(16.8%; 95% Cl, 12.3%-21.7%; P < .001). Significant heterogeneity was found

among studies of adult (/2 = 96.8%; P < .001) and child contacts (/2 = 78.9%;

P < .001). Begg (P = .03) and Egger (P = .03) tests were statistically

significant for studies of adult but not child contacts (eFigure 9 in the

Supplement). One study of adults 63 had a high secondary attack rate in the APPENDIX TO JAMES CASCIANO DECLARATION-135

forest plot. Excluding this study improved the funnel plot symmetry and

resulted in a secondary attack rate to adult contacts of 26.3% (95% Cl, 19.3%-33.2%).

The second most examined factor was sex of exposed contacts, which was not associated with susceptibility for most studies20,22,26,32,36,39,4 4,4s,41-

49,59,65-57,7o except 3.38,46 ,68 eFigure 10 in the Supplement summarizes

results from 11 studies20,39 ,42 ,44 ,45 ,47,49 ,59 ,65 ,57,59 reporting household

secondary attack rates by contact sex. Estimated mean household

secondary attack rate to female contacts (20.7%; 95% Cl, 15.0%-26.9%) was not significantly different than to male contacts (17.7%; 95% Cl, 12.4%-23.8%). Significant heterogeneity was found among studies of

female contacts (12 = 87.4%; P< .001) and male contacts (12 = 87.7%; P

< .001). Moderate asymmetry was observed in the funnel plots, which was significant for studies of female contacts from Egger test (P = .07) but not male contacts (eFigure 11 in the Supplement). However, imputation of an

adjusted effect size using the trim-and-fill method did not significantly change the secondary attack rate to female contacts (19.7%; 95% Cl, 13.9%-25.6%).

Spouse relationship to index case was associated with secondary infection in 4 studies26,45A6,58 of 6 in which this was examined.65,67 Infection risk

was highest for spouses, followed by nonspouse family members and other

relatives, which were all higher than other contacts.46 Figure 4 summarizes results from 7 studies26,44 -46 ,58,65 ,67 reporting household secondary attack

rates by relationship. Estimated mean household secondary attack rate to spouses (37.8%; 95% Cl, 25.8%-50.5%) was significantly higher than to other contacts (17.8%; 95% Cl, 11.7%-24.8%). Significant heterogeneity was

found among studies of spouses (12 = 78.6%; P < .001) and other relationships (12 = 83.5%; P< .001).

Several studies examined factors associated with infectiousness of index cases. Older index case age was associated with increased secondary


infections in 3 studies 20A7,67 of 9 in which this was

examined. 22,36,39,44 ,63,65 eFigure 12 in the Supplement summarizes results

from 3 studies 42,44,51 reporting household secondary attack rates by index

case age. Estimated mean household secondary attack rate from adults

(15.2%; 95% Cl, 6.2%-27.4%) was not significantly different than that from

children (7.9%; 95% Cl, 1.7%-16.8%). Index case sex was associated with

transmission in 3 studies 42A4,67 of 9 in which this was

examined. 20,35,45,47,53,a5 eFigure 13 in the Supplement summarizes results

from 7 studies 20A2A4A5,65,67,69 reporting household secondary attack rates

by index case sex. Estimated mean household secondary attack rate from

female contacts (16.6%; 95% Cl, 11.2%-22.8%) was not significantly

different than from male contacts (16.4%; 95% Cl, 9.0%-25.5%).

Critically severe index case symptoms was associated with higher

infectiousness in 6 studies 20,38,46-48 ,67 of 9 in which this was

examined. 44 ,63,70 Index case cough was associated with infectivity in 2

studies 20,65 of 8 in which this was examined 45-48,63,67 (eAppendix 4 in the

Supplement).

Contact frequency with the index case was associated with higher odds of

infection, specifically at least 5 contacts during 2 days before the index

case was confirmed, 70 at least 4 contacts and 1 to 3 contacts, 63 or frequent

contact within 1 meter.22,67,68 Smaller households were associated with

transmission in 4 studies 20,39,47,49 of 7 in which this was examined. 55,63,65

Figure 5 summarizes results from 6 studies 20,47,49 ,55,s1,65 reporting

household secondary attack rates by number of contacts in the household.

Estimated mean household secondary attack rate for households with 1

contact (41.5%; 95% Cl, 31.7%-51.7%) was significantly higher than

households with at least 3 contacts (22.8%; 95% Cl, 13.6%-33.5%; P< .001)

but not different than households with 2 contacts (38.6%; 95% Cl,

17.9%-61.6%). There was significant heterogeneity in secondary attack

rates between studies with 1 contact (/2 = 52.9%; P = .049), 2 contacts (/2 =

93.6%; P< .001), or 3 or more contacts (/2 = 91.6%; P< .001). Information


was not available on household crowding (eg, number of people per room).

eFigure 14 in the Supplement summarizes 7 studies 76-82 reporting

household secondary attack rates for SARS-CoV, and 7 studies 83-89 for

Middle East respiratory syndrome coronavirus (MERS-CoV). Estimated

mean household secondary attack rate was 7.5% (95% Cl, 4.8%-10.7%) for

SARS-CoV and 4.7% (95% Cl, 0.9%-10.7%) for MERS-CoV (eTable 7 in the

Supplement), both lower than the household secondary attack rate of

16.6% for SARS-CoV-2 in this study (P < .001). The SARS-CoV-2 secondary

attack rate was also higher than secondary attack rates reported for HCoV

NL63 (0-12.6%), HCoV-OC43 (10.6-13.2%), HCoV-229E (7.2-14.9%), and

HCoV-HKU1 (8.6%).90-92 Household secondary attack rates for SARS-CoV-

2 were within the mid-range of household secondary attack rates reported

for influenza, which ranged from 1% to 38% based on polymerase chain

reaction-confirmed infection. 93

Discussion

We synthesized the available evidence on household studies of SARS-CoV-

2. The combined household and family secondary attack rate was 16.6%

(95% Cl, 14.0%-19.3%), although with significant heterogeneity between

studies. This point estimate is higher than previously observed secondary

attack rates for SARS-CoV and MERS-CoV. Households are favorable

environments for transmission. They are what are known as 3Cs

environments, as they are closed spaces, where family members may crowd

and be in close contact with conversation. 94 There may be reduced use of

personal protective equipment relative to other settings.

That secondary attack rates were not significantly different between

household and family contacts may indicate that most family contacts are in

the same household as index cases. Household and family contacts are at

higher risk than other types of close contacts, and risks are not equal within

households. Spouses were at higher risk than other family contacts, which

may explain why the secondary attack rate was higher in households with 1 APPENDIX TO JAMES CASCIANO DECLARATION-138

vs 3 or greater contacts. Spouse relationship to the index case was also a

significant risk factor observed in studies of SARS-CoV and H1N1.82 ,95 This

may reflect intimacy, sleeping in the same room, or longer or more direct

exposure to index cases. Further investigation is required to determine

whether sexual contact is a transmission route. Although not directly

assessed, household crowding (eg, number of people per room) may be

more important for SARS-CoV-2 transmission than the total number of

people per household, as has been demonstrated for influenza. 96-98

The finding that secondary attack rates were higher to adult contacts than

to child contacts is consistent with empirical and modeling studies. 99 ,100

Lower infection rates in children may be attributed to asymptomatic or mild

disease, reduced susceptibility from cross-immunity from other

coronaviruses, 101 and low case ascertainment, 102 but the difference

persisted in studies in which all contacts were tested regardless of

symptoms. Higher transmission rates to adults may be influenced by

spousal transmission. Given the increased risk to spousal contacts, future

studies might compare child contacts and nonspouse adult contacts to

ascertain whether this difference persists. Limited data suggest children

have not played a substantive role in household transmission of SARS-CoV-

2. 40, 103-105 However, a study in South Korea of 10 592 household contacts

noted relatively high transmission from index cases who were aged 10 to 19

years.51 Although children seem to be at reduced risk for symptomatic

disease, it is still unclear whether they shed virus similarly to adults. 106

We did not find associations between household contact or index case sex

and secondary transmission. The World Health Organization reports roughly

even distribution of SARS-CoV-2 infections between women and men

worldwide, with higher mortality in men.107

We found significantly higher secondary attack rates from symptomatic

index cases than asymptomatic or presymptomatic index cases, although

less data were available on the latter. The lack of substantial transmission


from observed asymptomatic index cases is notable. However,

presymptomatic transmission does occur, with some studies reporting the

timing of peak infectiousness at approximately the period of symptom

onset. 108,109 In countries where infected individuals were isolated outside

the home, this could further alter the timing of secondary infections by

limiting contacts after illness onset. 110

Household secondary attack rates were higher for SARS-CoV-2 than SARS

CoV and MERS-CoV, which may be attributed to structural differences in

spike proteins, 111 higher basic reproductive rates, 112 and higher viral loads in

the nose and throat at the time of symptom onset. 113 Symptoms associated

with MERS-CoV and SARS-CoV often require hospitalization, which

increases nosocomial transmission, whereas less severe symptoms of

SARS-CoV-2 facilitate community transmission. 113 Similarly,

presymptomatic transmission was not observed for MERS-CoV or SARSCov.114, 115

Limitations

Our study had several limitations. The most notable is the large amount of

unexplained heterogeneity across studies. This is likely attributable to

variability in study definitions of index cases and household contacts,

frequency and type of testing, sociodemographic factors, household

characteristics (eg, density, air ventilation), and local policies (eg,

centralized isolation). Rates of community transmission also varied across

locations. Given that studies cannot always rule out infections from outside

of the home (eg, nonhousehold contacts), household transmission may be

overestimated. For this reason, we excluded studies that used antibody

tests to diagnose household contacts. Furthermore, many analyses ignored

tertiary transmission within the household, classifying all subsequent cases

as secondary to the index case. Eighteen studies 19-21,24,25,28,29,33,34,41,47,50,53,56,58,59,61,64 involved testing only symptomatic

household contacts, which would miss asymptomatic or subclinical


infections, although secondary attack rate estimates were similar across

studies testing all vs only symptomatic contacts.

Important questions remain regarding household spread of SARS-CoV-2.

Chief among them is the infectiousness of children to their household

contacts and the infectiousness of asymptomatic, mildly ill, and severely ill

index cases. This study did not provide additional elucidation of factors

influencing intergenerational spread. People unable to work at home may

have greater risk of SARS-CoV-2 exposure, which may increase

transmission risk to other household members. There may be

overdispersion in the number of secondary infections per index case, which

could be caused by variations in viral shedding, household ventilation, or

other factors.

Conclusions

The findings of this study suggest that households are and will continue to

be important venues for transmission, even where community transmission

is reduced. Prevention strategies, such as increased mask-wearing at

home, improved ventilation, voluntary isolation at external facilities, and

targeted antiviral prophylaxis, should be further explored.

Back to top

Article Information

Accepted for Publication: November 6, 2020.

Published: December 14, 2020. doi:10.1001/jamanetworkogen.2020.31756

Open Access: This is an open access article distributed under the terms of

the CC-BY License. © 2020 Madewell ZJ et al. JAMA Network Open.

Corresponding Author: Zachary J. Madewell, Department of Biostatistics,

University of Florida, PO Box 117450, Gainesville, FL 32611


{[email protected]).

Author Contributions: Drs Madewell and Dean had full access to all of the

data in the study and take responsibility for the integrity of the data and the

accuracy of the data analysis.

Concept and design: Madewell, Longini, Dean.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Madewell, Longini, Dean.

Critical revision of the manuscript for important intellectual content: All

authors.

Statistical analysis: All authors.

Obtained funding: Dean.

Administrative, technical, or material support: Dean.

Supervision: Dean.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by grant R01-Al139761 from

the National Institutes of Health.

Role of the Funder/Sponsor: The funder had no role in the design and

conduct of the study; collection, management, analysis, and interpretation

of the data; preparation, review, or approval of the manuscript; and decision

to submit the manuscript for publication.

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Post-lockdown SARS-CoV-2 nucleic acid screening in nearly ten million residents of Wuhan, China , 20 November 2020

Nature Communications 11, Article number: 5917 (2020) Cite this article

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Abstract

Stringent COVID-19 control measures were imposed in Wuhan between

January 23 and April 8, 2020. Estimates of the prevalence of infection

following the release of restrictions could inform post-lockdown pandemic

management. Here, we describe a city-wide SARS-CoV-2 nucleic acid

screening programme between May 14 and June 1, 2020 in Wuhan. All city

residents aged six years or older were eligible and 9,899,828 (92.9%)

participated. No new symptomatic cases and 300 asymptomatic cases

(detection rate 0.303/10,000, 95% Cl 0.270-0.339/10,000) were identified.

There were no positive tests amongst 1,174 close contacts of asymptomatic

cases. 107 of 34,424 previously recovered COVID-19 patients tested

positive again (re-positive rate 0.31%, 95% Cl 0.423-0.574%). The

prevalence of SARS-CoV-2 infection in Wuhan was therefore very low five


to eight weeks after the end of lockdown.

Introduction

The Coronavirus Disease 2019 {COVID-19) was first reported in December

2019, and was classified as a pandemic by the World Health Organization

on March 11, 2020 1. Following strict lockdown measures, the COVID-19

epidemic was generally under control in China, and the whole country has

progressed into a post-lockdown phase. In this phase, countries face new

problems and challenges, including how to accurately assess the post

lockdown risk of the COVID-19 epidemic, how to avoid new waves of

COVID-19 outbreaks, and how to facilitate the resumption of economy and

normal social life. As the city most severely affected by COVID-19 in China,

Wuhan had been under lockdown measures from January 23 until April 8,

2020. During the first 2 months after city's reopening, there were only a few

sporadic COVID-19 cases in Wuhan {six newly confirmed cases from April 8

to May 10, 2020 2). However, there was still concern about the risk of

COVID-19 in Wuhan, which seriously affected the resumption of industrial

production and social services, and hampered the normal lives of residents.

In order to ascertain the current status of the COVID-19 epidemic, the city

government of Wuhan carried out a comprehensive citywide nucleic acid

screening of SARS-CoV-2 infection from May 14, 2020 to June 1, 2020.

The citywide screening of SARS-CoV-2 infection in Wuhan is a mass

screening programme in post-lockdown settings, and provided invaluable

experiences or lessons with international relevance as more countries and

cities around the world entering the post-lockdown phase. In this study, we

report the organisation process, detailed technical methods used, and

results of this citywide nucleic acid screening.

Results

There were 10,652,513 eligible people aged :?:6 years in Wuhan (94.1% of


the total population). The nucleic acid screening was completed in 19 days

(from May 14, 2020 to Jun 1, 2020), and tested a total of 9,899,828 persons

from the 10,652,513 eligible people (participation rate, 92.9%). Of the

9899,828 participants, 9,865,404 had no previous diagnosis of COVID-19,

and 34,424 were recovered COVID-19 patients.

The screening of the 9,865,404 participants without a history of COVID-19

found no newly confirmed COVID-19 cases, and identified 300

asymptomatic positive cases with a detection rate of 0.303 (95% Cl 0.270-

0.339)/10,000. The median age-stratified Ct-values of the asymptomatic

cases were shown in Supplementary Table 1. Of the 300 asymptomatic

positive cases, two cases came from one family and another two were from

another family. There were no previously confirmed COVID-19 patients in

these two families. A total of 1174 close contacts of the asymptomatic

positive cases were traced, and they all tested negative for the COVID-19.

There were 34,424 previously recovered COVID-19 cases who participated

in the screening. Of the 34,424 participants with a history of COVID-19, 107

tested positive again, giving a repositive rate of 0.310% (95% Cl 0.423-

0.574%).

Virus cultures were negative for all asymptomatic positive and repositive

cases, indicating no "viable virus" in positive cases detected in this study.

All asymptomatic positive cases, repositive cases and their close contacts

were isolated for at least 2 weeks until the results of nucleic acid testing

were negative. None of detected positive cases or their close contacts

became symptomatic or newly confirmed with COVID-19 during the

isolation period. In this screening programme, single and mixed testing was

performed, respectively, for 76.7% and 23.3% of the collected samples. The

asymptomatic positive rates were 0.321 (95% Cl 0.282-0.364)/10,000 and

0.243 (95% Cl 0.183-0.315)/10,000, respectively.

The 300 asymptomatic positive persons aged from 10 to 89 years, included

132 males (0.256/10,000) and 168 females (0.355/10,000). The APPENDIX TO JAMES CASCIANO DECLARATION-163

asymptomatic positive rate was the lowest in children or adolescents aged

17 and below (0.124/10,000), and the highest among the elderly aged 60

years and above (0.442/10,000) (Table 1). The asymptomatic positive rate in

females (0.355/10,000) was higher than that in males (0.256/10,000).

Table 1 Characteristics of asymptomatic positive individuals.

Full size table

The asymptomatic positive cases were mainly domestic and unemployed

residents (24.3%), retired older adults (21.3%), and public service workers

(11.7%} (Fig.1).

Fig. 1: The occupation distribution of asymptomatic positive cases(%).

2,0.7%

4, 1.3%

■ Housework or unemployment

The emeritus and retirees

Service workers in public place

Industrial labourer

■ Cadres staff

■ Agricultural labourer

■ Student

■ Teacher

■ Medical staff

■ Transportation service personnel

■ Others

Note: Others included the self-employed, military personnel, and so on. (Source data are provided

ass Source Data file.).

Full size imagg

The asymptomatic positive rate in urban districts was on average

0.456/10,000, ranging from 0.317/10,000 in Hongshan to 0.807/10,000 in

Wuchang district. A lower rate of asymptomatic positive cases was found in

suburban districts (0.132/10,000), ranging from 0.047/10,000 in Xinzhou to

0.237/10,000 in Jiangan district (Fig. 2).


Fig. 2: The geographic distribution of the detection rate of asymptomatic positive cases.

,,r

;

Celdlan

0.218

Dollplhu OJll4

Huangpl 0.143

Jiangxla 0.209

., .

• East Lake Hia,Hec:h Development Zone

G.143

Xlnlhou OJM7

0 10Km

Detection rate of asymptomatic patients at District level (per 10.000)

JI{:,:.>--"----...... ;;,r'' "\I"\_ I.

11110.000

0.001--0.100

0.101--0.200

0.201--0.300

0.301--0.400

11110.401--0.600

11110.601--0.750

Note: 1 represents Jianghan district; 2 represents Qiaokou district. (Source data are provided as s

Source Data file.).

Full size imag~

Among the 7280 residential communities in Wuhan, asymptomatic positive


cases were identified in 265 (3.6%) communities (only one case detected in

246 communities), while no asymptomatic positive cases were found in other 96.4% communities.

Testing of antibody against SARS-CoV-2 virus was positive lgG (+) in 190 of

the 300 asymptomatic cases, indicating that 63.3% (95% Cl 57.6-68.8%) of

asymptomatic positive cases were actually infected. The proportion of

asymptomatic positive cases with both lgM (-) and lgG (-) was 36.7% {95%

Cl: 31.2-42.4%; n = 110), indicating the possibility of infection window or

false positive results of the nucleic acid testing (Table 2).

Table 2 Results of the detection of antibody in 300 asymptomatic positive persons.

Full size table

Higher detection rates of asymptomatic infected persons were in Wuchang,

Qingshan and Qiaokou districts, and the prevalence of previously confirmed

COVID-19 cases were 68.243/10,000, 53.767/10,000, and 100.047/10,000,

respectively, in the three districts. Figure .3 shows that districts with a high

detection rate of asymptomatic positive persons generally had a high

prevalence of confirmed COVID-19 cases {rs= 0.729, P = 0.002).

Fig. 3: The prevalence of previously confirmed patients and the detection rate of asymptomatic positive

cases of COVID-19 in each district in Wuhan.


a

I c......, ~8 en o ::Jr-2 ... i& a.~ 'oi GI·-g-GI 8_ cij

~ a.

b

120.000

100.000

80.000

60.000

40.000

20.000

0.900

0.800

.!:! 0.700 'i E-%8 0.600

[~ ~-= 0.500 0 g_ ti o.4oo ~u 0 .E 0300 ~ 5: .

~ 0.200

0.100

100.047

0.807

0.000

a The prevalence of previously confirmed patients of COVID-19 in each district in Wuhan. b The

detection rate of asymptomatic positive cases of COVID-19 in each district in Wuhan. (Source data

are provided ass Source Data file.).

Full size imag~


Discussion

The citywide nucleic acid screening of SARS-CoV-2 infection in Wuhan

recruited nearly 10 million people, and found no newly confirmed cases with

COVID-19. The detection rate of asymptomatic positive cases was very low,

and there was no evidence of transmission from asymptomatic positive

persons to traced close contacts. There were no asymptomatic positive

cases in 96.4% of the residential communities.

Previous studies have shown that asymptomatic individuals infected with

SARS-CoV-2 virus were infectious~, and might subsequently become

symptomatic~. Compared with symptomatic patients, asymptomatic

infected persons generally have low quantity of viral loads and a short

duration of viral shedding, which decrease the transmission risk of SARS

CoV-2'Q.. In the present study, virus culture was carried out on samples from

asymptomatic positive cases, and found no viable SARS-CoV-2 virus. All

close contacts of the asymptomatic positive cases tested negative,

indicating that the asymptomatic positive cases detected in this study were

unlikely to be infectious.

There was a low repositive rate in recovered COVID-19 patients in Wuhan.

Results of virus culturing and contract tracing found no evidence that

repositive cases in recovered COVID-19 patients were infectious, which is

consistent with evidence from other sources. A study in Korea found no

confirmed COVID-19 cases by monitoring 790 contacts of 285 repositive

cases2. The official surveillance of recovered COVID-19 patients in China

also revealed no evidence on the infectiousness of repositive cases2.

Considering the strong force of infection of COVID-198,9,10, it is expected

that the number of confirmed cases is associated with the risk of being

infected in communities. We found that asymptomatic positive rates in

different districts of Wuhan were correlated with the prevalence of

previously confirmed cases. This is in line with the temporal and spatial

evolution (especially the long-tailed characteristic) of infectious diseases11.


Existing laboratory virus culture and genetic studies.9,10 showed that the

virulence of SARS-CoV-2 virus may be weakening over time, and the newly

infected persons were more likely to be asymptomatic and with a lower viral

load than earlier infected cases. With the centralized isolation and

treatment of all COVID-19 cases during the lockdown period in Wuhan, the

risk of residents being infected in the community has been greatly reduced.

When susceptible residents are exposed to a low dose of virus, they may

tend to be asymptomatic as a result of their own immunity. Serological

antibody testing in the current study found that at least 63% of

asymptomatic positive cases were actually infected with SARS-CoV-2 virus.

Nonetheless, it is too early to be complacent, because of the existence of

asymptomatic positive cases and high level of susceptibility in residents in

Wuhan. Public health measures for the prevention and control of COVID-19

epidemic, including wearing masks, keeping safe social distancing in Wuhan

should be sustained. Especially, vulnerable populations with weakened

immunity or co-morbidities, or both, should continue to be appropriately

shielded.

Findings from this study show that COVID-19 was well controlled in Wuhan

at the time of the screening programme. After two months since the

screening programme (by August 9, 2020), there were no newly confirmed

COVID-19 cases in Wuhan. Further testing of SARS-CoV-2 in samples

collected from market environment settings in Wuhan were conducted, and

found no positive results after checking a total of 52,312 samples from 1795

market setting during June 13 to July 2, 2020 12•

This study has several limitations that need to be discussed. First, this was

a cross-sectional screening programme, and we are unable to assess the

changes over time in asymptomatic positive and reoperative results.

Second, although a positive result of nucleic acid testing reveals the

existence of the viral RNAs, some false negative results were likely to have

occurred, in particular due to the relatively low level of virus loads in

asymptomatic infected individuals, inadequate collection of samples, and


limited accuracy of the testing technology 13• Although the screening

programme provided no direct evidence on the sensitivity and specificity of

the testing method used, a meta-analysis reported a pooled sensitivity of

73% (95% Cl 68-78%) for nasopharayngeal and throat swab testing of

COVID-1914• Testing kits used in the screening programme were publicly

purchased by the government and these kits have been widely used in

China and other countries. Multiple measures were taken to possibly

minimise false negative results in the screening programme. For example,

standard training was provided to health works for sample collection to

ensure the sample quality. The experiment procedures, including specimen

collection, extraction, PCR, were according to official guidelines

(Supplementary Note 1). For the real-time RT-PCR assay, two target genes

were simultaneously tested. Even so, false negative results remained

possible, particularly in any mass screening programmes. However, even if

test sensitivity was as low as 50%, then the actual prevalence would be

twice as high as reported in this study, but would still be very low. Around

7.1% of eligible residents did not participate in the citywide nucleic acid

screening and the screening programme did not collect detailed data on

reasons for nonparticipation, which is a limitation of this study. Although

there were no official statistics, a large number of migrant workers and

university students left Wuhan before the lockdown, joining their families in

other cities or provinces for traditional Chinese New Year. Therefore, it is

likely that most nonparticipants were not in Wuhan at the time of the

screening. The main objective of the screening programme was to assess

the risk of COVID-19 epidemic in residents who were actually living in the

post-lockdown Wuhan. Therefore, the estimated positive rates are unlikely

to be materially influenced by nonparticipation of residents who were not in

Wuhan or some residents who did not participate in the screening for other

reasons. Moreover, people who left Wuhan were the target population for

monitoring in other provinces and cities and were required to take nucleic

acid testing. Although there was no official statistics showing the positive

rate of nucleic acid testing in this population, there was no report that


shown a higher positive rate of nucleic acid testing than our findings.

In summary, the detection rate of asymptomatic positive cases in the postlockdown Wuhan was very low (0.303/10,000), and there was no evidence that the identified asymptomatic positive cases were infectious. These findings enabled decision makers to adjust prevention and control strategies in the post-lockdown period. Further studies are required to fully evaluate the impacts and cost-effectiveness of the citywide screening of SARS-CoV-2 infections on population's health, health behaviours, economy, and society.

Methods

Study population and ethical approvals

Wuhan has about 11 million residents in total, with seven urban and eight suburban districts. Residents are living in 7280 residential communities (or residential enclosures, "xiao-qu" in Chinese), and each residential community could be physically isolated from other communities for preventing transmission of COVID-19.

The screening programme recruited residents (including recovered COVID-19 patients) currently living in Wuhan who were aged ~6 years (5,162,960 males, 52.2%). All participants provided written or verbal informed consent after reading a statement that explained the purpose of the testing. For participants who aged 6-17 years old, consent was obtained from their parents or guardians. The study protocol for an evaluation of the programme based on anonymized screening data was approved by the Ethics Committee of the Tongji Medical College Institutional Review Board, Huazhong University of Science and Technology, Wuhan, China (No.

IROG0003571).

Organizational guarantee and community mobilization


A citywide nucleic acid screening group was formed, with specialized task

teams contributing to comprehensive coordination, technical guidance,

quality control, participation invitation, information management,

communication, and supervision of the screening. The city government

invested 900 million yuan (RMB) in the testing programme. From 14 May to

1 June 2020, in the peak time, up to 2907 sample collection sites were

functioning at the same time in Wuhan. Each sample collection site had an

assigned sample collection group, including several health professionals

(staffed according to the number of communities' residents), 2-4 community managers, 1-2 police officers, and 1-2 inspectors. The sampling

sites were set up based on the number and accessibility of local residents.

Local community workers were responsible for a safe and orderly sampling

process to minimise the waiting time. In addition, mobile sampling teams

were formed by primary health care professionals and volunteers to

conduct door-to-door sampling for residents who had physical difficulties

or were unable to walk.

About 50,000 health professionals (mainly doctors and nurses from

community health centers) and more than 280,000 person-times of

community workers and volunteers contributed to sample collection,

transport of equipment and samples collected, arrangement of participation

process, and maintaining order of sampling sites. Public information

communication and participant invitation were implemented through mass

media, mobile messages, WeChat groups, and residential community

broadcasts, so as to increase residents' awareness and the participation.

Acquisition, preservation, and transport of samples

All sampling personnel received standard training for the collection of

oropharyngeal swab samples. To minimise the risk of cross-infection, the

sampling process strictly followed a disinfection process and environmental

ventilation were ensured. The collected samples were stored in a virus

preservation solution or immersed in isotonic saline, tissue culture solution,


or phosphate buffer (Supplementary note 1). Then, all samples were sent to

testing institutions within 4 h using delivery boxes for biological samples

refrigerated with dry ice to guarantee the stability of nucleic acid samples.

Technical methods for laboratory testing of collected samples

A total of 63 nucleic acid testing laboratories, 1451 laboratory workers and

701 testing equipment were involved in the nucleic acid testing. Received

samples were stored at 4 °C and tested within 24 h of collection. Any

samples that could not be tested within 24 h were stored at - 70 °C or below

(Supplementary note 1). In addition to "single testing" (i.e., separate testing

of a single sample), "mixed testing" was also performed for 23% of the

collected samples to increase efficiency, in which five samples were mixed

in equal amounts, and tested in the same test tube. If a mixed testing was

positive for COVID-19, all individual samples were separately retested within

24 h 15•

Details regarding technical methods for sequencing and virus culture were

provided in Supplementary note 1. Real-time reverse transcriptase

polymerase chain reaction (RT-PCR) assay method was used for the nucleic

acid testing. We simultaneously amplified and tested the two target genes:

open reading frame 1ab (ORF1ab) and nucleocapsid protein (N)

(Supplementary Note 1). A cycle threshold value (Ct-value) less than 37

was defined as a positive result, and no Ct-value or a Ct-value of 40 or

more was defined as a negative result. For Ct-values ranging from 37 to 40,

the sample was retested. If the retest result remained less than 40 and the

amplification curve had obvious peak, the sample was classified as positive;

otherwise, it was reported as being negative. These diagnostic criteria were

based on China's official recommendations 16•

For asymptomatic positive cases, virus culture was carried out in biosafety

level-3 laboratories. The colloidal gold antibody test was also performed for


asymptomatic positive cases {Supplementary note 1). All testing results

were double entered into a specifically designed database, and managed by

the Big Data and Investigation Group of the COVID-19 Prevention and

Control Centre in Wuhan, which was established to collect and manage

data relevant to the COVID-19 epidemic.

Participant data collection and management

Before sample collection, residents electronically {using a specifically

designed smartphone application) self-uploaded their personal information,

including ID number, name, sex, age, and place of residence. Then, the

electronic machine system generated a unique personal barcode and stuck

it on the sample tube to ensure the match between the sample and the

participant. Then trained staff interviewed each individual regarding the

history of COVID-19 and previous nucleic acid testing. There was a

database of confirmed COVID-19 cases in Wuhan, which can be used to

validate the self-reported previous COVID-19 infection. All information was

entered into a central database. The testing results were continually

uploaded to the central database by testing institutions. Contact tracing

investigations were conducted on participants who tested positive for

SARS-CoV-2, to track and manage their close contacts. The pre-existing

unique identification code for each resident was used as the programme's

identification number, to ensure information accuracy during the whole

process of screening, from sampling, nucleic acid testing, result reporting,

the isolation of detected positive cases, and tracing of close contacts of

positive cases. All screening information was kept strictly confidential and

was not allowed to be disclosed or used for other purposes other than

clinical and public health management. Personal information of

asymptomatic positive cases was only disclosed to designated medical

institutions and community health centres for the purpose of medical

isolation and identification of close contacts. Researcher was blind to the

study hypothesis during data collection.


Biological security guarantee

Nucleic acid testing was performed in biosafety level-2 (BSL-2)

laboratories, and virus culture was conducted in biosafety level-3

laboratories. Sampling and testing personnel adopted the personal

protective measures according to the standard of biosafety level-3

laboratories. Participating laboratories implemented control measures to

guarantee biological safety in accordance with relevant regulations 17•

Result query and feedback

Two to three days after sample collection, participants could inquire about

their test results using WeChat or Alipay application by their unique ID

numbers. The results included text descriptions of nucleic acid testing and

coloured health codes. A green coloured health code refers to a negative

result, and a red coloured health code indicates a positive result.

Definition and management of identified confirmed cases and close contacts

In this study, all confirmed COVID-19 cases were diagnosed by designated

medical institutions according to National Guidelines for the Prevention and

Control of COVID-19 (Supplementary Note 2). Asymptomatic positive cases

referred to individuals who had a positive result during screening, and they

had neither a history of COVID-19 diagnosis, nor any clinical symptoms at

the time of the nucleic acid testing. Close contacts were individuals who

closely contacted with an asymptomatic positive person since 2 days

before the nucleic acid sampling 16• Repositive cases refer to individuals who

recovered from previously confirmed COVID-19 disease and had a positive

testing again in the screening programme. All repositive cases,

asymptomatic positive persons, and their close contacts were isolated for at

least 2 weeks in designated hotels managed by primary health care

professionals, and they were released from isolation only if two consecutive


nucleic acid tests were negative.

Statistical analysis

Detection rate of asymptomatic positive or repositive cases was calculated

by dividing the number of individuals with a positive result of nucleic acid

testing by the number of participants tested. Because of extremely low

detection rates, we calculated 95% confidence intervals of estimated

proportions using Pearson-Klapper exact method, implemented through R

package "binom" version 1.1-118• SPSS version 22.0 was used for other

statistical analyses. We analyzed the distribution of asymptomatic positive

cases and assessed the Spearman correlation between the asymptomatic

positive rate and the prevalence of previously confirmed COVID-19 cases in

different districts of Wuhan. Differences in asymptomatic positive rates by

sex and age groups were assessed using the x2 test. ArcGIS 10.0 was used

to draw a geographic distribution map of asymptomatic positive cases. A

value of P < 0.05 (two-tailed) was considered statistically significant.

Reporting summary

Further information on research design is available in the Nature Research

ReP-orting Summary linked to this article.

Data availability

Detailed data directly used to generate each figure or table of this study are

available within the article, SupplementarY. Information andsource data are

provided with this paper.

Change history

17 December 2020

The original version of this Article was updated shortl}! after publication,


because the Peer Review file was inadvertently omitted. The error has now

been fixed and the Peer Review file is available to download from the HTML version of the Article.

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Acknowledgements

We would like to thank all institutions and all citizens in Wuhan for their

support for citywide nucleic acid screening work. We also would like to

thank the Wuhan city government for this citywide nucleic acid testing,

sampling and management, and thank the big data and investigation group

of COVID-19 prevention and control institution in Wuhan (the data and

investigation group of Wuhan Municipal Health Commission) for their efforts

in the data collection. In addition, we would like to thank the National Social

Science Foundation of China (Grant No. 18ZDA085) for supporting the

fund.

Author information


These authors contributed equally: Shiyi Cao, Yong Gan, Chao Wang.

Affiliations

Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science

and Technology, Wuhan, Hubei, China

Shiyi Cao, Yong Gan, Chao Wang, Yuchai Huang, Tiantian Wang, Yanhong Gong, Hongbin Xu, Xin Shen, Xiaoxv Yin & Zuxun Lu

Norwich Medical School, Faculty of Medicine and Health Science, University of East Anglia, Norwich, UK

Max Bachmann & Fujian Song

Wuhan Municipal Health Commission, Wuhan, Hubei, China

Shanbo Wei

Wuhan Centre for Clinical Laboratory, Wuhan, Hubei, China

Jie Gong

Department of Management Science and Engineering, School of Economics and Management, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, China

Liqing Li

Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China

Kai Lu

Centre for Alcohol Policy Research, School of Psychology and Public


Health, La Trobe University, Melbourne, VIC, Australia

Heng Jiang

Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia

Heng Jiang

School of Public Health, Zhengzhou University, Zhengzhou, Henan, China

Qingfeng Tian

Department of Emergency, Hainan Clinical Research Centre for Acute and Critical Diseases, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China

Chuanzhu Lv

Contributions

S.Y.C., C.W., X.X.Y., and Z.X.L. conceived the study. C.W., Y.C.H., T.T.W., K.L.,

H.B.X., and X.S. participated in the acquisition of data. S.B.W. and J.G. were

responsible for the on-site specimen collection, laboratory testing quality

evaluation, and control. Y.C.H., T.T.W., and L.Q.L. analyzed the data. H.J.,

Y.H.G., and F.J.S. gave advice on methodology. Q.F.T. and C.Z.L.

investigated the responses to the citywide nucleic acid testing among

residents lived in outside of Wuhan city. S.Y.C., Y.G., C.W., and X.X.Y. drafted

the manuscript, Y.G., M.B., and F.J.S. revised the manuscript, and M.B.,

C.Z.L., and F.J.S. critically commented and edited the manuscript. All

authors read and approved the final manuscript. Z.X.L. is the guarantor of

this study.

Corresponding authors


Correspondence to Chuanzhu Lv or Fujian Song or Xiaoxv Yin or Zuxun Lu.

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The authors declare no competing interests.

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Guidance on Preparing Workplaces for COVID-19

OSHA 3990-03 2020


O)~ www.osha.gov

Occupational Safety and Health Act of 1970 11To assure safe and healthful working conditions for working men and women; by authorizing enforcement of the standards developed under the Act; by assisting and encouraging the States in their efforts to assure safe and healthful working conditions; by providing for research1 information, education, and training in the field of occupational safety and health."

This guidance is not a standard or regulation, and it creates no new legal obligations. It contains recommendations as well as descriptions of mandatory safety and health standards. The recommendations are advisory in nature, informational in content, and are intended to assist employers in providing a safe and healthful workplace. The Occupational Safety and Health Act requires employers to comply with safety and health standards and regulations promulgated by OSHA or by a state with an OSHA-approved state plan. In addition, the Act's General Duty Clause, Section 5(a)(1 ), requires employers to provide their employees with a workplace free from recognized hazards likely to cause death or serious physical harm.

Material contained in this publication is in the public domain and may be reproduced, fully or partially, without permission. Source credit is requested but not required.

This information will be made available to sensoryimpaired individuals upon request. Voice phone: (202) 693-1999; teletypewriter (TTY) number: 1-877-889-5627.


Guidance on Preparing Workplaces for COVID-19

U.S. Department of Labor Occupational Safety and Health Administration

OSHA 3990-03 2020

U.S. Department of Labor


Contents

Introduction .......................................... 3

About COVID-19 ....................................... 4

How a COVID-19 Outbreak Could Affect Workplaces ........ 6

Steps All Employers Can Take to Reduce Workers' Risk of Exposure to SARS-CoV-2 ................. 7

Classifying Worker Exposure to SARS-CoV-2 .............. 18

Jobs Classified at Lower Exposure Risk (Caution): What to Do to Protect Workers .......................... 20

Jobs Classified at Medium Exposure Risk: What to Do to Protect Workers .......................... 21

Jobs Classified at High or Very High Exposure Risk: What to Do to Protect Workers .......................... 23

Workers Living Abroad or Travelling Internationally ........ 25

For More Information .................................. 26

OSHA Assistance, Services, and Programs ............... 27

OSHA Regional Offices ................................ 29

How to Contact OSHA ................................. 32


Introduction Coronavirus Disease 2019 (COVID-19) is a respiratory disease caused by the SARS-CoV-2 virus. It has spread from China to many other countries around the world, including the United States. Depending on the severity of COVID-19's international impacts, outbreak conditions-including those rising to the level of a pandemic-can affect all aspects of daily life, including travel, trade, tourism, food supplies, and financial markets.

To reduce the impact of COVID-19 outbreak conditions on businesses, workers, customers, and the public, it is important for all employers to plan now for COVID-19. For employers who have already planned for influenza pandemics, planning for COVID-19 may involve updating plans to address the specific exposure risks, sources of exposure, routes of transmission, and other unique characteristics of SARS-CoV-2 (i.e., compared to pandemic influenza viruses). Employers who have not prepared for pandemic events should prepare themselves and their workers as far in advance as possible of potentially worsening outbreak conditions. Lack of continuity planning can result in a cascade of failures as employers attempt to address challenges of COVID-19 with insufficient resources and workers who might not be adequately trained for jobs they may have to perform under pandemic conditions.

The Occupational Safety and Health Administration (OSHA) developed this COVID-19 planning guidance based on traditional infection prevention and industrial hygiene practices. It focuses on the need for employers to implement engineering, administrative, and work practice controls and personal protective equipment (PPE), as well as considerations for doing so.

This guidance is intended for planning purposes. Employers and workers should use this planning guidance to help identify risk levels in workplace settings and to determine any appropriate control measures to implement. Additional guidance may be needed as COVID-19 outbreak conditions change, including as new information about the virus, its transmission, and impacts, becomes available.

GUIDANCE ON PREPARING WORKPLACES FOR COVID-19

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The U.S. Department of Health and Human Services' Centers for Disease Control and Prevention (CDC) provides the latest information about COVID-19 and the global outbreak: www.cdc.gov/coronavi rus/2019-ncov.

The OSHA COVID-19 webpage offers information specifically for workers and employers: www.osha.gov/covid-19.

This guidance is advisory in nature and informational in content. It is not a standard or a regulation, and it neither creates new legal obligations nor alters existing obligations created by OSHA standards or the Occupational Safety and Health Act (OSH Act). Pursuant to the OSH Act, employers must comply with safety and health standards and regulations issued and enforced either by OSHA or by an OSHA-approved State Plan. In addition, the OSH Act's General Duty Clause, Section 5(a)(1 ), requires employers to provide their employees with a workplace free from recognized hazards likely to cause death or serious physical harm. OSHA-approved State Plans may have standards, regulations and enforcement policies that are different from, but at least as effective as, OSHA's. Check with your State Plan, as applicable, for more information.

About COVID-19

Symptoms of COVID-19

Infection with SARS-CoV-2, the virus that causes COVID-19, can cause illness ranging from mild to severe and, in some cases, can be fatal. Symptoms typically include fever, cough, and shortness of breath. Some people infected with the virus have reported experiencing other non-respiratory symptoms. Other people, referred to as asymptomatic cases, have experienced no symptoms at all.

According to the CDC, symptoms of COVID-19 may appear in as few as 2 days or as long as 14 days after exposure.

OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION

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How COVID-19 Spreads

Although the first human cases of COVID-19 likely resulted from exposure to infected animals, infected people can spread SARS-CoV-2 to other people.

The virus is thought to spread mainly from personto-person, including:

■ Between people who are in close contact with one another (within about 6 feet).

■ Through respiratory

Medium exposure risk jobs include those that require frequent and/or close contact with (i.e., within 6 feet of) other people who may be infected with SARS-CoV-2.

droplets produced when an infected person coughs or sneezes. These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.

It may be possible that a person can get COVID-19 by touching a surface or object that has SARS-CoV-2 on it and then touching their own mouth, nose, or possibly their eyes, but this is not thought to be the primary way the virus spreads.

People are thought to be most contagious when they are most symptomatic (i.e., experiencing fever, cough, and/or shortness of breath). Some spread might be possible before people show symptoms; there have been reports of this type of asymptomatic transmission with this new coronavirus, but this is also not thought to be the main way the virus spreads.

Although the United States has implemented public health measures to limit the spread of the virus, it is likely that some person-to-person transmission will continue to occur.

The CDC website provides the latest information about COVID-19 transmission: www.cdc.gov/coronavirus/2019-ncov/ about/transmission.html.

GUIDANCE ON PREPARING WORKPLACES FOR COVI0-19

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How a COVID-19 Outbreak Could Affect Workplaces Similar to influenza viruses, SARS-CoV-2, the virus that causes COVID-19, has the potential to cause extensive outbreaks. Under conditions associated with widespread person-toperson spread, multiple areas of the United States and other countries may see impacts at the same time. In the absence of a vaccine, an outbreak may also be an extended event. As a result, workplaces may experience:

■ Absenteeism. Workers could be absent because they are sick; are caregivers for sick family members; are caregivers for children if schools or day care centers are closed; have at-risk people at home, such as immunocompromised family members; or are afraid to come to work because of fear of possible exposure.

■ Change in patterns of commerce. Consumer demand for items related to infection prevention (e.g., respirators) is likely to increase significantly, while consumer interest in other goods may decline. Consumers may also change shopping patterns because of a COVID-19 outbreak. Consumers may try to shop at off-peak hours to reduce contact with other people, show increased interest in home delivery services, or prefer other options, such as drivethrough service, to reduce person-to-person contact.

■ Interrupted supply/delivery. Shipments of items from geographic areas severely affected by COVID-19 may be delayed or cancelled with or without notification.

This illustration, created at the Centers for Disease Control and Prevention {CDC), reveals ultrastructural morphology exhibited by the 2019 Novel Coronavirus (2019-nCoV). Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. This virus was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China.

Photo: CDC I Alissa Eckert & Dan Higgins

OCCUPATIONAL SAFETY AND HEAL TH ADMINISTRATION

6


Steps All Employers Can Take to Reduce Workers' Risk of Exposure to SARS-CoV-2 This section describes basic steps that every employer can take to reduce the risk of worker exposure to SARS-CoV-2, the virus that causes COVID-19, in their workplace. Later sections of this guidance-including those focusing on jobs classified as having low, medium, high, and very high exposure risksprovide specific recommendations for employers and workers within specific risk categories.

Develop an Infectious Disease Preparedness and Response Plan

If one does not already exist, develop an infectious disease preparedness and response plan that can help guide protective actions against COVID-19.

Stay abreast of guidance from federal, state, local, tribal, and/or territorial health agencies, and consider how to incorporate those recommendations and resources into workplace-specific plans.

Plans should consider and address the level(s) of risk associated with various worksites and job tasks workers perform at those sites. Such considerations may include:

■ Where, how, and to what sources of SARS-CoV-2 might workers be exposed, including:

o The general public, customers, and coworkers; and

o Sick individuals or those at particularly high risk of infection (e.g., international travelers who have visited locations with widespread sustained (ongoing) COVID-19 transmission, healthcare workers who have had unprotected exposures to people known to have, or suspected of having, COVID-19).

■ Non-occupational risk factors at home and in community settings.


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■ Workers' individual risk factors (e.g., older age; presence of chronic medical conditions, including immunocompromising conditions; pregnancy).

■ Controls necessary to address those risks.

Follow federal and state, local, tribal, and/or territorial (SLTT) recommendations regarding development of contingency plans for situations that may arise as a result of outbreaks, such as:

■ Increased rates of worker absenteeism.

■ The need for social distancing, staggered work shifts, downsizing operations, delivering services remotely, and other exposure-reducing measures.

■ Options for conducting essential operations with a reduced workforce, including cross-training workers across different jobs in order to continue operations or deliver surge services.

■ Interrupted supply chains or delayed deliveries.

Plans should also consider and address the other steps that employers can take to reduce the risk of worker exposure to SARS-CoV-2 in their workplace, described in the sections below.

Prepare to Implement Basic Infection Prevention Measures

For most employers, protecting workers will depend on emphasizing basic infection prevention measures. As appropriate, all employers should implement good hygiene and infection control practices, including:

■ Promote frequent and thorough hand washing, including by providing workers, customers, and worksite visitors with a place to wash their hands. If soap and running water are not immediately available, provide alcohol-based hand rubs containing at least 60% alcohol.

■ Encourage workers to stay home if they are sick.

■ Encourage respiratory etiquette, including covering coughs and sneezes.


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■ Provide customers and the public with tissues and trash receptacles.

■ Employers should explore whether they can establish policies and practices, such as flexible worksites (e.g., telecommuting) and flexible work hours (e.g., staggered shifts), to increase the physical distance among employees and between employees and others if state and local health authorities recommend the use of social distancing strategies.

■ Discourage workers from using other workers' phones, desks, offices, or other work tools and equipment, when possible.

■ Maintain regular housekeeping practices, including routine cleaning and disinfecting of surfaces, equipment, and other elements of the work environment. When choosing cleaning chemicals, employers should consult information on Environmental Protection Agency (EPA)-approved disinfectant labels with claims against emerging viral pathogens. Products with EPA-approved emerging viral pathogens claims are expected to be effective against SARS-CoV-2 based on data for harder to kill viruses. Follow the manufacturer's instructions for use of all cleaning and disinfection products (e.g., concentration, application method and contact time, PPE).

Develop Policies and Procedures for Prompt Identification and Isolation of Sick People, if Appropriate

■ Prompt identification and isolation of potentially infectious individuals is a critical step in protecting workers, customers, visitors, and others at a worksite.

■ Employers should inform and encourage employees to self-monitor for signs and symptoms of COVID-19 if they suspect possible exposure.

■ Employers should develop policies and procedures for employees to report when they are sick or experiencing symptoms of COVID-19.


9


■ Where appropriate, employers should develop policies and procedures for immediately isolating people who have signs and/or symptoms of COVID-19, and train workers to implement them. Move potentially infectious people to a location away from workers, customers, and other visitors. Although most worksites do not have specific isolation rooms, designated areas with closable doors may serve as isolation rooms until potentially sick people can be removed from the worksite.

■ Take steps to limit spread of the respiratory secretions of a person who may have COVID-19. Provide a face mask, if feasible and available, and ask the person to wear it, if tolerated. Note: A face mask (also called a surgical mask, procedure mask, or other similar terms) on a patient or other sick person should not be confused with PPE for a worker; the mask acts to contain potentially infectious respiratory secretions at the source (i.e., the person's nose and mouth).

■ If possible, isolate people suspected of having COVID-19 separately from those with confirmed cases of the virus to prevent further transmission-particularly in worksites where medical screening, triage, or healthcare activities occur, using either permanent (e.g., wall/different room) or temporary barrier (e.g., plastic sheeting).

■ Restrict the number of personnel entering isolation areas.

■ Protect workers in close contact with (i.e., within 6 feet of) a sick person or who have prolonged/repeated contact with such persons by using additional engineering and administrative controls, safe work practices, and PPE. Workers whose activities involve close or prolonged/ repeated contact with sick people are addressed further in later sections covering workplaces classified at medium and very high or high exposure risk.


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Develop, Implement, and Communicate about Workplace Flexibilities and Protections

■ Actively encourage sick employees to stay home.

■ Ensure that sick leave policies are flexible and consistent with public health guidance and that employees are aware of these policies.

■ Talk with companies that provide your business with contract or temporary employees about the importance of sick employees staying home and encourage them to develop non-punitive leave policies.

■ Do not require a healthcare provider's note for employees who are sick with acute respiratory illness to validate their illness or to return to work, as healthcare provider offices and medical facilities may be extremely busy and not able to provide such documentation in a timely way.

■ Maintain flexible policies that permit employees to stay home to care for a sick family member. Employers should be aware that more employees may need to stay at home to care for sick children or other sick family members than is usual.

■ Recognize that workers with ill family members may need to stay home to care for them. See CDC's Interim Guidance for Preventing the Spread of COVID-19 in Homes and Residential Communities: www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-prevent-spread.html.

■ Be aware of workers' concerns about pay, leave, safety, health, and other issues that may arise during infectious disease outbreaks. Provide adequate, usable, and appropriate training, education, and informational material about business-essential job functions and worker health and safety, including proper hygiene practices and the use of any workplace controls (including PPE). Informed workers who feel safe at work are less likely to be unnecessarily absent.


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■ Work with insurance companies (e.g., those providing employee health benefits) and state and local health agencies to provide information to workers and customers about medical care in the event of a COVID-19 outbreak.

Implement Workplace Controls

Occupational safety and health professionals use a framework called the "hierarchy of controls" to select ways of controlling workplace hazards. In other words, the best way to control a hazard is to systematically remove it from the workplace, rather than relying on workers to reduce their exposure. During a COVID-19 outbreak, when it may not be possible to eliminate the hazard, the most effective protection measures are (listed from most effective to least effective): engineering controls, administrative controls, safe work practices (a type of administrative control), and PPE. There are advantages and disadvantages to each type of control measure when considering the ease of implementation, effectiveness, and cost. In most cases, a combination of control measures will be necessary to protect workers from exposure to SARS-CoV-2.

In addition to the types of workplace controls discussed below, CDC guidance for businesses provides employers and workers with recommended SARS-CoV-2 infection prevention strategies to implement in workplaces: www.cdc.gov/coronavirus/2019-ncov/specific-groups/guidance-business-response.html.

Engineering Controls

Engineering controls involve isolating employees from workrelated hazards. In workplaces where they are appropriate, these types of controls reduce exposure to hazards without relying on worker behavior and can be the most cost-effective solution to implement. Engineering controls for SARS-CoV-2 include:

■ Installing high-efficiency air filters.

■ Increasing ventilation rates in the work environment.

■ Installing physical barriers, such as clear plastic sneeze guards.


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■ Installing a drive-through window for customer service.

■ Specialized negative pressure ventilation in some settings, such as for aerosol generating procedures (e.g., airborne infection isolation rooms in healthcare settings and specialized autopsy suites in mortuary settings).

Administrative Controls

Administrative controls require action by the worker or employer. Typically, administrative controls are changes in work policy or procedures to reduce or minimize exposure to a hazard. Examples of administrative controls for SARS-CoV-2 include:

■ Encouraging sick workers to stay at home.

■ Minimizing contact among workers, clients, and customers by replacing face-to-face meetings with virtual communications and implementing telework if feasible.

■ Establishing alternating days or extra shifts that reduce the total number of employees in a facility at a given time, allowing them to maintain distance from one another while maintaining a full onsite work week.

■ Discontinuing nonessential travel to locations with ongoing COVID-19 outbreaks. Regularly check CDC travel warning levels at: www.cdc.gov/coronavirus/2019-ncov/travelers.

■ Developing emergency communications plans, including a forum for answering workers' concerns and internet-based communications, if feasible.

■ Providing workers with up-to-date education and training on COVID-19 risk factors and protective behaviors (e.g., cough etiquette and care of PPE).

■ Training workers who need to use protecting clothing and equipment how to put it on, use/wear it, and take it off correctly, including in the context of their current and potential duties. Training material should be easy to understand and available in the appropriate language and literacy level for all workers.


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Safe Work Practices

Safe work practices are types of administrative controls that include procedures for safe and proper work used to reduce the duration, frequency, or intensity of exposure to a hazard. Examples of safe work practices for SARS-CoV-2 include:

■ Providing resources and a work environment that promotes personal hygiene. For example, provide tissues, no-touch trash cans, hand soap, alcohol-based hand rubs containing at least 60 percent alcohol, disinfectants, and disposable towels for workers to clean their work surfaces.

■ Requiring regular hand washing or using of alcohol-based hand rubs. Workers should always wash hands when they are visibly soiled and after removing any PPE.

■ Post handwashing signs in restrooms.

Personal Protective Equipment (PPE)

While engineering and administrative controls are considered more effective in minimizing exposure to SARS-CoV-2, PPE may also be needed to prevent certain exposures. While correctly using PPE can help prevent some exposures, it should not take the place of other prevention strategies.

Examples of PPE include: gloves, goggles, face shields, face masks, and respiratory protection, when appropriate. During an outbreak of an infectious disease, such as COVID-19, recommendations for PPE specific to occupations or job tasks may change depending on geographic location, updated risk assessments for workers, and information on PPE effectiveness in preventing the spread of COVID-19. Employers should check the OSHA and CDC websites regularly for updates about recommended PPE.

All types of PPE must be:

■ Selected based upon the hazard to the worker.

■ Properly fitted and periodically refitted, as applicable (e.g., respirators).


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■ Consistently and properly worn when required.

■ Regularly inspected, maintained, and replaced, as necessary.

■ Properly removed, cleaned, and stored or disposed of, as applicable, to avoid contamination of self, others, or the environment.

Employers are obligated to provide their workers with PPE needed to keep them safe while performing their jobs. The types of PPE required during a COVID-19 outbreak will be based on the risk of being infected with SARS-CoV-2 while working and job tasks that may lead to exposure.

Workers, including those who work within 6 feet of patients known to be, or suspected of being, infected with SARS-CoV-2 and those performing aerosol-generating procedures, need to use respirators:

■ National Institute for Occupational Safety and Health (NIOSH)-approved, N95 filtering facepiece respirators or better must be used in the context of a comprehensive, written respiratory protection program that includes fit-testing, training, and medical exams. See OSHA's Respiratory Protection standard, 29 CFR 1910.134 at www.osha.gov/laws-regs/regulations/ standardnumber/1910/1910.134.

■ When disposable N95 filtering facepiece respirators are not available, consider using other respirators that provide greater protection and improve worker comfort. Other types of acceptable respirators include: a R/P95, N/R/P99, or N/R/P100 filtering facepiece respirator; an air-purifying elastomeric (e.g., half-face or full-face) respirator with appropriate filters or cartridges; powered air purifying respirator (PAPR) with high-efficiency particulate arrestance (HEPA) filter; or supplied air respirator (SAR). See CDC/ NIOSH guidance for optimizing respirator supplies at: www.cdc.gov/coronavirus/2019-ncov/hcp/respirators-strategy.


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■ Consider using PAPRs or SARs, which are more protective than filtering facepiece respirators, for any work operations or procedures likely to generate aerosols (e.g., cough induction procedures, some dental procedures, invasive specimen collection, blowing out pipettes, shaking or vortexing tubes, filling a syringe, centrifugation).

■ Use a surgical N95 respirator when both respiratory protection and resistance to blood and body fluids is needed.

■ Face shields may also be worn on top of a respirator to prevent bulk contamination of the respirator. Certain respirator designs with forward protrusions (duckbill style) may be difficult to properly wear under a face shield. Ensure that the face shield does not prevent airflow through the respirator.

■ Consider factors such as function, fit, ability to decontaminate, disposal, and cost. OSHA's Respiratory Protection eTool provides basic information on respirators such as medical requirements, maintenance and care, fit testing, written respiratory protection programs, and voluntary use of respirators, which employers may also find beneficial in training workers at: www.osha.gov/SLTC/ etools/respiratory. Also see NIOSH respirator guidance at: www.cdc.gov/niosh/topics/respirators.

■ Respirator training should address selection, use (including donning and doffing), proper disposal or disinfection, inspection for damage, maintenance, and the limitations of respiratory protection equipment. Learn more at: www. osha.gov/SLTC/respiratoryprotection.

■ The appropriate form of respirator will depend on the type of exposure and on the transmission pattern of COVID-19. See the NIOSH "Respirator Selection Logic" at: www.cdc.gov/niosh/docs/2005-100/default.html or the OSHA "Respiratory Protection eTool" at www.osha.gov/ SLTC/etools/respiratory.


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Follow Existing OSHA Standards

Existing OSHA standards may apply to protecting workers from exposure to and infection with SARS-CoV-2.

While there is no specific OSHA standard covering SARSCoV-2 exposure, some OSHA requirements may apply to preventing occupational exposure to SARS-CoV-2. Among the most relevant are:

■ OSHA's Personal Protective Equipment (PPE) standards (in general industry, 29 CFR 1910 Subpart I), which require using gloves, eye and face protection, and respiratory protection. See: www.osha.gov/laws-regs/regulations/ standardnumber/1910#191 0_Su bpart_l.

o When respirators are necessary to protect workers or where employers require respirator use, employers must implement a comprehensive respiratory protection program in accordance with the Respiratory Protection standard (29 CFR 1910.134). See: www.osha.gov/lawsregs/regu lations/standardnum ber/1910/1910.134.

■ The General Duty Clause, Section 5(a)(1) of the Occupational Safety and Health (OSH) Act of 1970, 29 USC 654(a)(1 ), which requires employers to furnish to each worker "employment and a place of employment, which are free from recognized hazards that are causing or are likely to cause death or serious physical harm." See: www.osha.gov/laws-regs/oshact/completeoshact.

OSHA's Bloodborne Pathogens standard (29 CFR 1910.1030) applies to occupational exposure to human blood and other potentially infectious materials that typically do not include respiratory secretions that may transmit SARS-CoV-2. However, the provisions of the standard offer a framework that may help control some sources of the virus, including exposures to body fluids (e.g., respiratory secretions) not covered by the standard. See: www.osha.gov/laws-regs/ regulations/standardnumber/1910/1910.1030.


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The OSHA COVID-19 webpage provides additional information about OSHA standards and requirements, including requirements in states that operate their own OSHA-approved State Plans, recordkeeping requirements and injury/illness recording criteria, and applications of standards related to sanitation and communication of risks related to hazardous chemicals that may be in common sanitizers and sterilizers. See: www.osha.gov/SLTC/covid-19/standards.html.

Classifying Worker Exposure to SARS-CoV-2 Worker risk of occupational exposure to SARS-CoV-2, the virus that causes COVID-19, during an outbreak may vary from very high to high, medium, or lower (caution) risk. The level of risk depends in part on the industry type, need for contact within 6 feet of people known to be, or suspected of being, infected with SARS-CoV-2, or requirement for repeated or extended contact with persons known to be, or suspected of being, infected with SARS-CoV-2. To help employers determine appropriate precautions, OSHA has divided job tasks into four risk exposure levels: very high, high, medium, and lower risk. The Occupational Risk Pyramid shows the four exposure risk levels in the shape of a pyramid to represent probable distribution of risk. Most American workers will likely fall in the lower exposure risk (caution) or medium exposure risk levels.

Occupational Risk Pyramid for COVID-19


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Very High Exposure Risk

Very high exposure risk jobs are those with high potential for exposure to known or suspected sources of COVID-19 during specific medical, postmortem, or laboratory procedures. Workers in this category include:

■ Healthcare workers (e.g., doctors, nurses, dentists, paramedics, emergency medical technicians) performing aerosol-generating procedures (e.g., intubation, cough induction procedures, bronchoscopies, some dental procedures and exams, or invasive specimen collection) on known or suspected COVID-19 patients.

■ Healthcare or laboratory personnel collecting or handling specimens from known or suspected COVID-19 patients (e.g., manipulating cultures from known or suspected COVID-19 patients).

■ Morgue workers performing autopsies, which generally involve aerosol-generating procedures, on the bodies of people who are known to have, or suspected of having, COVID-19 at the time of their death.

High Exposure Risk

High exposure risk jobs are those with high potential for exposure to known or suspected sources of COVID-19. Workers in this category include:

■ Healthcare delivery and support staff (e.g., doctors, nurses, and other hospital staff who must enter patients' rooms) exposed to known or suspected COVID-19 patients. (Note: when such workers perform aerosol-generating procedures, their exposure risk level becomes very high.)

■ Medical transport workers (e.g., ambulance vehicle operators) moving known or suspected COVID-19 patients in enclosed vehicles.

■ Mortuary workers involved in preparing (e.g., for burial or cremation) the bodies of people who are known to have, or suspected of having, COVID-19 at the time of their death.

GUIDANCE ON PREPARING WORKPLACES FOR COVID-19 , 9


Medium Exposure Risk

Medium exposure risk jobs include those that require frequent and/or close contact with (i.e., within 6 feet of) people who may be infected with SARS-CoV-2, but who are not known or suspected COVID-19 patients. In areas without ongoing community transmission, workers in this risk group may have frequent contact with travelers who may return from international locations with widespread COVID-19 transmission. In areas where there is ongoing community transmission, workers in this category may have contact with the general public (e.g., schools, high-population-density work environments, some high-volume retail settings).

Lower Exposure Risk (Caution)

Lower exposure risk (caution) jobs are those that do not require contact with people known to be, or suspected of being, infected with SARS-CoV-2 nor frequent close contact with (i.e., within 6 feet of) the general public. Workers in this category have minimal occupational contact with the public and other coworkers.

Jobs Classified at Lower Exposure Risk (Caution): What to Do to Protect Workers For workers who do not have frequent contact with the general public, employers should follow the guidance for "Steps All Employers Can Take to Reduce Workers' Risk of Exposure to SARS-CoV-2," on page 7 of this booklet and implement control measures described in this section.


Additional engineering controls are not recommended for workers in the lower exposure risk group. Employers should ensure that engineering controls, if any, used to protect workers from other job hazards continue to function as intended.


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■ Monitor public health communications about COVID-19 recommendations and ensure that workers have access to that information. Frequently check the CDC COVID-19 website: www.cdc.gov/coronavirus/2019-ncov.

■ Collaborate with workers to designate effective means of communicating important COVID-19 information.

Personal Protective Equipment

Additional PPE is not recommended for workers in the lower exposure risk group. Workers should continue to use the PPE, if any, that they would ordinarily use for other job tasks.

Jobs Classified at Medium Exposure Risk: What to Do to Protect Workers In workplaces where workers have medium exposure risk, employers should follow the guidance for "Steps All Employers Can Take to Reduce Workers' Risk of Exposure to SARS-CoV-2," on page 7 of this booklet and implement control measures described in this section.


■ Install physical barriers, such as clear plastic sneeze guards, where feasible.


■ Consider offering face masks to ill employees and customers to contain respiratory secretions until they are able leave the workplace (i.e., for medical evaluation/care or to return home). In the event of a shortage of masks, a reusable face shield that can be decontaminated may be an acceptable method of protecting against droplet transmission. See CDC/ NIOSH guidance for optimizing respirator supplies, which discusses the use of surgical masks, at: www.cdc.gov/ coronavirus/2019-ncov/hcp/respirators-strategy.


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■ Keep customers informed about symptoms of COVID-19 and ask sick customers to minimize contact with workers until healthy again, such as by posting signs about COVID-19 in stores where sick customers may visit (e.g., pharmacies) or including COVID-19 information in automated messages sent when prescriptions are ready for pick up.

■ Where appropriate, limit customers' and the public's access to the worksite, or restrict access to only certain workplace areas.

■ Consider strategies to minimize face-to-face contact (e.g., drivethrough windows, phone-based communication, telework).

■ Communicate the availability of medical screening or other worker health resources (e.g., on-site nurse; telemedicine services).


When selecting PPE, consider factors such as function, fit, decontamination ability, disposal, and cost. Sometimes, when PPE will have to be used repeatedly for a long period of time, a more expensive and durable type of PPE may be less expensive overall than disposable PPE. Each employer should select the combination of PPE that protects workers specific to their workplace.

Workers with medium exposure risk may need to wear some combination of gloves, a gown, a face mask, and/or a face shield or goggles. PPE ensembles for workers in the medium exposure risk category will vary by work task, the results of the employer's hazard assessment, and the types of exposures workers have on the job.

High exposure risk jobs are those with high potential for exposure to known or suspected sources of COVID-19.

Very high exposure risk jobs are those with high potential for exposure to known or suspected sources of COVID-19 during specific medical, postmortem, or laboratory procedures that involve aerosol generation or specimen collection/ handling.


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In rare situations that would require workers in this risk category to use respirators, see the PPE section beginning on page 14 of this booklet, which provides more details about respirators. For the most up-to-date information, visit OSHA's COVID-19 webpage: www.osha.gov/covid-19.

Jobs Classified at High or Very High Exposure Risk: What to Do to Protect Workers In workplaces where workers have high or very high exposure risk, employers should follow the guidance for "Steps All Employers Can Take to Reduce Workers' Risk of Exposure to SARS-CoV-2," on page 7 of this booklet and implement control measures described in this section.


■ Ensure appropriate air-handling systems are installed and maintained in healthcare facilities. See "Guidelines for Environmental Infection Control in Healthcare Facilities" for more recommendations on air handling systems at: www. cdc.gov/mmwr/preview/mmwrhtml/rr5210a1 .htm.

■ CDC recommends that patients with known or suspected COVID-19 (i.e., person under investigation) should be placed in an airborne infection isolation room (AIIR), if available.

■ Use isolation rooms when available for performing aerosol-generating procedures on patients with known or suspected COVID-19. For postmortem activities, use autopsy suites or other similar isolation facilities when performing aerosol-generating procedures on the bodies of people who are known to have, or suspected of having, COVID-19 at the time of their death. See the CDC postmortem guidance at: www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-postmortem-specimens.html. OSHA also provides guidance for postmortem activities on its COVID-19 webpage: www.osha.gov/covid-19.


2 3


■ Use special precautions associated with Biosafety Level 3 when handling specimens from known or suspected COVID-19 patients. For more information about biosafety levels, consult the U.S. Department of Health and Human Services (HHS) "Biosafety in Microbiological and Biomedical Laboratories" at www.cdc.gov/biosafety/ publications/bmbl5.


If working in a healthcare facility, follow existing guidelines and facility standards of practice for identifying and isolating infected individuals and for protecting workers.

■ Develop and implement policies that reduce exposure, such as cohorting (i.e., grouping) COVID-19 patients when single rooms are not available.

■ Post signs requesting patients and family members to immediately report symptoms of respiratory illness on arrival at the healthcare facility and use disposable face masks.

■ Consider offering enhanced medical monitoring of workers during COVID-19 outbreaks.

■ Provide all workers with job-specific education and training on preventing transmission of COVID-19, including initial and routine/refresher training.

■ Ensure that psychological and behavioral support is available to address employee stress.

Safe Work Practices

■ Provide emergency responders and other essential personnel who may be exposed while working away from fixed facilities with alcohol-based hand rubs containing at least 60% alcohol for decontamination in the field.


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Most workers at high or very high exposure risk likely need to wear gloves, a gown, a face shield or goggles, and either a face mask or a respirator, depending on their job tasks and exposure risks.

Those who work closely with (either in contact with or within 6 feet of) patients known to be, or suspected of being, infected with SARS-CoV-2, the virus that causes COVID-19, should wear respirators. In these instances, see the PPE section beginning on page 14 of this booklet, which provides more details about respirators. For the most up-to-date information, also visit OSHA's COVID-19 webpage: www.osha.gov/covid-19.

PPE ensembles may vary, especially for workers in laboratories or morgue/mortuary facilities who may need additional protection against blood, body fluids, chemicals, and other materials to which they may be exposed. Additional PPE may include medical/surgical gowns, fluid-resistant coveralls, aprons, or other disposable or reusable protective clothing. Gowns should be large enough to cover the areas requiring protection. OSHA may also provide updated guidance for PPE use on its website: www.osha.gov/covid-19.

NOTE: Workers who dispose of PPE and other infectious waste must also be trained and provided with appropriate PPE.

The CDC webpage "Healthcare-associated Infections" (www.cdc.gov/hai) provides additional information on infection control in healthcare facilities.

Workers Living Abroad or Travelling Internationally Employers with workers living abroad or traveling on international business should consult the "Business Travelers" section of the OSHA COVID-19 webpage (www.osha.gov/covid-19), which also provides links to the latest:


2 5


■ CDC travel warnings: www.cdc.gov/ coronavirus/2019-ncov/travelers

■ U.S. Department of State (DOS) travel advisories: travel.state.gov

Employers should communicate to workers that the DOS cannot provide Americans traveling or living abroad with medications or supplies, even in the event of a COVID-19 outbreak.

As COVID-19 outbreak conditions change, travel into or out of a country may not be possible, safe, or medically advisable. It is also likely that governments will respond to a COVID-19 outbreak by imposing public health measures that restrict domestic and international movement, further limiting the U.S. government's ability to assist Americans in these countries. It is important that employers and workers plan appropriately, as it is possible that these measures will be implemented very quickly in the event of worsening outbreak conditions in certain areas.

More information on COVID-19 planning for workers living and traveling abroad can be found at: www.cdc.gov/travel.

For More Information Federal, state, and local government agencies are the best source of information in the event of an infectious disease outbreak, such as COVID-19. Staying informed about the latest developments and recommendations is critical, since specific guidance may change based upon evolving outbreak situations.

Below are several recommended websites to access the most current and accurate information:

■ Occupational Safety and Health Administration website: www.osha.gov

■ Centers for Disease Control and Prevention website: www.cdc.gov

■ National Institute for Occupational Safety and Health website: www.cdc.gov/niosh


2 6


OSHA Assistance, Services, and Programs OSHA has a great deal of information to assist employers in complying with their responsibilities under OSHA law. Several OSHA programs and services can help employers identify and correct job hazards, as well as improve their safety and health program.

Establishing a Safety and Health Program

Safety and health programs are systems that can substantially reduce the number and severity of workplace injuries and illnesses, while reducing costs to employers.

Visit www.osha.gov/safetymanagement for more information.

Compliance Assistance Specialists

OSHA compliance assistance specialists can provide information to employers and workers about OSHA standards, short educational programs on specific hazards or OSHA rights and responsibilities, and information on additional compliance assistance resources.

Visit www.osha.gov/complianceassistance/cas or call 1-800-321-OSHA (6742) to contact your local OSHA office.

No-Cost On-Site Safety and Health Consultation Services for Small Business

OSHA's On-Site Consultation Program offers no-cost and confidential advice to small and medium-sized businesses in all states, with priority given to high-hazard worksites. On-Site consultation services are separate from enforcement and do not result in penalties or citations.

For more information or to find the local On-Site Consultation office in your state, visit www.osha.gov/consultation, or call 1-800-321-OSHA (6742).


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Under the consultation program, certain exemplary employers may request participation in OSHA's Safety and Health Achievement Recognition Program (SHARP). Worksites that receive SHARP recognition are exempt from programmed inspections during the period that the SHARP certification is valid.

Cooperative Programs

OSHA offers cooperative programs under which businesses, labor groups and other organizations can work cooperatively with OSHA. To find out more about any of the following programs, visit www.osha.gov/cooperativeprograms.

Strategic Partnerships and Alliances

The OSHA Strategic Partnerships (OSP) provide the opportunity for OSHA to partner with employers, workers, professional or trade associations, labor organizations, and/or other interested stakeholders. Through the Alliance Program, OSHA works with groups to develop compliance assistance tools and resources to share with workers and employers, and educate workers and employers about their rights and responsibilities.

Voluntary Protection Programs {VPP}

The VPP recognize employers and workers in the private sector and federal agencies who have implemented effective safety and health programs and maintain injury and illness rates below the national average for their respective industries.

Occupational Safety and Health Training

OSHA partners with 26 OSHA Training Institute Education Centers at 37 locations throughout the United States to deliver courses on OSHA standards and occupational safety and health topics to thousands of students a year. For more information on training courses, visit www.osha.gov/otiec.


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OSHA Educational Materials

OSHA has many types of educational materials to assist employers and workers in finding and preventing workplace hazards.

All OSHA publications are free at www.osha.gov/publications and www.osha.gov/ebooks. You can also call 1-800-321-OSHA (6742) to order publications.

Employers and safety and health professionals can sign-up for QuickTakes, OSHA's free, twice-monthly online newsletter with the latest news about OSHA initiatives and products to assist in finding and preventing workplace hazards. To sign up, visit www.osha.gov/quicktakes.

OSHA Regional Offices Region 1 Boston Regional Office (CT*, ME*, MA, NH, RI, VT*) JFK Federal Building 25 New Sudbury Street, Room E340 Boston, MA 02203 (617) 565-9860 (617) 565-9827 Fax

Region 2 New York Regional Office (NJ*, NY*, PR*, VI*) Federal Building 201 Varick Street, Room 670 New York, NY 10014 (212) 337-2378 (212) 337-2371 Fax

Region 3 Philadelphia Regional Office (DE, DC, MD*, PA, VA*, WV) The Curtis Center 170 S. Independence Mall West, Suite 740 West Philadelphia, PA 19106-3309 (215) 861-4900 (215) 861-4904 Fax


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Region 4 Atlanta Regional Office (AL, FL, GA, KY*, MS, NC*, SC*, TN*) Sam Nunn Atlanta Federal Center 61 Forsyth Street, SW, Room 6T50 Atlanta, GA 30303 (678) 237-0400 (678) 237-0447 Fax

Region 5 Chicago Regional Office {IL*, IN*, Ml*, MN*, OH, WI) John C. Kluczynski Federal Building 230 South Dearborn Street, Room 3244 Chicago, IL 60604 (312) 353-2220 (312) 353-7774 Fax

Region 6 Dallas Regional Office (AR, LA, NM*, OK, TX) A. Maceo Smith Federal Building 525 Griffin Street, Room 602 Dallas, TX 75202 (972) 850-4145 (972) 850-4149 Fax

Region 7 Kansas City Regional Office {IA*, KS, MO, NE) Two Pershing Square Building 2300 Main Street, Suite 1010 Kansas City, MO 64108-2416 (816) 283-8745 (816) 283-0547 Fax

Region 8 Denver Regional Office (CO, MT, ND, SD, UT*, WY*) Cesar Chavez Memorial Building 1244 Speer Boulevard, Suite 551 Denver, CO 80204 (720) 264-6550 (720) 264-6585 Fax


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Region 9 San Francisco Regional Office (AZ*, CA*, HI*, NV*, and American Samoa, Guam and the Northern Mariana Islands) San Francisco Federal Building 90 7th Street, Suite 2650 San Francisco, CA 94103 (415) 625-2547 (415) 625-2534 Fax

Region 10 Seattle Regional Office (AK*, ID, OR*, WA*) Fifth & Yesler Tower 300 Fifth Avenue, Suite 1280 Seattle, WA 98104 (206) 757-6700 (206) 757-6705 Fax

*These states and territories operate their own OSHA-approved job safety and health plans and cover state and local government employees as well as private sector employees. The Connecticut, Illinois, Maine, New Jersey, New York and Virgin Islands programs cover public employees only. (Private sector workers in these states are covered by Federal OSHA). States with approved programs must have standards that are identical to, or at least as effective as, the Federal OSHA standards.

Note: To get contact information for OSHA area offices, OSHA-approved state plans and OSHA consultation projects, please visit us online at www.osha.gov or call us at 1-800-321-OSHA (6742).


3 1


How to Contact OSHA Under the Occupational Safety and Health Act of 1970,

employers are responsible for providing safe and healthful workplaces for their employees. OSHA's role is to help ensure these conditions for America's working men and women by

setting and enforcing standards, and providing training, education and assistance. For more information, visit www.osha.gov or call

OSHA at 1-800-321-OSHA (6742), TTY 1-877-889-5627.

For assistance, contact us. We are OSHA. We can help.

O)SfIX www.osha.gov


32


APPENDIX TO JAMES CASCIANO DE CLARA TION-220

Rational use of face masks in the COVID-19 pandemic Since the outbreak of severe acute respiratory syndrome coronavirus 2

(SARS-CoV-2), the virus that caused coronavirus disease 2019 (COVID-19),

the use of face masks has become ubiquitous in China and other Asian

countries such as South Korea and Japan. Some provinces and

municipalities in China have enforced compulsory face mask policies in

public areas; however, China's national guideline has adopted a risk-based

approach in offering recommendations for using face masks among health

care workers and the general public. We compared face mask use

recommendations by different health authorities (panel ). Despite the

consistency in the recommendation that symptomatic individuals and those

in health-care settings should use face masks, discrepancies were

observed in the general public and community settings. 1, 2, 3, 4 , 5, 6, 7, 8 For

example, the US Surgeon General advised against buying masks for use by

healthy people. One important reason to discourage widespread use of face

masks is to preserve limited supplies for professional use in health-care

settings. Universal face mask use in the community has also been

discouraged with the argument that face masks provide no effective

protection against coronavirus infection.

Panel

Recommendations on face mask use in community settings

WH0 1

• If you are healthy, you only need to wear a mask if you are taking care of a

person with suspected SARS-CoV-2 infection.

China 2


• People at moderate risk* of infection: surgical or disposable mask for

medical use.

• People at low riskt of infection: disposable mask for medical use.

• People at very low risk* of infection: do not have to wear a mask or can

wear non-medical mask (such as cloth mask).

Hong Kong 3

• Surgical masks can prevent transmission of respiratory viruses from

people who are ill. It is essential for people who are symptomatic (even if

they have mild symptoms) to wear a surgical mask.

• Wear a surgical mask when taking public transport or staying in crowded

places. It is important to wear a mask properly and practice good hand

hygiene before wearing and after removing a mask.

Singapore 4

• Wear a mask if you have respiratory symptoms, such as a cough or runny

nose.

Japan 5

• The effectiveness of wearing a face mask to protect yourself from

contracting viruses is thought to be limited. If you wear a face mask in

confined, badly ventilated spaces, it might help avoid catching droplets

emitted from others but if you are in an open-air environment, the use of

face mask is not very efficient.

USA 6

• Centers for Disease Control and Prevention does not recommend that

people who are well wear a face mask (including respirators) to protect

themselves from respiratory diseases, including COVID-19.

• US Surgeon General urged people on Twitter to stop buying face masks.


UK7

• Face masks play a very important role in places such as hospitals, but

there is very little evidence of widespread benefit for members of the

public.

Germany8

• There is not enough evidence to prove that wearing a surgical mask

significantly reduces a healthy person's risk of becoming infected while

wearing it. According to WHO, wearing a mask in situations where it is not

recommended to do so can create a false sense of security because it

might lead to neglecting fundamental hygiene measures, such as proper

hand hygiene.

However, there is an essential distinction between absence of evidence and

evidence of absence. Evidence that face masks can provide effective

protection against respiratory infections in the community is scarce, as

acknowledged in recommendations from the UK and Germany.7, 8 However,

face masks are widely used by medical workers as part of droplet

precautions when caring for patients with respiratory infections. It would be

reasonable to suggest vulnerable individuals avoid crowded areas and use

surgical face masks rationally when exposed to high-risk areas. As evidence

suggests COVID-19 could be transmitted before symptom onset,

community transmission might be reduced if everyone, including people

who have been infected but are asymptomatic and contagious, wear face

masks.

Recommendations on face masks vary across countries and we have seen

that the use of masks increases substantially once local epidemics begin,

including the use of N95 respirators (without any other protective

equipment) in community settings. This increase in use of face masks by

the general public exacerbates the global supply shortage of face masks,

with prices soaring,9 and risks supply constraints to frontline health-care


professionals. As a response, a few countries (eg, Germany and South

Korea) banned exportation of face masks to prioritise local demand. 10 WHO

called for a 40% increase in the production of protective equipment,

including face masks.9 Meanwhile, health authorities should optimise face

mask distribution to prioritise the needs of frontline health-care workers and

the most vulnerable populations in communities who are more susceptible

to infection and mortality if infected, including older adults (particularly

those older than 65 years) and people with underlying health conditions.

People in some regions (eg, Thailand, China, and Japan) opted for

makeshift alternatives or repeated usage of disposable surgical masks.

Notably, improper use of face masks, such as not changing disposable

masks, could jeopardise the protective effect and even increase the risk of

infection.

Consideration should also be given to variations in societal and cultural

paradigms of mask usage. The contrast between face mask use as hygienic

practice (ie, in many Asian countries) or as something only people who are

unwell do (ie, in European and North American countries) has induced

stigmatisation and racial aggravations, for which further public education is

needed. One advantage of universal use of face masks is that it prevents

discrimination of individuals who wear masks when unwell because

everybody is wearing a mask.

It is time for governments and public health agencies to make rational

recommendations on appropriate face mask use to complement their

recommendations on other preventive measures, such as hand hygiene.

WHO currently recommends that people should wear face masks if they

have respiratory symptoms or if they are caring for somebody with

symptoms. Perhaps it would also be rational to recommend that people in

quarantine wear face masks if they need to leave home for any reason, to

prevent potential asymptomatic or presymptomatic transmission. In

addition, vulnerable populations, such as older adults and those with


underlying medical conditions, should wear face masks if available.

Universal use of face masks could be considered if supplies permit. In

parallel, urgent research on the duration of protection of face masks, the

measures to prolong life of disposable masks, and the invention on reusable

masks should be encouraged. Taiwan had the foresight to create a large

stockpile of face masks; other countries or regions might now consider this

as part of future pandemic plans.

Cogyright © 2020 Sputnik/Science Photo Library

Since January 2020 Elsevier has created a COVID-19 resource centre with

free information in English and Mandarin on the novel coronavirus COVID-

19. The COVID-19 resource centre is hosted on Elsevier Connect, the

company's public news and information website. Elsevier hereby grants

permission to make all its COVID-19-related research that is available on the

COVID-19 resource centre - including this research content - immediately

available in PubMed Central and other publicly funded repositories, such as

the WHO COVID database with rights for unrestricted research re-use and

analyses in any form or by any means with acknowledgement of the original

source. These permissions are granted for free by Elsevier for as long as the APPENDIX TO JAMES CASCIANO DE CLARA TION-225

COVID-19 resource centre remains active.

Editorial note: the Lancet Group takes a neutral position with respect to

territorial claims in published maps and institutional affiliations.


Face masks are 1NOT necessary• and could even harm the fight against coronavirus, say Holland 1s top scientists Thomas Burrows 2 Aug 2020,

SCIENTISTS in the Netherlands have said face masks in public places

are "not necessary" and might even have a "negative impact".

The Dutch have not made it compulsory to wear face coverings in public -

despite a rise in coronavirus cases.

4

The Netherlands's top scientists still believe there is no medical evidence to support wearing face

masksCredit: AFP


The nation's top scientists have concluded there is no firm evidence to

make people wear masks.

This is despite the fact the Netherlands has seen an alarming spike in

coronavirus cases since restrictions were eased.

Over the past week, almost 1,400 new coronavirus cases were reported, or

342 more than the week before.

However, the country's top scientists still believe there is no medical

evidence to support wearing face masks - even though 120 countries

across the globe have made them mandatory in public.

4

There has been a spike in coronavirus cases in Netherlands in the last week, as seen across EuropeCredit:

AFP


4

Boris Johnson announced that from August 8, Brits will have to wear coverings in cinemas, museums and

galleries Credit: Crown Copyright

Dutch Medical Care Minister Tamara van Ark said: "From a medical point of

view, there is no evidence of a medical effect of wearing face masks, so we

decided not to impose a national obligation."

Coen Berends, spokesman for the National Institute for Public Health and

the Environment, added: "Face masks in public places are not necessary,

based on all the current evidence,

"There is no benefit and there may even be negative impact."

Holland's position is based on assessments by the Outbreak Management

Team, a group of experts advising the government.

It first ruled against masks in May and has re-evaluated the evidence

several times, including again last week.


However Dutch residents must still wear face coverings on public transport.

'EVIDENCE IS CONTRADICTORY'

Christian Hoebe, a professor of infectious diseases in Maastricht and

member of the advisory team, said: 11Face masks should not be seen as a

magic bullet that halts the spread.

"The evidence for them is contradictory. In general, we think you must be

careful with face masks because they can give a false sense of security.

People think they're immune from disease or stop social distancing. That is

very negative."

It puts the Netherlands at odds with most other countries in the world.

Even US President Donald Trump has since done an about-turn and urged

Americans to wear face masks, saying it was "patriotic" to do so (after

previously mocking Joe Biden for wearing one).

In the England, face masks have been compulsory on public transport from

June 15 and in shops and supermarkets from July 24.

From August 8 they: will also be reguired in glaces y:ou come into "contact

with geogle Y.OU do not normallY. meet, such as museums,_galleries, cinemas

and glaces of worshi~.

GRIM TOLL

Covid deaths jump by 1,248 in 24 hours, passing 1 k for third day running


MUTANT SPREAD

Fears Brazilian Covid strain could re-infect those who have fought off virus

TAX BREAK 1SCRAP 1

Rishi Sunak 'refuses to extend stamp duty holiday beyond end of March'

lll'l

MASK ROW

Banker fired after defending 'teen racially abused & kicked in face in bus attack'

SNOWED IN

Snow and ice warning issued for UK this weekend as wintery weather causes chaos


CODE RED

Major incident in Yorkshire after heavy snow leaves ambulance service overwhelmed

The science around wearing a face covering has changed during the

pandemic.

At the outset, the World Health Organisation said healthy people did not

need to wear a mask, unless they were caring for someone who was sick.

Then in April, the WHO said masks could prove useful.

Shortly thereafter, the European Centre for Disease Prevention and Control

issued new recommendations, signalling increased support for masks.

Finally, in June, the WHO said they should be worn in public places where

social distancing is not possible to help stop the spread of coronavirus.

Boris Johnson tells Brits to wear face masks, with police given more powers to enforce as rules extended amid fears of coronavirus second wave


4

US President Donald Trump has done an about-turn and urged Americans to wear face masks, saying it was

"patriotic"Credit: Reuters


Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness Abstract

Background. Despite the availability of published data on 4 pandemics that

have occurred over the past 120 years, there is little modern information on

the causes of death associated with influenza pandemics.

Methods. We examined relevant information from the most recent influenza

pandemic that occurred during the era prior to the use of antibiotics, the

1918-1919 "Spanish flu"; pandemic. We examined lung tissue sections

obtained during 58 autopsies and reviewed pathologic and bacteriologic

data from 109 published autopsy series that described 8398 individual

autopsy investigations.

Results. The postmortem samples we examined from people who died of

influenza during 1918-1919 uniformly exhibited severe changes indicative of

bacterial pneumonia. Bacteriologic and histopathologic results from

published autopsy series clearly and consistently implicated secondary

bacterial pneumonia caused by common upper respiratory-tract bacteria in

most influenza fatalities.

Conclusions. The majority of deaths in the 1918-1919 influenza pandemic

likely resulted directly from secondary bacterial pneumonia caused by

common upper respiratory-tract bacteria. Less substantial data from the

subsequent 1957 and 1968 pandemics are consistent with these findings. If

severe pandemic influenza is largely a problem of viral-bacterial

copathogenesis, pandemic planning needs to go beyond addressing the


,:'.r•,-., '. \· 11 C-i 1

l --. d

'' I

severe pandemic [2].

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--- ' • ~--' ·-✓ • ..... ,' •

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. 1 r . n 1,... "Ir" ! ' • , • i • l . i ' • ' 111 . d'I o- 8 i ::>, ano nave rev,evveo ep1ae1:--11c;:c>;;:c1 patno1og:ci ar:c

r-nicrobiologic data frorn published repor·ts for 3398 oost1·no1·i:2;Y1

exarninations bearing en this question. VVehave also revievved r-e,b .. d:TL

liJanden1ic influenza virus. investic2tors have !Jec1iun to eJ<2;T·ine vJh\1 it ,i,,,1;s

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conclude here that influenza A virus infection in c:onjunction \'/j-: c!c:C[er1a! ·111-:=,, P,. r', ·t ·1· 0 ,·1 1, (=·-ri. ~l-:""'i 1··1~10 C: t. u~-. .-1. ,l'. 1~1' 0 r! .----. ~, i- '1 ·1 ·~ 01 LIi" ·, 1-, ,-., t 1r-· r, 1 r,j,, n 1 ° .,, () 1--1 ri '1..,1 rip,..,. I(-'

- -- '-' ..._,.., \,.j '-' .,, \_, \_,. C 0. L :~ I I I i ':::1 . l t::; I :.:, I C; - .. _, :::_; t-' '-' ~ - ' . ,.. .


Examination of tissue specimens from 1918-1919 influenza fatalities. We reviewed hematoxylin and eosin-stained slides recut from blocks of lung

tissue obtained during autopsy from 58 influenza fatalities in 1918-1919.

These materials, sent during the pandemic from various United States

military bases to the National Tissue Repository of the Armed Forces

Institute of Pathology [8-10], represent all known influenza cases from this

collection for which lung tissue is available.

Pathology and bacteriology research records from the 1918-1919 influenza pandemic. We reviewed the late 19th- and early 20th-century

literature on gross and microscopic influenza pathology and bacteriology,

including evidence from 1918-1919 autopsy series with postmortem

cultures of lung tissue, blood samples (usually heart blood), pleural fluid,

and samples from other compartments. In an effort to obtain all

publications possibly reporting influenza pathology and/or bacteriology in

1918-1919, we searched major bibliographic sources [e.g., 11-17] for papers

in all languages and tables of contents of major journals in English, German,

and French; in addition, we searched all of the papers we identified for

additional citations. From more than 2000 such publications, we carefully

examined the 1539 reports that contained human pathologic and/or

bacteriologic findings (the full bibliographic list available at

httg:LLwww3.niaid.nih.govLtogicsLFluL1918LbibliograghY..htm), 109 of which

provided useful bacteriologic information derived from 173 autopsy series.

These series reported 8398 individual autopsy investigations undertaken in

15 countries, which can be characterized as follows: 96 postmortem lung

tissue culture series, 42 blood culture series, and 35 pleural fluid culture

series. When they were published as parts of an autopsy series, we

included in our analyses antemortem cultures of blood and pleural fluid

samples, which were mostly obtained during the terminal stages of illness.

A priori, we stratified data by military and civilian populations (see

Discussion), and by the quality of lung tissue culture results, considering to

be of "higher quality"; the 68 autopsy series with lung tissue culture results

that reported, for all autopsies, both the presence and absence of negative APPENDIX TO JAMES CASCIANO DECLARATION-236

culture results and the bacterial components of mixed culture results.

Results

Background epidemiologic data on influenza mortality rates in 1918-1919. Although death certificates listing cardiac and other chronic causes

of death increased in number during the time frame of the 1918-1919

pandemic [18], for all age groups death was predominantly associated with

pneumonia and related pulmonary complications [13, 14, 18-20]. The

pandemic caused a "W-shaped"; age-specific mortality curve, which

exhibited peaks in infancy, between about 20-40 years of age, and in

elderly individuals [3, 21]. In all age groups younger than "'65 years, the

influenza mortality rate was elevated beyond what would have been

expected on the basis of data from the previous pandemic of "Russian

influenza"; (1889-1893) [3, 22, 23]. The increased fatality rate in the 3

high-risk age groups was predominantly due to the increased frequency of

bronchopneumonia, not to increased incidence of influenza or an increased

bronchopneumonia case-fatality rate [19]. Because few autopsy reports

and, to our knowledge, no autopsy series addressed conditions other than

predominantly pulmonary complications, nonpulmonary causes of death are

not considered here.

Histologic examination of lung tissue from 1918 victims. The

examination of recut lung tissue sections from 1918-1919 influenza case

material revealed, in virtually all cases, compelling histologic evidence of

severe acute bacterial pneumonia, either as the predominant pathology or

in conjunction with underlying pathologic features now believed to be

associated with influenza virus infection [10, 24] (figure 1). The latter

include necrosis and desquamation of the respiratory epithelium of the

tracheobronchial and bronchiolar tree, dilation of alveolar ducts, hyaline

membranes, and evidence of bronchial and/or bronchiolar epithelial repair

[25, 26]. The majority of the cases examined demonstrated asynchronous

histopathological changes, in which the various stages of development of


the infectious process, from early bronchiolar changes to severe bacterial

parenchymal destruction, were noted in focal areas. The histologic

spectrum observed in the cases corresponded to the characteristic

pathology of bacterial pneumonia, including bronchopneumonia [10,24-33]:

lobar consolidation with pulmonary infiltration by neutrophils in

pneumococcal pneumonia; a bronchopneumonic pattern, edema, and

pleural effusions in streptococcal and sometimes in pneumococcal

pneumonia; and in staphylococcal pneumonia, multiple small abscesses

with a marked neutrophilic infiltration in airways and alveoli [27]. Bacteria

were commonly observed in the sections, often in massive numbers.

Figure 1

Examples of hematoxylin and eosin-stained postmortem lung sections from

4 victims of the 1918-1919 influenza pandemic (see text). A, Typical picture

of severe, widespread bacterial bronchopneumonia with transmural

infiltration of neutrophils in a bronchiole and with neutrophils filling the

airspaces of surrounding alveoli (original magnification, 40x). B, Massive


infiltration of neutrophils in the airspaces of alveoli associated with bacterial

bronchopneumonia as in A (original magnification, 200x). C,

Bronchopneumonia with intra-alveolar edema and hemorrhage. Numerous

bacteria are visible both in the edema fluid and in the cytoplasm of

macrophages (original magnification, 400x). D, Bronchopneumonia with

evidence of pulmonary repair. The alveolar epithelium is hyperplastic;

interstitial fibrosis is seen between alveoli (original magnification, 200x).

Published pathologic and/or bacteriologic findings from the 1918-1919 influenza pandemic. Although the cause of influenza was disputed in

1918, there was almost universal agreement among experts [e.g., 20, 27-33] that deaths were virtually never caused by the unidentified etiologic

agent itself, but resulted directly from severe secondary pneumonia caused

by well-known bacterial "pneumopathogens"; that colonized the upper

respiratory tract (predominantly pneumococci, streptococci, and

staphylococci). Without this secondary bacterial pneumonia, experts

generally believed that most patients would have recovered [20]. In type,

pattern, and case-fatality rate, influenza-associated bacterial pneumonia

was typical of pneumonia that was endemic during periods when influenza

was not prevalent [25, 28, 33, 34]. As described above, in cases for which a

single lung pathogen was recovered from culture, the anatomical

pathological type of the pneumonia usually corresponded to what was

expected. Bacteria were commonly observed in cases of pneumonia caused

by each of these pathogens. Such findings reflect the characteristic

pathology of bacterial pneumonia [10, 25, 27].

Surprising aspects of 1918-1919 influenza-associated pneumonia fatalities

included the following: (1) the high incidence of secondary pneumonia

associated with standard bacterial pneumopathogens; (2) the frequency of

pneumonia caused by both mixed pneumopathogens (particularly

pneumococci and streptococci) and by other mixed upper respiratory-tract

bacteria; (3) the aggressiveness of bacterial invasion of the lung, often

resulting in "phenomenal"; [30] numbers of bacteria and poly-


morphonuclear neutrophils, as well as extensive necrosis, vasculitis, and

hemorrhage [20, 32, 33]; and (4) the predominance of bronchopneumonia

and lobular pneumonia, as opposed to lobar pneumonia, consistent with

diffuse predisposing bronchiolar damage [27-33].

Contemporary views of the natural history of severe influenza during

the 1918-1919 influenza pandemic. By examining influenza autopsy

materials from a range of patients in different stages of disease,

pathologists in 1918-1919 identified the primary lesion in early severe

influenza-associated pneumonia as desquamative tracheobronchitis and

bronchiolitis extending diffusely over all or much of the pulmonary tree to

the alveolar ducts and alveoli, associated with sloughing of bronchiolar

epithelial cells to the basal layer, hyaline membrane formation in alveolar

ducts and alveoli, and ductal dilation [20, 24, 27, 29-33].

Primary "panbronchitis"; [35] was thought to reflect rapidly spreading

epithelial cytolytic infection of the entire bronchial tree [32, 35, 36]; this

was thought to have led to the secondary spread of enormous numbers of

bacteria along the denuded bronchial epithelium to every part of the

bronchial tree, following which focal bronchiolar infections broke through

into the lung parenchyma. Secondary bacterial invasion and zones of

vasculitis, capillary thrombosis, and necrosis surrounding areas of

bronchiolar damage were seen in severe cases. As was true for the 58

autopsy cases we reviewed (see above), published autopsies for victims of

the 1918-1919 pandemic generally showed histopathological asynchrony

[20]. Repair, represented by early epithelial regeneration, capillary repair,

and occasionally by fibrosis, was commonly seen in tissues sections from

even the most fulminant fatal cases [20, 27, 32]. Among the i=!=60% of

individuals who survived such severe pneumonia, severe chronic pulmonary

damage was apparently uncommon [37, 38].

Bacteriologic studies in autopsy series during the 1918-1919 influenza pandemic. Negative lung culture results were uncommon in the 96


identified military and civilian autopsy series, which examined 5266

subjects (4.2% of results overall) (table 1; full bibliographic list available at

hll~/./.www3.niaid.njh.gm,/.toP-ics/..Elu/1918/.bibliograP-b.y,htm). In the 68

higher-quality autopsy series, in which the possibility of unreported

negative cultures could be excluded, 92.7% of autopsy lung cultures were

positive for ~1 bacterium (table 1). Of these 96 series, 82 reported

pneumopathogens in ~50% of lungs examined, either alone or in mixed

culture results that included other bacteria (table 1). Outbreaks of

meningococcal pneumonia complicating influenza also were documented

[39]. Despite higher military case-fatality rates, the differences in the

frequency with which specific bacteria were isolated from lung tissue

cultures (table 1) and from culture of blood and pleural or empyema fluids

(data not shown) were minimal. Many of the series were methodologically

rigorous: in one study of approximately 9000 subjects who were followed

from clinical presentation with influenza to resolution or autopsy [40],

researchers obtained, with sterile technique, cultures of either

pneumococci or streptococci from 164 of 167 lung tissue samples. There

were 89 pure cultures of pneumococci; 19 cultures from which only

streptococci were recovered; 34 that yielded mixtures of pneumococci

and/or streptococci; 22 that yielded a mixture of pneumococci,

streptococci, and other organisms (prominently pneumococci and

nonhemolytic streptococci); and 3 that yielded nonhemolytic streptococci

alone. There were no negative lung culture results.

Table 1


,~ •'"41 cl at':urcs trom ~ 0f'9VJsm ~ JCClCh'CfOCJ. bv o,~"Hm

l.)c)o."'t1CC'..S

1~of No c:I ~ s~ ~ r.tr~ ~ ~ ~ ,_,

~sere, ,~, ~ ~t'leln ""1:'I.O ~ ~lt-c)gom ,,~ ... tuct(rd 1,i"Q•MI·

AO~t,, .. 60D 3.515 155CIU) 8151175) l&3(75J a,c, .11 101aon 38701 GI 481(138) 164CUJ A!I ovil,r, ,,. - ~ 1751 380 (11 71 21:11 I 11~ 0, 1GSl'9,ll 1 i••O II mm.7J 131i7 St 3l!)lt94, !,6 1371

AD l'ldlso,y Ol'.:I G¥61nln"'9(1) 6288 mllD.ll 8961170) 417(81) 41 «l.81 110SQ1.0I 619C9SI mnu~ 220'421

All ~- qu,a:,ty m,!,!..-y~

evo.en• ,,. - El:P 307~ 712123 21 s,sJ11ao, lJ:81711 ]1 -0 71 IZICKt, 1.c.4.4 71 lSJ 1!l ~., ]'}; 17 31

Pledoil1w•co ol pnau11iap;s!t11t9:1\!J

noc cordffllCd Ill • 14J 1115 2Wf187J 132111.13) 6164 7) OCOCJ 14021 :none.el CGICll,I) 88(7 7)

NOfl. ~ becter~ 8" L,ied ~ thcu (r)ml'l',c)l'I fWlme!I.., 1018 S~.,:, ~ w;,s CV!tJod ~ (,om,:,1~ ~t'tll!d W!'lh .,-1,x,ra '"'O t~ I

11. rlJ, 111. anl IV.~ IV wa11 oerc,,a:>a· tCIQUd0d M CClt\ta.n,,,g • nurrta of • ~ ~ • S.r~IOCO«ld ~u,Yh::v.i prClOltt\' co,•cr..oanck to St•~«~~, ~"' ~ ~ tno<it otnNwr1 ~'f'9.61N!d St~t ~ ,,om Sr~-w, ~ b.11 111 ~ c,~ otnr,,VOl'I .-.vfld o,-1y • S~ coco.,.· ~ ~ OS1C9J'll0d M ·~""5 • f4 tho ~t ~ o PlfhoQenc Ol'Q,1111'Sm ~"OOCl,S ,nr,.:-~GY" ,ne,ru1g1r,a,., OOf't!"'~ to·"-'-'-'"''"' ~~ ~ "'~#ccrtctspOnds to ~•\A~- Scio~• for~,. .&b>J. tM ·"uod ~~- rel ·at~ l:>.K~Cff.-·

C41e',1:IP~ Mv,,f 'Ofhcf. 0rVJ1":n>3 ¥«iro ~od>J "'11VP(!d ~ or'td W~ 8'Jlo lyptt 1'11S101fM g'c.,l,nt po,oarl-lge

' A hgt'crf qu&Uy terOI ~ dlrllflOd a!! II Ulf'tCI rtl W'\Cfl V'9 l,t:,1,1.a) CU!-J'lt •MU::t:. lc,portl:ld, fo, .0 D,rtopw,s, 1)():1"> t~• P,Moef"Ot ~ ~ of ~•v,,

et.lt'>'O ~ rd tho boct<W"..i ~h <:I m<a<'d c:tJlll'to r~i

Examples of hematoxylin and eosin-stained postmortem lung sections from

4 victims of the 1918-1919 influenza pandemic (see text). A, Typical picture

of severe, widespread bacterial bronchopneumonia with transmural

infiltration of neutrophils in a bronchiole and with neutrophils filling the

airspaces of surrounding alveoli (original magnification, 40x). B, Massive

infiltration of neutrophils in the airspaces of alveoli associated with bacterial

bronchopneumonia as in A (original magnification, 200x). C,

Bronchopneumonia with intra-alveolar edema and hemorrhage. Numerous

bacteria are visible both in the edema fluid and in the cytoplasm of

macrophages (original magnification, 400x). D, Bronchopneumonia with

evidence of pulmonary repair. The alveolar epithelium is hyperplastic;

interstitial fibrosis is seen between alveoli (original magnification, 200x).

In the 14 of 96 autopsy series that did not report the predominance of lung

pneumopathogens [29, 36, 41-53], pneumopathogens accounted

collectively for 37.4% of pneumonia deaths. The rest of the deaths were

associated collectively with either culture of nonpneumopathogenic "other

bacteria,"; such as nonhemolytic and viridans streptococci, "green

producing streptococci"; [54], probably largely corresponding to ahemolytic streptococci, uncharacterized diplostreptococci, Micrococcus

(Moraxella) catarrhs/is, Bacillus (Escherichia) coli, Klebsiella species, and

complex mixed bacteria (36.1% of cultures). Cultures also yielded Bacillus

influenzae (18.8%) and no bacterial growth (7.7%). These findings reflect


rates of bacterial isolation similar to those of the series that reported the

predominance of pneumopathogens (above and table 1), but with higher

isolation rates for "other bacteria"; offsetting the lower isolation rates for

pneumococci, streptococci and staphylococci. It is noteworthy that

pneumococcal typing antisera were unavailable in 11 of these 14 studies,

and that many of the cultured "other"; bacteria were reported as "gram

positive diplococci,"; "streptococci,"; or "diplostreptococci"; (data not

shown), consistent with the possibility that in this early era of bacterial

typing, some of the unidentified organisms in the culture may have been

pneumopathogens.

The predominant coinfecting microorganism in lung tissue cultures

containing ::::1 pneumopathogen was Bacillus inf/uenzae (largely

corresponding to the modern Hemophi/us inf/uenzae), an upper respiratory

tract organism not commonly found in pure culture of samples from any

anatomical compartment [20, 36, 55]. Bacillus influenzae tended to appear

early in symptomatic influenza in association with diffuse bronchitis and/or

bronchiolitis, sometimes infiltrating the bronchiolar submucosa [35]; it

caused seroconversion [56] and was then typically replaced by other

secondary organisms.

Cultures of blood samples in 30 military and 12 civilian series, which

examined a total of 1887 subjects (table 2), had positive results in 70.3% of

cases and typically contained either pneumococci or streptococci in pure

culture. Cultures of pleural or empyema fluid, reported in 23 military and 12

civilian series examining a total of 1245 subjects (table 2), revealed either

streptococci or pneumococci as the most commonly recovered organism in

all but 7 series: in 4 series mixed pneumopathogens predominated, and in 3

series Staphylococcus aureus predominated. Most subjects with positive

culture results in the blood and pleural or empyema fluid series also had ::::1

pneumopathogen cultured in samples from the lungs (data not shown).

Table 2


Blood~

Pkuat~o, ~Ouid ~(,ta 251 41mi'1ary4'1d

Nod ~ ~ ~

1887 !i09Q101

Ho f'J.l d QJ:110 trom W'ld, ~ Wi2S l'00IM70CI by ~'

~ s.~ ~ t'!::-~ Mtt'd S.':l!\A ~ OU't'l4 ~ ~ogr:rn r.'\A,WV ..

311,100, 681361 !,~lt nfll !.• 61 IJ'],

C:trtWl 124~ 163 rJ1 11 511 Ca.J) !.9 t.S 71 CH:> Ol

~ No ~., gn,.,,tt-.

1i'8l14 71 511129.7)

NOTE. fhc, ~ .. ,ro ~~cd by ti-cu o-.nm,or, ~'" ,~,e St•~-cv, ~ -· CU'l•.n>d .vd ,_,..,,..,n1-1 t,'IX'd v.i!h ~- IUl(J ~ I ti ~. 111. 11'112 IV. t)'PO I\' w.is ~,ay ~ ol!I ~~ • nun-w o1 · un~ ~ · Srrc,pflX'Oc'c:\.lj ~'-&'3 probltty corro--...i,ond:110 S:-~,1.11 ~"" mc:it caflCS. mtn1 ~I~ 5~ ~t,o,n S~ ~ b.d <fl~ C4~ ~Y(III raod 0My "Sr~ COCC\4 • ~ wo coteQOtllOd 4S ·...,~ • il !ho~<'•~ ~cd o Plthooc'n< 01Jll'I-~ D~ ~~• menng,r,a., cor.-e~ to -~!IC"'" """""~n6$ ~ ""~"" ODfr~ to ~~ ,r:!~JJC Soo AcMs to, drrt~s ~ tt-o 0

1"Fl,U1d ~~- rd "other t.Kt~.a· ~11:QO!'lftJ Mtt-'f -~. OI~'\ -(I ~fldlr IP!tvii,,d pr,cvn,)1JD0C> .,,_, )I':'~ 8d,j fvt1P ctwf.,QJf~ Q'C41MI po,o-r!...,..

Bacterial culture results in autopsy series involving 96 postmortem cultures

of lung tissue from victims of the 1918-1919 influenza pandemic.

Of 2007 pneumococcal isolates, 874 (43.5%) were serotyped by

agglutination. Type I was isolated from 124 (14.2%) of 874 subjects; type II

from 163 (18.6%); type Ila from 26 (3.0%); type Ill from 184 (21.1%); and

type IV, a category containing diverse and, at the time, untypeable

organisms, from 377 (43.1%).

Pathologic and bacteriologic information obtained from later pandemic and seasonal influenza cases. The viruses that caused the

1957 and 1968 pandemics were descendants of the 1918 virus in which 3

(the 1957 virus) or 2 (the 1968 virus) new avian gene segments had been

acquired by reassortment [21]. Although lower pathogenicity resulted in far

fewer deaths, hence fewer autopsies, most 1957-1958 deaths were

attributable to secondary bacterial pneumonia, as had been the case in

1918. Staphylococcus aureus, a relatively minor cause of the 1918 fatalities,

was predominant in the culture results from 1957-1958 [21, 57-61], and

negative lung tissue cultures were more common, possibly as a result of the

widespread administration of antibiotics [57, 58, 61]. The few relevant data

from the 1968-1969 pandemic (see below) are consistent with information

from the earlier 20th-century pandemics. Human tracheobronchial biopsy

studies performed since the 1957-1958 epidemic characterized the natural

history of influenza virus infection as featuring rapid (within 24 h)

development of bronchial epithelial necrosis, preservation of the basal layer, APPENDIX TO JAMES CASCIANO DECLARATION-244

limited inflammatory response, and evidence of prompt repair [62],

consistent with the observations of pathologists in 1918-1919.

Discussion

In the most recent influenza pandemic that did not involve the use of

antibiotics to suppress bacteria (the 1918-1919 pandemic), histological and

bacteriologic evidence suggests that the vast majority of influenza deaths

resulted from secondary bacterial pneumonia. Compelling evidence for this

conclusion includes the examination of 58 recut and restained autopsy

specimens that showed changes fully consistent with classical descriptions

of extensive bacterial pneumonia [25], culture results from numerous

international autopsy series, and consistent epidemiologic and clinical

findings (table 3).

Table3

MMt &iaoosie5 revealed 5eY8fO bact9fl41 pneumotli8 caused by common upoer •eflPtfatorv o,gan~m,. (20. 27-331

fn l\'PO, p,aftell\ and~ nato. ~ ~ ~ indudlng d'1oft:c lobar pnoumonra. was 1YPice' of Pft8UJTIOllia during periods when inftuonza wan not provatcnt bronchopnoumona essociaied wflh cMfuso -~diam.• p,odcm,,a:od 126. 28. 33. 34)

At iwtcp.sy. ca1ly anci,to, ~tem,vo ,ep.,11 of what aro now thought to be PoffliS1Y v.1B1 changos wcH e-.-cent. ~rQ

~ in pneumonia sun,n,o,s were maumal 120. 30. 32)

Pa2hoP.ogic 1rictUJo of bactoriDf ~ 4S30Ciatod With influonm in 1918-1919 Win~ &imiSar to 1tlo moro tuoM, C4tal mrns'st baaeri3t bf~~ of 1917-1918 l20. 27. 83)

Maced p,,ovmopaihogcn-auocaoted pnoumorua WH moro laial than ~thogcn pr,oumonia (191 Pno1,moma cmo, OJNbl'ted unit~ diffuso and axirm trecheobrond1i%i:9 andfor brondtio!itis. !he MMm!Y of

wflich ~ wiih pneumonia~ &n ctor,too end at'ltofflia1 Cocation 1291 Oemograph:c 4ndt'ot ep;dem~ evidenco

Most inftwnm CQSCS WCSO typal of Cl81I01J GOOtl todlJv: mid.~-and 8IIOCiutod wffll fufJ rocovory 113-171 M011al;fy at an OGM WM associoted wf1fl bxtetiol ~'° rates. not w,th 1nl'!uonza ou.ack rotes 0t P"N!'Umonltl

c,aw-fatohty raioo 119. 211 Ollrdtcft 6-16 Y83I& otct in 1918-1919 IIBd die hig!lest ot1t:d mt.es b1a ma 1owoat fflOltDlnv 1Btes. unmr m raw ma

vocn in 1889-1893 and imfflcdiatct, boforo and Gftor tho 1918-1919 ~ ~ ~ wiih wal wu1ance atone 114. 21,

tnfluonro-olSOQil!Od pnournoru,a inc:rdonco ratos and influenza death rutos Ytero S1Qndll:4tlt)v higher in US mdrta,v camp,, whd\ ~ bec'lef..,, ·coionll.at,on ~a· (631

A-. liino from lnflwnm onso1 co PftOUll'IOllm OMOt in &dtimltofy fotnl cnos c-10 dayiJ) may bo moso consistcn1 with bacteria1 than wal pneumoni3 1291

Troatrncft1 rosoons,o OYldenco The ftB31 tOW81S81 ab9cNation thal Stncl bed rest emt, in die caun!IO of liillCOIJdmted lftfluenm prevented

pneumonb Gftd cto=h is COMistlfflt .il'I an offoct of CICbtion from Cilfflef9 of bbctcrmJ pdioges1t 113. 141

Summary of evidence from the 1918-1919 influenza pandemic consistent

with the conclusion that bacterial pneumonia, rather than primary viral

pneumonia, was the cause of most deaths.


Between 1890 and 1950, most observers believed fatal influenza to be a

polymicrobial infection in which an inciting agent of low pathogenicity

(either a bacterium such as Bacillus influenzae or a "filter passing agent";

most of which have now been identified as viruses) acted synergistically

with known pneumopathogenic bacteria [13, 14, 20, 33, 64-66]. This view

was dramatically supported in 1917-1918 by the measles epidemics in US

Army training camps, in which most deaths resulted from streptococcal

pneumonia or, less commonly, pneumococcal pneumonia [20, 30, 32]. The

pneumonia deaths during the influenza pandemic in 1918 proved so highly

similar, pathologically, to the then-recent pneumonia deaths from the

measles epidemics that noted experts considered them to be the result of

one newly emerging disease: epidemic bacterial pneumonia precipitated by

prevalent respiratory tract agents [20, 33, 63].

The question of whether the pathogenesis of severe influenza-associated

pneumonia was primarily viral (i.e., assumed to be an unknown etiologic

agent in 1918) or a combination of viral and bacterial agents was carefully

considered by pathologists in 1918-1919, without definitive resolution [26,

33]. The issue was addressed anew in the early 1930s when Shope

published a series of experimental studies that involved the just-discovered

swine influenza A virus: severe disease in an animal model resulted only

when the virus and Hemophilus influenzae suis were administered together

[67]. In 1935, Brightman studied combined human influenza and

streptococcal infection in a ferret intranasal inoculation model. Even though

neither agent was pathogenic when administered alone, they were highly

fatal in combination [68]. In rhesus monkeys, human influenza viruses given

intranasally were not pathogenic, but could be made so by nasopharyngeal

instillation of otherwise nonpathogenic bacteria [69]. During the 1940s,

additional studies in ferrets, mice, and rats established that the influenza

virus in combination with any of several pneumopathic bacteria acted

synergistically to produce either a higher incidence of disease, a higher

death rate, or a shortened time to death [70-73]; these effects could be

mitigated or eliminated if antibiotics were given shortly after establishment


of combined infection [73]. More recent data suggest that influenza

vaccination may prevent bacterial disease [74].

As reviewed recently by McCullers [75], a body of experimental research

during the last 3 decades has identified possible mechanisms by which

coinfection with the influenza virus and bacteria might affect pathogenicity.

These include viral neuraminidase (NA)-induced exposure of bacterial

adherence receptors; bacterial NA-induced upregulation of influenza

infection; interleukin 10-induced susceptibility to pneumococci and possibly

staphylococci [76]; interferon type 1 effects [77]; viral PB1-F2 effects, the

proaptotic and mitochondriopathic effects of which are correlated with

enhanced bacterial infection [78]; and virus-induced desensitization to

bacterial Toll-like receptor ligands [79].

We believe that the weight of 90 years of evidence (table 3), including the

exceptional but largely forgotten work of an earlier generation of

pathologists, indicates that the vast majority of pulmonary deaths from

pandemic influenza viruses have resulted from poorly understood

interactions between the infecting virus and secondary infections due to

bacteria that colonize the upper respiratory tract. The data are consistent

with a natural history in which the virus, highly cytopathic to bronchial and

bronchiolar epithelial cells, extends rapidly and diffusely down the

respiratory tree, damages the epithelium sufficiently to break down the

mucociliary barrier to bacterial spread, and if able to gain access to the

distal respiratory tree-perhaps on the basis of receptor affinity [80]-creates

both a direct pathway for secondary bacterial spread and an environment

(cell necrosis and proteinaceous edema fluid) favorable to bacterial growth.

It remains unresolved whether cocolonizing, nonpneumopathic upper

respiratory-tract organisms such as Bacillus (Hemophi/us) influenzae play

an ancillary role, or are merely innocent bystanders. It is uncertain why

Hemophilus influenzae was much less prominent in 1957-1958 and

thereafter, but this phenomenon may relate to antibiotic use and

conceivably, in recent years, to Hemophilus influenzae b vaccination of


children.

The extraordinary severity of the 1918 pandemic remains unexplained. That

the causes of death included so many different bacteria, alone or in

complex combinations, argues against specific virulent bacterial clones.

The pathologic and bacteriologic data appear consistent with copathogenic

properties of the virus itself, perhaps related to viral growth, facility of cell

to-cell spread, cell tropism, or interference with or induction of immune

responses. Certain observers believed that cotransmission of the influenza

agent and of pneumopathogenic bacteria was responsible for many severe

and fatal cases, especially during the October-November 1918 peak of

mortality and case-fatality rates [81]. We speculate that any influenza virus

with an enhanced capacity to spread to and damage bronchial and/or

bronchiolar epithelial cells, even in the presence of an intact rapid

reparative response, could precipitate the appearance of severe and

potentially fatal bacterial pneumonia due to prevalent upper respiratory

tract bacteria.

In the modern era, the widespread use of antibiotics and the establishment

of life-prolonging intensive care unit treatment make it more difficult than it

was in 1918 to document the importance of bacterial lung infection for

influenza-related mortality. Influenza-associated pneumonia patterns may

now be influenced by the administration of pneumococcus, Hemophilus

influenzae b, and meningococcus vaccine, and cases have tended to occur

in elderly individuals, who rarely undergo autopsy. The 1968 influenza

pandemic was mild, and autopsy studies were uncommon [21]. Fatal cases

of influenza-associated viral pneumonia that are considered to be

"primary"; (i.e., with little or no bacterial growth) continue to be identified

[82, 83]; however, their incidence appears to be low, even in pandemic

peaks. The issue of the pathogenesis of fatal influenza-associated

pneumonia remains important; the fact that even severe, virus-induced

tissue damage is normally followed by rapid and extensive repair [20, 26]

suggests that early and aggressive treatment, including antibiotics and


intensive care, could save most patients [84, 85] and also underscores the

importance of prevention and prophylaxis.

The 1918 pandemic and subsequent pandemics differed with respect to the

spectrum and extent of secondary bacterial pneumonia {e.g., the switch in

prevalence during the antibiotic era to predominantly staphylococcal

secondary pneumonia, as opposed to streptococcal, pneumococcal, and

mixed secondary pneumonia; and the greatly decreased involvement of

Bacillus [Hemophilus] influenzae), suggesting that additional factors affect

the level of influenza morbidity and mortality. These might include the use

of antibiotics and antiviral agents, the rate of influenza vaccination and

bacterial vaccination, and demographic and social factors. The aging

population in the United States, the increasing number of persons living in

nursing home facilities, and the number of persons who are

immunosuppressed or affected by cardiac disease, renal disease, and/or

diabetes mellitus all represent potential factors that might change the

profile of morbidity and mortality during a future pandemic. for example,

elderly persons in nursing homes are at risk for pneumonia caused by

enteric organisms and sometimes by drug-resistant nosocomial organisms.

The spread of bacteria such as methicillin-resistant Staphylococcus aureus

and highly pathogenic clones of Streptococcus pyogenes pose more

general risks [86].

The viral etiology of and timing of the next influenza pandemic cannot be

predicted [87]. If, as some fear, a future pandemic is caused by a derivative

of the current highly pathogenic avian H5N1 virus, lessons from previous

pandemics may not be strictly applicable. Although histopathologic

information concerning current human H5N1 infections is sparse [10], its

pathogenic mechanisms may be atypical because the virus is poorly

adapted to humans [88] and because, in certain experimental animal

models [e.g., 89], some strains have induced severe pathology that differs

from the findings associated with circulating human influenza viruses

(which, in these models, cause disease resembling self-limited seasonal


influenza in humans [90]). However, if an H5N1 virus were to fully adapt to

humans, the clinicopathologic spectrum of associated disease could

become more like that of previous pandemics.

If the next pandemic is caused by a human-adapted virus similar to those

recognized since 1918, we believe the infection is likely to behave as it has

in past pandemics, precipitating severe disease associated with prevalent

colonizing bacteria. Recent reviews have discussed the importance of new

and improved influenza antiviral drugs and influenza vaccines in controlling

a pandemic [84, 91, 92]. The present work leads us to conclude that in

addition to these critical efforts, prevention, diagnosis, prophylaxis, and

treatment of bacterial pneumonia, as well as the stockpiling of antibiotics

and bacterial vaccines [84, 85, 93], should be among the highest priorities

in pandemic planning. We are encouraged that such considerations are

already being discussed and implemented by the agencies and individuals

responsible for such plans [94, 95].

Acknowledgments

We thank Betty Murgolo and the staff of the National Institutes of Health

(NIH) Library, for extensive research efforts in locating publications, and the

staff of the History of Medicine Division, National Library of Medicine, NIH,

for additional library research support. Wealso thank Cristina Cassetti, PhD,

and Andrea Scollard, DDS, PhD for translation of Italian language and

Portuguese language papers, respectively; Hillery A. Harvey, PhD, for

scientific assistance; and Gregory K. Folkers, MS, MPH, for helpful

discussion and editorial assistance. John J. McGowan, PhD, and the staff of

the National Institute of Allergy and Infectious Diseases (NIAID) Pandemic

Influenza Digital Archives project provided substantial assistance in

organizing and indexing historical manuscripts.

References


Financial support: Intramural Research Program of the National Institutes of Health; National Institute of Allergy and Infectious Diseases.

Presented in part: 2006 Annual Meeting of the American Epidemiological Society, Berkeley, California, 30 March, 2006; and 2007 Annual Meeting of the American Epidemiological Society, Boston, Massachusetts, 26 March 2007.

© 2008 by the Infectious Diseases Society of America


When Mask-Wearing Rules in the 1918 Pandemic Faced Resistance Most people complied, but some resisted (or poked holes in their masks to smoke).

BeckY. Little May 6, 2020

The influenza P-andemic of 1918 and 1919 was the most deadly flu outbreak in

history, killing up to 50 million people worldwide. In the United States, where it

ultimately killed around 675,000 people, local governments rolled out initiatives

to try to stop its spread. These varied by region, and included closing schools

and places of public amusement, enforcing "no-spitting" ordinances,

encouraging people to use handkerchiefs or disposable tissues and requiring

people to wear masks in public.

Mask-wearing ordinances mainly popped up in the western states, and it

appears most people complied with them. The nation was still fighting in World

War I, and officials framed anti-flu measures as a way to protect the troops from

the deadly outbreak.

WATCH: The Spanish Flu Was Deadlier Than WWI

The first recorded infection was in a U.S. Army private stationed at Fort Riley,

Kansas on March 4, 1918. Although the United States and the other nations at

war initially suppressed news of the flu (neutral Spain freely reported it, hence

the misnomer "Spanish flu"), there was a sense that following these new health

precautions was patriotic.

As one Red Cross PSA put it, "the man or woman or child who will not wear a

mask now is a dangerous slacker." This sense of wartime duty-and the fear of

being seen as a "slacker"-may have motivated those who complied with mask

orders in cities like San Francisco, Seattle, Denver and Phoenix.

Yet even though compliance was high, some complained that the masks were


uncomfortable, ineffective or bad for business. Officials were caught in public

without masks. And after the war ended, and there was no longer a sense that

people should wear masks to keep the troops safe, some dissenters even

formed an "Anti-Mask League" in San Francisco.

WATCH: World War I Documentaries on HISTORY Vault

Masks Were Made of Gauze or Even More Porous Material

Women working for the Red Cross make masks during the pandemic flu in 1918.

Bettmann Archive/Getty Images

In 1918, advanced masks like the N95s that healthcare workers use today were

a long way off. Surgical masks were made of gauze, and many people's flu

masks were made of gauze too. Red Cross volunteers made and distributed

many of these, and newspapers carried instructions for those who may want to make a mask for themselves or donate some to the troops. Still, not everyone

used the standard surgical design or material.

"To entice people to get them to wear them, [cities] were pretty lax in terms of


what people could wear," says J. Alex Navarro, assistant director of the Center

for the History of Medicine at the University of Michigan and one of the editors

in-chief of The American Influenza EP-.idemic of 1918-1919: A Digiral.

EncyQQpedia.

In October 1918, the Seattle Daily Times carried the headline "Influenza Veils

Set New Fashion: Seattle Women Wearing Fine Mesh With Chiffon Border to

Ward Off Malady." These "fashionable" masks and others made from dubious

material probably weren't helping much. Yet there was also debate within the

medical and scientific community about whether multiple-ply gauze masks

were effective either.

For instance, Detroit health commissioner J.W. Inches said gauze masks were

too porous to prevent the spread of the flu among the public. Also, masks are

most effective when worn properly, which wasn't always what happened. In

Phoenix, where most people apparently complied with the city's mask order,

some nonetheless Qoked holes in their masks to smoke-which greatly reduced

their effectiveness.

SEE PHOTOS: The 1918 Flu Camgaigns to Shame Peogle Into Following

New Rules

'Mask Slackers• Faced Enforcement, Punishment

Still, for the small percentage of people who went without a mask entirely,

reports suggest their issue had less to do with the science behind them, and

more to do with personal comfort.

"You read routinely about people not wanting to wear them because they're hot

and stuffy," says NancY. Bristow, chair of the history department at the

University of Puget Sound and author of American Pandemic: The Lost Worlds

of the 1918 Influenza EgJdemic. "Some people argue against them because they

say that they create fear in the public, and that we want to keep people calm;

which I think is really an excuse to critique them because someone doesn't

want to wear them."


PHOTOS: Innovative Ways Peogle Tried to Protect Themselves From the

Flu

Some businesses worried customers would shop less if they had to wear a

mask when they went outside, and some people claimed mask ordinances were

an infringement upon civil liberties. Yet "more important in terms of critiques,"

Bristow says, "is this idea that we've heard today as well that they give people a

false sense of security." As she points out, wearing a mask is less effective

when people don't follow other health guidelines too (and especially if some are

poking holes in their masks to smoke).

Cities that passed masking ordinances in the fall of 1918 struggled to enforce

them among the small portion of people who rebelled. Common punishments

were fines, prison sentences and having your name printed in the paper. In one

horrific incident in San Francisco, a special officer for the board of health shot a

man who refused to wear a mask as well as two bystanders.

This was far different from the treatment San Francisco's leaders received when

they didn't comply. At a boxing match, a police photographer captured images

of several supervisors, a congressman, a justice, a Navy rear-admiral, the city's APPENDIX TO JAMES CASCIANO DECLARATION-315

health officer and even the mayor, all without masks. The health officer paid a

$5 fine and the mayor later paid a $50 fine, but unlike other "mask slackers,~

they received no prison time (not to mention no one shot at them).

Mask-Wearing Declines After the War

A man receives a shave from a barber who wears a mask during the ongoing pandemic in Chicago, Illinois, circa 1918.

Chicago Sun-Times/Chicago Daily News Collection/Chicago History Museum/Getty Images

San Francisco's first masking order began in October and ended in November

after the World War I armistice. In January, when flu cases began to surge again

in San Francisco, the city implemented a second mask order. This time, the

resistance was much more intense. A group of dissenters that included a few

physicians and one member of the Board of Supervisors formed the "Anti-Mask

League," which held a public meeting with over 2,000 attendees.

Navarro speculates the resistance to San Francisco's second mask order may

have been more intense because the country was no longer at war, and some

residents didn't feel the same sense of patriotic duty they had before. In any

case, the city was an outlier. It doesn't appear that there were similar leagues or

protests in other cities.


Nanc~ Tomes, a distinguished professor of history at Stony Brook University

who has written about public health measures during the 1918-1919 flu

pandemic says while there were pockets of resistance to mask-wearing in 1918

and 1919, it was not widespread.

And, unlike handkerchiefs and paper tissues, which Tomes says people began

to use more regularly because of the pandemic, mask-wearing did not catch on

in the United States after the ordinances ended. It's still difficult to say how

effective mask-wearing on its own was in 1918 and 1919. What is clear is that

communities that implemented stronger health measures overall fared better

than those that didn't.

"Today we can look back and see that they flattened the curve and the

communities that did enforce much stricter regulations and for a longer period

of time and began earlier had lower death rates," Bristow says. "But they didn't

have that data tabulated yet, so I think in the aftermath it wasn't as clear that

what they had done had been effective."

Read more:

WhY. the Second Wave of the 1918 Sganish Flu Was So DeadlY.

Sganish Flu - Sv.mgtoms, How It Began & Ended

Amid 1918 Flu Pandemic, America Struggled to Burv. the Dead

WhY. October 1918 Was America's Deadliest Month Ever

Pandemics That Changed History: Iimeline



@ the University of Sao Paulo

DO FACEMASKS LIMIT THE CONTAMINATION/SPREAD OF RESPIRATORY

VIRUSES?

by admin-spiralab July 27, 2020

To limit the spread of respiratory diseases, facemasks can be used by:

- healthy people, avoiding thus contamination by infected individuals

- infected people, limiting the spread of viruses to susceptible individuals

The use of masks is intuitively logical, as it provides a barrier, preventing the spread of droplets

or aerosol containing viral particles. In fact, studies have shown that surgical masks or

respirators are able to retain a large part of the viruses expelled by infected people. Under ideal

conditions, which include the periodic replacement of surgical masks and receiving training for

proper aseptic techniques, masks can be effective in partially containing the transmission of

infectious agents. However, in the real world, where regular people without specific training

must in addition to acquiring an arsenal of surgical masks, remember to thoroughly wash their

hands before wearing a mask, not touching the mask with their hands, not removing it to have a

cup of coffee or enjoy a meal and then put them back on (these masks must be removed and

replaced with new ones), the efficiency of the masks drops tremendously.

The effectiveness of the use of masks as a tool to prevent the spread of respiratory diseases

among regular people (unlike health workers, who receive specific training and have many

masks at their disposal) has been tested in several uclinical trials". Such experiments have been

carried out over the past 15 years, some better conducted than others. A recent study,

published in 2020, compiled the results obtained in the best randomized clinical trials (RCTs) on

this topic (MacIntyre and Chughtai 2020). Randomized means that the individuals who

participated in these studies were divided into subgroups, made up of masked and unmasked

(control group) at random, but balanced in relation to general health condition, sex etc. RCTs

are the golden standard of clinical trials.


Seven studies have been carried out in which healthy individuals in the community wore masks

and another 3 studies in which a mask was worn by infected individuals. Each of these studies

typically involved many tens or even hundreds of people.

It should be noted that in all of these studies, the use of masks took place in the context of

closed places, be they households, student housing or hospitals. In none of these cases the use

of masks in public and open places has been tested. There is a good reason for this, as we will

see later on. Some of these studies tested the effectiveness of masks only, others tested the

effectiveness of masks+ hygiene measures, such as frequent hand washing.

In order to conclude on the effectiveness of masks as able to prevent the spread of respiratory

viruses, there must be a significantly lower number of secondary infections (people who

contract the virus from an infected household member) in the masked group than in the control

group.

In most studies in which masks were used by healthy people with the intention of protecting

them, susceptible individuals, by means of a mask, no statistically significant protective effect

was observed (5 out of 7 studies). That is, in these studies there was no clear difference between

the masked group and the control group. In two studies, a small statistically significant

difference was observed. In one of those (Cowling et al. 2009), there were 3 groups: the control

group, the hands hygiene group and the hands hygiene+ mask group. The hands hygiene group

displayed an odds ratio of 0.46 compared to the control group. This means that the chance of

those wearing masks getting contaminated was 0.46 times lower than that of the control group.

In other words, the chance of the unmasked group to contract the disease was 1 /0.46 = 2.17

times higher. The hand hygiene + masks group showed an odds ratio of 0.33, that is, mask

wearing decreased the risk by 0.13. Therefore, the chance of the hands hygiene+ mask group

for becoming sick was 3 times lower than that of the control group, while the chance of the

hands hygiene group (without masks) to get infected was 2.17 times less than that of the group

control. Clearly, the greatest benefit was frequent hand washing, while mask wearing conferred

a secondary contribution. Furthermore, according to this study, both interventions had a

positive effect if they were applied by the susceptible individuals within the first 36 hours from

the onset of symptoms of the infected individuals with who they were in contact.


Of the 7 studies mentioned above, this is the one that had the most statistically significant

results regarding the use of masks. The other studies displayed either negative results, or

positive outcomes but without statistical significance or other limitations. To see the references

cited in this article and a summary of their results can be found here.

A common, and to some extent correct claim is that facemasks should be worn by everyone in

order to prevent infected individuals (symptomatic, pre-symptomatic or asymptomatic) from

contaminating susceptible individuals. Three studies were carried out that tested this possibility.

One of these studies took place in France (Canini et al. 2010), involving 1 OS infected people. The

authors of this paper concluded that there was no difference between the control group and the

group in which infected people wore masks. In another study carried out in Saudi Arabia

(Barasheed et al. 2014), during the annual Islamic pilgrimage, it was found that the group that

wore masks infected 31 % of the people accommodated in the same tent, while in the control

tent, where the infected did not wear masks, that number rose to 53%. However, these data

were based on reports from the study participants who reported their own symptoms. When

the sick participants were tested for the presence of 5 types of viruses that could potentially

cause these symptoms, the difference between the groups disappeared. Thus, the symptoms

reported by the study participants could have been caused by other factors, other than the

viruses supposedly spread by the infected individuals (with or without masks).

Finally, in a study conducted in China (MacIntyre et al. 2016), 245 infected patients were divided

into 2 groups, with and without facemasks. The number of residents in the same household who

contracted the disease was assessed either by symptoms reporting or laboratory testing.

Infection rates measured by symptom reports showed a downward trend, but not statistically

significant when the facemasks and control groups were compared. However, the advantage of

the masked group was eliminated when the sick individuals were submitted to laboratory tests

to detect the presence of viruses. In this case, there was no difference between the groups.

APPENDIX TO JAMES CASCIANO DECL.ARATION-321

Two caveats must be stressed:

1-AII studies mentioned above involved tests in which individuals wore surgical masks or

respirators. None of them used cloth masks. There is a single RCT that tested the effectiveness

of cloth masks, in a hospital environment - {MacIntyre et al. 2015). Their conclusion is that these

masks should NOT be used in these environments. The group of healthcare workers who wore

cloth masks had a higher risk of contracting respiratory diseases than the control group that did

not wear any masks. ADDENDUM: A new paper {published on 7/21/2020 and not yet peer

reviewed) showed that cloth masks were completely inefficient in containing SARS-CoV-2

particles (Loupa et al. 2020).

2- No study has tested the use of masks in open spaces to limit the spread of respiratory

diseases in the outdoors. The reason for this is simple: the use of masks in open spaces is

unnecessary and defies the laws of microbiology. Viruses expelled by an individual in an open

environment either in the form of aerosol or small droplets are immediately diluted,

considerably reducing what virologists call "infectious dose" (the number of viruses required to

infect a healthy person). Microbiologists working with viruses know that one of the most efficient

ways to stop a viral infection is to dilute the viruses and host cells, which is a good analogy to

what happens in a dynamic open space - viruses spread (dilute) in the air as people walk by. In

addition, in the presence of solar radiation, RNA viruses such as SARS-Cov-2 are inactivated in a

matter of tens of minutes (Lytle and Sagripanti 2005). In other words, for a person to be infected

by viruses expelled by others in an open environment, there must be a great proximity between

them. Unless the infected person sneezes or coughs directly into the susceptible individual's

face, the risk of becoming infected outdoors is very low.

In conclusion, there is little reliable evidence that wearing masks, either by healthy people or by

infected individuals, has any consistent benefit in preventing respiratory disease. The authorities

should take these scientific data into account before decreeing the mandatory use of masks in

public spaces. The use of masks in open places, where there is no agglomeration (minimum

distance of 1 meter between people), as in streets, parks and beaches, defies the basic laws of

microbiology and should not be mandatory. In confined places such as buses, subways and

markets, wearing masks may be recommended.


References

Barasheed 0, Almasri N, Badahdah A-M, et al (2014) Pilot Randomised Controlled Trial to Test

Effectiveness of Facemasks in Preventing Influenza-like Illness Transmission among Australian

Hajj Pilgrims in 2011. Infect Disord Drug Targets 14:110-116.

https://doi.org/10.217/1871526514666141021112855

Bundgaard, H., Bundgaard, J. S., Raaschou-Pedersen, D. E.T., Mariager, AF., Schytte, N., von

Buchwald, C., ... & Benfield, T. (2020). Face masks for the prevention of COVID-19-Rationale and

design of the randomised controlled trial DANMASK-19. Dan Med}, 67, A05200363.

Canini L, Andreoletti L, Ferrari P, et al (2010) Surgical mask to prevent influenza transmission in

households: a cluster randomized trial. PloS One S:e13998.

https://doi.org/10.1371 /journal.pone.0013998

Cowling BJ, Chan K-H, Fang VJ, et al (2009) Facemasks and Hand Hygiene to Prevent Influenza

Transmission in Households. Ann Intern Med 151 :437-446. https://doi.org/10.7326/0003-4819-

151-7-200910060-00142

Glykeria Loupa, Dimitra Karali, SPYRIDON RAPSOMANIKIS. Aerosol filtering efficiency of

respiratory face masks used during the COVID-19 pandemic. medRxiv 2020.07.16.20155119; doi:

https://doi.org/10.1101 /2020.07.16.20155119

Lytle CD, Sagripanti J-L (2005) Predicted Inactivation of Viruses of Relevance to Biodefense by

Solar Radiation. J Virol 79: 14244-14252. https:/ /doi.org/10.1128/JVI. 79.22.14244- 14252.2005

MacIntyre CR, Chughtai AA (2020) A rapid systematic review of the efficacy of face masks and

respirators against coronaviruses and other respiratory transmissible viruses for the

community, healthcare workers and sick patients. Int J Nurs Stud 108:103629.

https://doi.org/10.1016/j.ijnurstu.2020.103629

MacIntyre CR, Seale H, Dung TC, et al (2015} A cluster randomised trial of cloth masks compared

with medical masks in healthcare workers. BMJ Open S:e006577.

https://doi.org/10.1136/bmjopen-2014-006577

MacIntyre CR, Zhang Y, Chughtai AA, et al (2016) Cluster randomised controlled trial to examine

medical mask use as source control for people with respiratory illness. BMJ Open 6:e012330.

https://doi.org/10.1136/bmjopen-2016-012330


Ragid Exgert Consultation on the Eff activeness of Fabric Masks for the C0VID-19 Pandemic (Agril 8, 2020)_ (2020) Consensus Study Report

National Academies of Sciences, Engineering, and Medicine

Contributors

Description

This rapid expert consultation responds to a request from the Office of

Science and Technology Policy (OSTP) concerning the effectiveness of

homemade fabric masks worn by the general public to protect others, as

distinct from protecting the wearer. The request stems from an interest in

reducing transmission within the community by individuals who are

infected, potentially contagious, but symptomatic or presymptomatic.

The National Academies of Sciences, Engineering, and Medicine convened

a standing committee of experts to help inform OSTP on critical science

and policy issues related to emerging infectious diseases and other public

health threats. The standing committee includes members with expertise in

emerging infectious diseases, public health, public health preparedness and

response, biological sciences, clinical care and crisis standards of care, risk

communication, and regulatory issues.

Topics

Health and Medicine - Infectious Disease

Health and Medicine - PolicY., Reviews and Evaluations


Suggested Citation

National Academies of Sciences, Engineering, and Medicine. 2020. Rapid

Expert Consultation on the Effectiveness of Fabric Masks for the COV/D-19

Pandemic (April 8, 2020). Washington, DC: The National Academies Press.

https://doi.org/10.17226/25776.

Import this citation to:

• Bibtex

• EndNote • Reference Manager

Publication Info

8 pages I 8.5 x 11

DO I: htt P-S :/./.do i. o rg/.1 0 .17 2 2 6 /.2 5 7 7 6


A Quantitative Assessment of the Total Inward Leakage of NaCl Aerosol Representing Submicron-Size Bioaerosol Through N95 Filtering Facepiece Respirators and Surgical Masks Respiratory protection provided by a particulate respirator is a function of

particle penetration through filter media and through faceseal leakage.

Faceseal leakage largely contributes to the penetration of particles through

a respirator and compromises protection. When faceseal leaks arise, filter

penetration is assumed to be negligible. The contribution of filter

penetration and faceseal leakage to total inward leakage (TIL) of

submicron-size bioaerosols is not well studied. To address this issue, TIL

values for two N95 filtering facepiece respirator (FFR) models and two

surgical mask (SM) models sealed to a manikin were measured at 8 L and

40 L breathing minute volumes with different artificial leak sizes. TIL values

for different size (20-800 nm, electrical mobility diameter) NaCl particles

representing submicron-size bioaerosols were measured using a scanning

mobility particle sizer. Efficiency of filtering devices was assessed by

measuring the penetration against NaCl aerosol similar to the method used

for NIOSH particulate filter certification. Results showed that the most

penetrating particle size (MPPS) was -45 nm for both N95 FFR models and

one of the two SM models, and -350 nm for the other SM model at sealed

condition with no leaks as well as with different leak sizes. TIL values

increased with increasing leak sizes and breathing minute volumes.

Relatively, higher efficiency N95 and SM models showed lower TIL values.

Filter efficiency of FFRs and SMs influenced the TIL at different flow rates

and leak sizes. Overall, the data indicate that good fitting higher-efficiency


FFRs may offer higher protection against submicron-size bioaerosols.

INTRODUCTION

Influenza and other pandemic infectious diseases cause illness and death

worldwide. The mode of transmission of infection appears to be through

large droplets, aerosols, fomites, or person-to-person contact. O Infected

subjects are known to release a wide size range of particles during

breathing, coughing, sneezing, and talking. The droplets travel some

distance and evaporate to form smaller-size particles. Normal human

subjects and infected individuals release considerable numbers of

submicron diameter particles in the exhaled breath.(-) In one study, exhaled

breath of seven subjects infected with influenza was collected on Teflon

filters and exhaled particle concentrations measured using an optical

particle counter. O Filters were tested for influenza virus by quantitative

polymerase chain reaction (qPCR). Results for four subjects showed

influenza virus particles in exhaled breath and over 87% of particles were

under 1 µm in diameter. Recently, appreciable numbers of influenza

particles were found in the ambient air in different locations. O Submicron

aerosols can remain airborne for prolonged periods because of their low

settling velocity. Infectious aerosol, when inhaled by susceptible persons, is

likely to cause disease.

Respiratory protection is known to reduce the inhalation of infectious

aerosols. The Centers for Disease Control and Prevention (CDC) has

developed recommendations on the use of the National Institute for

Occupational Safety and Health (NIOSH)-approved N95 filtering facepiece

respirators (FFRs) and facemasks for protection against pandemic influenza

virus transmission for home, community, and occupational settings. O SMs

are used as barriers to limit the dissemination of secretions or large droplets

from patient to others. The Food and Drug Administration (FDA) clears the

SMs for sale, based on the test report provided by the manufacturers. SMs

are confused with respirators because both look similar and are worn on the


face. In general, the filter efficiency of N95 FFRs is superior to SMs. (,) Filter

efficiency is enhanced by electrostatic charge on filter media of N95 FFRs.

The most penetrating particle size (MPPS) for N95 FFRs is -50 nm

(electrical mobility diameter). O In the case of SMs, both electrostatic as well

as mechanical (MPPS >100 nm) types are available.0 FFRs are fit-tested

before use in workplaces whereas SMs are not. SMs were used for

respiratory protection in health care facilities when there was a shortage of

respirators during pandemic seasons. 0 Therefore, knowing the

effectiveness of SMs against infectious bioaerosols is of public health

importance.

The effectiveness of N95 FFRs and SMs in health care settings has been

reviewed.(,) One study evaluated the health risk of nurses using respiratory

protection during the severe acute respiratory syndrome (SARS) epidemic

in Canada0 and showed that N95 respirators were more protective than the

SMs. Similarly, N95 respirators and hand washing were found to be

effective in protecting health care workers against SARS transmission. O

Another study reported a dramatic decrease of SARS infection from 52 to 8

among health care staff after implementation of the use of N95 masks,

gloves, and gowns. 0

Recently, the efficacy of N95 FF Rs or SMs against influenza transmission

was evaluated with human subjects exposed to live attenuated influenza

vaccine particles. O Analysis for influenza virus in the nasal washes of test

subjects by reverse transcription-polymerase chain reaction technique

showed that wearing N95 respirators offered a higher level of protection

than SMs. Another study measured the protection factor for SMs and FFRs

on test subjects in a controlled environmental test chamber and showed

that SMs may not be as protective as FFRs. O

Some studies have reported that SMs are as effective as N95 FFRs for

respiratory protection from viral respiratory pathogens.(-) Protection

performance was tested using a fluorescein-KCI aerosol spray onto the


faces of subjects wearing N95 FFRs or SMs and performing intermittent

exercises on a treadmill in a chamber. O Test aerosol size was assumed to be

about 0.1-0.3 µm based on the comparison of the filtration efficiency

obtained for N95 FFRs in their study with the efficiency reported by a

different group. O After the experiment, fluorescent stain on the faces and

KCI concentrations in different layers of FFRs and SMs were analyzed to

calculate the filter efficiency. Results showed that both N95 FFRs and SMs

gave 95% or greater filtration efficiency, and N95 FFRs had about 2%

filtration efficiency higher than the SMs indicating that SMs and N95 FFRs

can provide protection in a relatively low viral aerosol loading environment.

A case-control study in Hong Kong hospitals showed that both SMs and

N95 FFRs were significantly effective in reducing the risk of SARS infection

among staff. O In another study, influenza virus collected during coughing of

patients wearing N95 FFRs or SMs was analyzed by quantitative real time

RT-PCR.o The efficacy of SMs and N95 FFRs was found to be similar in

preventing the spread of influenza virus from patients. Similarly, the use of

SMs compared with N95 FFRs showed a non-inferior rate of laboratory

confirmed influenza. O

Comprehensive information on the relative efficacy of FFRs and SMs for

submicron-size bioaerosols is lacking. To address this issue, the Institute of

Medicine (IOM) recommended further research in key areas including the

effectiveness of facemasks and respirators against infectious particles and

faceseal leakage contributing to the overall total inward leakage (TIL). O TIL

is defined as an inverse function of a protection level offered by a respirator

when the contributions of aerosol penetration through filter media, faceseal

leakage, and leakage through other components are considered. It is known

that FFRs are designed to provide good fitting on the human face unlike the

SMs. Because of the difference in face-fitting characteristics, SMs will have

a larger faceseal leakage than FFRs when used by workers. One way to

compare the performance of FFRs with SMs is to measure the TIL under

controlled leak sizes.


In this study, TIL for two N95 FFR models and two SM models sealed to a

manikin was measured as a ratio of particle concentration inside the

breathing zone (space covered around the face by the filtering device) (Cin)

to outside (ambient) concentration (Cout) at different size artificial leak

holes introduced on the filtering devices at two different breathing flow

rates. Submicron diameter size NaCl aerosol was used to measure the TIL.

This size range of particles is similar to the size of bioaerosols released by

subjects under breathing conditions as reported previously.(-) Moreover,

TIL, a measure of filter penetration and faceseal leakage for submicron-size

particles would also be applicable to larger-size bioaerosols. TIL values for

the two N95 FFR models and the two SM models were compared. The

significance of filter penetration and faceseal leakage contributing to the

TIL, and the efficacy of N95 FFRs and SMs against submicron-size

bioaerosols are discussed.

Figure 1 Flow diagram of the manikin experimental setup used for submicron-size particle leakage under simulated breathing conditions (The rubber bladder mimics a human lung and allows breathing air to enter and exit through the mouth. A typical FFR with a sample probe and one leak probe is shown in the inset. The differential mobility analyzer (DMA) of the SMPS separates particles based on their electrical mobility.) (color figure available online)

Ill

MATERIALS AND METHODS

Filtering Facepiece Respirators (FFRs) and Surgical Masks (SMs)

Two NIOSH-approved N95 FFR models and two FDA-cleared SM models

were tested in the study. These models were selected based on their

performance in previous studies in our laboratory.(,) The manufacturers and

models (in parentheses) of the N95 FFRs were: Willson (model 1105N,) and


San Huei United Company (model 1895N,) labeled as N1 and N2, respectively, and the SM models were: Primed (model PG4-1073,) and 3M (model 1800) labeled as SM1 and SM2, respectively. None of the N95 models tested in the study had exhalation valves.

Filter Efficiency Test

Instantaneous filter penetration of FFRs and SMs was measured to assess their filter efficiency. Penetration of FFRs and SMs was measured using NaCl aerosol (count median diameter (CMD) 75±20 nm) generated by an Automated Filter Tester (AFT) TSI 8130 (TSI Inc., Shorewood, Minn.). O The

AFT measures penetration based on the light scattering of particles that pass through the filter. A Plexiglas test box (L 20 cm x W 20 cm x H 10 cm) with a top and bottom plate containing a hole (2.5 cm diameter) in the center was used for measuring aerosol penetration. O A FFR or SM with its concave side facing down was sealed to a Plexiglas plate (L 20 cm x W 20 cm x H 0.5 cm) using melted wax. A silicone sealant was used to seal the top and bottom plates to make the Plexiglas box airtight. The Plexiglas box containing the FFR or SM was placed between the two filter chucks of the AFT and aligned to keep the top and bottom plate holes facing the upstream and downstream filter chucks, respectively. Penetration was measured for 1 min at 85 L/min constant flow under airtight conditions by closing the filter chucks.

Total Inward Leakage Measurements Using a Manikin Setup

Figure 1 shows a manikin setup employed to evaluate the effect of faceseal leakage on TIL as described previously. O TIL was measured in two general configurations: (1) sealed to the manikin face with no artificial leaks induced through needles; and (2) sealed to the manikin face with artificial leaks induced through needles. A FFR or SM was sealed to a manikin head form using a silicone sealant and placed inside a test chamber (48 x 48 x


48 cm3). The head form was connected to a breathing simulator (Breathing

Simulator Series 1101, Hans Rudolph, Inc., Shawnee, Kans.) through an

isolation chamber consisting of a rubber bladder inside an airtight glass

container. A metal tube (2.5 cm diameter) from the back of the mouth was

connected to an inflatable rubber bladder, which mimics a human lung,

inside the glass container connected to a breathing simulator. The

breathing simulator allows air to go back and forth into the glass container.

In response, ambient air enters the bladder through the FFR sealed to the

manikin head form during inhalation and exits during exhalation. Thus, the

isolation chamber prevented particles created by the breathing simulator

pump from getting inside the breathing zone of the respirator. The

breathing simulator allowed for several parameters to be varied including

tidal volume and breathing rate, which provided simulation of more realistic

breathing conditions.

Table 1 Filter Penetration for the N95 FFR Models and SM Models at 85 L/min Constant Flow {Average of three samples {n = 3), error represents one standard deviation.)

NaCl aerosol used for TIL measurement was different from the aerosol used

for testing filter penetration. Size distribution of NaCl aerosol was obtained

in a manner similar to that described previously. O Briefly, polydisperse NaCl

aerosol was generated using a 1.5% NaCl solution with a constant output

atomizer (TSI 3076) and passed through a dryer, a 85 Kr charge neutralizer

(TSI model 3077A), diluted with 50 L/min of dry air passed through a high

efficiency particulate air filter (HEPA) and then into the test chamber (48 x

48 x 48 cm3; Figure 1). Excess aerosol exited through a hole (1.3 cm

diameter) in the back of the test chamber. A small fan was installed at the

bottom of the chamber to ensure an even distribution of particles

throughout. Aerosol samples from the test chamber were analyzed for

number concentration for different size monodisperse particles (20-

800 nm, electrical mobility diameter) over 240 sec and repeated after a 30

sec interval, using a scanning mobility particle sizer (SMPS) {TSI model APPENDIX TO JAMES CASCIANO DECLARATION-332

3080) with a long differential mobility analyzer (OMA), and an ultra-fine

condensation particle counter (UCPC, TSI 3776). The OMA separates

particles based on their electrical mobility. The count median diameter

(CMO) and mode size (peak size) of the test aerosols were obtained from

the SMPS scans.

The test FFR was equipped with a sample probe to measure aerosol

concentration inside the FFR and two leak probes to introduce artificial

leakage (Figure 1, lnset).O The leak probes (-3 mm diameter and -1 cm

long) were filled with non-hardening putty and increasing leak sizes were

obtained by carefully inserting hypodermic needles (16 and 13 gauge sizes

with inner diameters of 1.18 and 1.80 mm, respectively) through the putty to

provide consistent leak channels through the needles (-2.56 cm long). Care

was taken to ensure the needle was kept open after inserting it into the

putty. The tip of the needle was positioned proximately close to the inner

surface of the respirator. Because the above leak sizes did not produce a

significant difference in the TIL for SMs, larger leak sizes were used.

For comparison, SMs as well as FFRs were fixed with larger leak probes

(-3 mm diameter and -1 cm long). Each leak size was created using two

leak probes, one on each side. TIL was measured with three different leak

sizes (two 3 mm, four 3 mm or six 3 mm). Samples from inside and outside

the FFRs and SMs were withdrawn and analyzed by two SMPS systems

simultaneously. 0 The two SMPS systems scanned the particles in the 20-

800 nm size range three times each three min. Samples were withdrawn

simultaneously during manikin breathing at 8 and 40 L minute volumes with

tidal volumes of 0.5 and 1.5 L, respectively. These tidal volumes

corresponded to 16 and 26.7 breaths per minute, respectively. TIL was

calculated as the ratio of particle concentration inside (Cin) of the FFR or

SM to the outside concentration (Cout) and multiplied by 100%.

RESULTS


Filter Efficiency

NaCl aerosol penetrations for N95 FFR models were lower than the

penetrations for the SM models at 85 L/min flow rate (Table I). In addition,

penetrations for N1 and SM1 were relatively lower than the values obtained

for N2 and SM2, respectively. Based on the penetration values, N1 and SM1

are described as higher-efficiency FFR and SM models, respectively, throughout the article. Table 2

Table 2 Comparison of Total Inward Leakage (TIL) at Two Different Breathing Minute Volumes and Three Leak Sizes (Average of 4 samples (n = 4), error represents one standard deviation.)

Figure 2 Typical TIL values for the two N95 FFR models N1 and N2 at 8 L/min (left column) and 40 L/min (right column) breathing minute volumes (The symbols indicate sealed with no leaks(•), two 1.18 mm leaks (0), and two 1.80 mm leaks(•). The solid vertical line corresponds to the approximate MPPS (45 nm) of the two N95 FFR models. The dashed vertical line corresponds to the mode of the challenge aerosol (75 nm).)

ii]

TIL Measurement Under Breathing Conditions

The size distribution of NaCl aerosol used for TIL measurement showed a

CMD of -82 nm and a mode size (peak size) of -75 nm. Figure 2 shows the

TIL measured at no leak condition and with two small leak sizes at 8 L (left

panels) and at 40 L (right panels) breathing minute volumes for the two

N95 models. TIL for different size particles increased with increasing

breathing minute volumes from 8 to 40 L with no leaks. The most

penetrating particle size (MPPS) was -45 nm for both FFR models which

can be easily seen at 40 L breathing minute volume. With increasing leak APPENDIX TO JAMES CASCIANO DECLARATION-334

sizes (2x1.18 mm and 2x1.80 mm), the TIL for different size particles

increased for the two FFR models at both breathing rates. The MPPS

remained at -45 nm with different leak sizes. The TIL for the MPPS was

higher than the values for the other size particles. Among the two N95

models, N1 showed lower TIL values for different size particles than N2 at

both breathing rates.

Figure 3 shows an increase in the TIL for different size particles with

increasing leak sizes from 3 to 5 (2x3 mm, 4x3 mm, and 6x3 mm,

respectively) for both FFR models, at 8 and 40 L/min. Larger leak holes

(4x3 mm and 6x3 mm) tend to produce similar TIL values for different size

particles. Similar trends in TIL results were obtained for SM1 at different leak

sizes and flow rates (Figure 4, top panels). The MPPS was -45 nm with no

leaks and with a smaller leak size (2x3 mm), which can be seen at 40 L/min.

For SM2, however, TIL values for the various size particles at no leak

condition and with different induced leak sizes showed very little change at

both breathing flow rates (Figure 4, bottom panels). The MPPS for SM2 was

-350 nm at all test conditions. Table II shows the TIL for the two FFR

models and the two SM models at different leak sizes and flow rates.

Models N1, N2 and SM1 showed higher TIL values for 45 nm particles than

for 300 nm size particles at smaller leak sizes as reported previously. (24) For

SM2, however, TIL values were smaller at 45 nm than at 300 nm at all test

conditions.

Figure 3 Typical TIL values for the two N95 FFR models N1 and N2 at 8 L/min (left column) and 40 L/min (right column) breathing minute volumes (The symbols indicate: sealed with no leaks ( •), two 3 mm leaks (0), four 3 mm leaks(•), and six 3 mm leaks (4). The solid vertical line corresponds to the approximate MPPS (45 nm) of the two N95 FFR models. The dashed vertical line corresponds to the mode of the challenge aerosol [75 nm]).


Figure 4 Typical TIL values for the two surgical models SM1 and SM2 at

8 L/min (left column) and 40 L/min (right column) breathing minute volume (The symbols indicate: sealed with no leaks ( •), two 3 mm leaks (0), four 3 mm leaks(•), and six 3 mm leaks (a). The solid vertical line corresponds to the MPPS of ,v45 nm for SM1 and ,v350 nm for SM2 models. The dashed vertical line corresponds to the mode of the challenge aerosol [75 nm]).

DISCUSSION

TIL measured for 20-800 nm diameter size NaCl aerosols for the two N95

FFR models were lower than the values obtained for the two SM models at

the two different breathing flow rates without induced leaks. TIL value

without induced leaks represents penetration through filter media and

agrees with the trend in penetration measured at NIOSH certification test

condition. The inverse relationship between TIL and filter efficiency can also

be seen among the FFR models, N1 (higher efficiency) and N2 (lower

efficiency) as well as between the SM models, SM1 (higher efficiency) and

SM2 (lower efficiency). With increasing leak sizes, TIL for 20-800 nm size

particles increased with increasing breathing flow rates for both FFR models

as well as for the SM1 model. TIL values for the two FFR models were lower

than the values for the SM models at similar flow rates and leak sizes,

indicating the influence of filter efficiency. TIL values for the FFR models

and SM1 did not vary significantly at larger leak sizes where minimum

protection can be expected. However, TIL values between FFRs and SM2

were markedly different. Similar difference in TIL can also be seen between

SM1 and SM2. The results can be explained by the large difference in filter

efficiency between the filtering devices (FFRs and SM1 vs. SM2), and the

inverse relationship between efficiency and TIL.

Results obtained in the present study are consistent with the data for four

different N95 FFR models tested previously. O In that study, two relatively APPENDIX TO JAMES CASCIANO DECLARATION-336

higher-efficiency N95 FFR models showed lower TIL values than two lower

efficiency models with different leak sizes and flow rates. The inverse

relationship between filter efficiency and TIL provides a better explanation

for the higher levels of respiratory protection offered by the N95 FFRs than the SMs reported previously.(,,)

The MPPS was -45 nm for N1, N2, and SM1 models, and -350 nm for SM2

with no faceseal leakage. Similar results were obtained with smaller leak

sizes at different breathing rates. Results from the study indicated that FFRs

producing smaller TIL value at the MPPS may provide relatively higher

protection against submicron virus aerosols. Among the two SM models

tested, SM1 appears to be more effective than SM2 for submicron-size

virus aerosols.

The relative impact of filter penetration is believed to be minimal or

insignificant once leaks are introduced in the facemask. In this study,

artificial leaks introduced in the N95 FFRs and SMs sealed to the manikin

allowed the test aerosols (mode size -75 nm) to enter and exit the

breathing zone (space covered around the face by the filtering device)

during breathing flow conditions. Interestingly, the MPPS values for FFR and

SM models with induced leak sizes were similar to the MPPS obtained with

no leaks. The above phenomenon can be explained by the effect of filter

penetration or filter media characteristic regulating the concentration of

different size particles inside the FFR or SM sealed to the breathing manikin

at different leak sizes. The results are consistent with our previous finding0

that faceseal leakage acts as a gatekeeper and indiscriminately allows the

test aerosols to flow through the leaks and increases the concentration of

all size test aerosol inside the breathing zone, while filter penetration or

filter media characteristic assigns the TIL values for different size particles.

The results obtained in the study indicate that filter penetration potentially

influences the TIL of different size particles. The data provide a better

understanding on the contribution of faceseal leakage and filter penetration

to the overall TIL.


The contributions of filter penetration and faceseal leakage to the TIL

results obtained with the manikin raise the question of how well these

processes are represented when a respirator is worn by a human subject.

Faceseal leakage is known to be a major pathway that contributes to the TIL

of particles.(-) The number of particles penetrating through the faceseal

leakage pathway of the respirators and SMs tested on subjects has been

shown to far exceed the number of particles passing through the filter

medium. O The influence of filter penetration and faceseal leakage on the TIL

measured for test subjects has been described.(,) In one study, the overall

TIL values for Korean half-masks and three different class (top class, 1st

class, and 2nd class) FFR models donned on test subjects were measured.0

Among the FFRs, top class FFRs (~99% efficiency) showed average TIL

values of -5.0%. However, the TIL values for lower-efficiency FFRs ("1st

class'~ ~94% and "2nd class'~ ~80%) were -2 times higher than the TIL

values obtained for "top class" FFRs. Overall, the results indicated lower TIL

values for the higher-efficiency FFRs. This finding is supported by the data

obtained in our recent study on the inter-laboratory comparison of TIL

measurement. O Five different N95 FFR models with different filter

efficiencies were tested on 35 human subjects performing the Occupational

Safety and Health Administration (OSHA) fit-testing exercises in two

different test laboratories. A PortaCount Pro (TSI, Shorewood, Minn.)

measured the Cout /Cin ratio which was then converted to TIL values based

on the inverse relationship between the two parameters. Filter efficiency

was obtained only for four of the five models. Results showed that the

overall TIL values were lower for a relatively higher-efficiency N95 model,

and higher for three lower efficiency models in both laboratories. Moreover,

a good agreement between the two laboratories on the TIL values

measured for different N95 models was obtained, indicating the

measurement was reproducible. Filter efficiency dependence of TIL

obtained for human subjects in the above studies may explain the higher

protection offered by the N95 FFRs compared to the SMS in health care settings.(,,)


Filter efficiency of the N95 FFRs is generally higher than that of SMs

because of the difference in the filter media used for construction. The N95

FFRs are developed to meet more challenging test conditions than are the

SMs. Filter efficiency for N95 FFRs is >95% when tested using charge

neutralized NaCl aerosols with a CMD of 75±20 nm at 85 L/min. The

penetration level does not exceed 5%, up to 200 mg aerosol loading.

However, the performance among SMs may vary widely because of the far

less challenging test methods used for their clearance by the FDA. O

Filtration efficiency of high and moderate barrier SMs is >98% and low

barrier SMs is >95% based on the penetration measured against non

neutralized Staphylococcus aureus bacteria of 3000±300 nm at 28.3 L/min.

Some types of SMs are also tested with 100 nm diameter non-neutralized

polystyrene latex spheres (PSL) at 1 to 25 cm/sec face velocity which may

produce wide differences in their efficiencies. Non-neutralization of test

aerosol may overestimate the filter efficiency and partly contribute to the

enormous difference in the filter performance among SMs. (,) TIL is

dependent on efficiency of the filter device.(,) Because of the higher filter

efficiency, N95 FFRs are expected to show lower TIL values than do SMs as

described previously.(,)

Faceseal leakage is a major pathway for aerosol transport inside the filtering

device.(,) The SMs are not designed to provide a good fitting on a human

face that may allow more aerosol leakage. However, SMs were found to be

as effective as N95 FFRs against aerosol particles similar to the size of

infectious aerosols.(,,) In one study, the transmission of influenza during

routine health care activities by hospital nurses using N95 FFRs and SMs

was assessed. O These authors showed that SMs were equally effective in

preventing influenza virus transmission among health care workers. A

similar conclusion was obtained in other studies.(,) However, the

performance of N95 FFRs may be higher where considerable aerosol

generation can occur during procedures such as intubation or

bronchoscopy. O Other factors, including training and consistency in the use

of the device and concentration of aerosol exposure, can also influence the APPENDIX TO JAMES CASCIANO DECLARATION-339

overall effectiveness of protective devices.

A shortage of respiratory protection devices during pandemic diseases is

possible. To address the issue, the CDC has stockpiled large numbers of

them. Respirators were stockpiled based on several factors, including their

approval for use in health care facilities and availability in the market.

Results obtained in the present study may be important for this stockpiling.

For example, relatively higher efficiency N95 FFRs, as well as SMs, are

expected to produce lower TIL values representing higher protection

against infectious aerosols. This indicates that filter efficiency of respiratory

protection devices should also be considered for stockpiling purposes.

Limitations and Recommendations for Future Studies

The limitations of the current study include the small number of N95 FFR

and SM models tested for TIL measurement. Additional models, including

those equipped with an exhalation valve, need to be tested to obtain

conclusive information on filter efficiency dependence of TIL. Another

limitation of the study is the TIL measurement for particles below 800 nm

size range. TIL study for a wide size range of airborne particles using

additional equipment may provide more realistic information. Nevertheless,

the measurement for 20-800 nm size range provides the underlying

mechanism of regulation of TIL by filter penetration and faceseal leakage

processes. Further studies on TIL, using test subjects, are important to

evaluate the performance of N95 FFRs against submicron-size bioaerosols.

CONCLUSION

Filtration efficiencies of the two N95 FFRs were higher than those of the two

SMs tested in the study against NaCl aerosol. Efficiencies of N1and SM1

were relatively higher than those of N2 and SM2, respectively. TIL for NaCl

aerosol (CMD -82 nm) using a manikin setup showed a MPPS of -45 nm for

N95 FFR models N1 and N2 and SM1 models, and -350 nm for the SM2


model at different flow rates and leak sizes. Leakage of test aerosols

through artificial holes increased the TIL for different size particles while the

MPPS remained at the same sizes obtained at sealed condition with no

artificial leaks, showing that filter penetration regulates TIL. In general,

higher-efficiency N95 and SM models showed lower TIL values than the

lower-efficiency models, indicating the potential influence of filter

efficiency. TIL results obtained in the study indicate that faceseal leakage

allows all the different diameter size test aerosols to enter and exit the

filtering device while filter penetration assigns the TIL for different size

particles. Overall, the data suggest that higher-efficiency N95 FFRs with

good fitting characteristics would provide higher protection against

submicron-size bioaerosols.

ACKNOWLEDGMENTS

The authors acknowledge NIOSH colleagues including Christopher Coffey,

Ray Roberge, and Jay Parker for their useful suggestions and critical review

of the manuscript. This research work was supported by NIOSH funding.

DISCLAIMER

Mention of a commercial product or trade name does not constitute

endorsement by the National Institute for Occupational Safety and Health.

The findings and conclusions of this report are those of the authors and do

not necessarily represent the views of NIOSH. This article not subject to US

copyright law.


Mask use in the context of COVID-19

Interim guidance 1 December 2020

This document, which is an update of the guidance published on 5 June 2020, includes new scientific evidence relevant to the use of masks for reducing the spread of SARS-Co V-2, the virus that causes COVID-19, and practical considerations. It contains updated evidence and guidance on the following: • mask management; • SARS-CoV-2 transmission; • masking in health facilities in areas with community,

cluster and sporadic transmission; • mask use by the public in areas with community and

cluster transmission; • alternatives to non-medical masks for the public; • exhalation valves on respirators and non-medical masks; • mask use during vigorous intensity physical activity; • essential parameters to be considered when

manufacturing non-medical masks (Annex).

Key points

• The World Health Organization (WHO) advises the use of masks as part of a comprehensive package of prevention and control measures to limit the spread of SARS-CoV-2, the virus that causes COVID-19. A mask alone, even when it is used correctly, is insufficient to provide adequate protection or source control. Other infection prevention and control (IPC) measures include hand hygiene, physical distancing of at least I metre, avoidance of touching one's face, respiratory etiquette, adequate ventilation in indoor settings, testing, contact tracing, quarantine and isolation. Together these measures are critical to prevent human-to-human transmission ofSARS-CoV-2.

• Depending on the type, masks can be used either for protection of healthy persons or to prevent onward transmission (source control).

• WHO continues to advise that anyone suspected or confirmed of having COVID-19 or awaiting viral laboratory test results should wear a medical mask when in the presence of others (this does not apply to those awaiting a test prior to travel).

• For any mask type, appropriate use, storage and cleaning or disposal are essential to ensure that they are as effective as possible and to avoid an increased transmission risk.

Mask use in health care settings • WHO continues to recommend that health workers ( 1)

providing care to suspected or confirmed COVID-19

1 For adequate ventilation refer to regional or national institutions or heating, refrigerating and air-conditioning societies enacting ventilation requirements. Ifnot available or applicable, a

• World Heakh I Organization

patients wear the following types of mask/respirator in addition to other personal protective equipment that are part of standard, droplet and contact precautions:

- medical mask in the absence of aerosol generating procedures (AGPs)

- respirator, N95 or FFP2 or FFP3 standards, or equivalent in care settings for COVID-19 patients where AGPs are performed; these may be used by health workers when providing care to COVID-19 patients in other settings if they are widely available and if costs is not an issue.

• In areas of known or suspected community or cluster SARS-Co V-2 transmission WHO advises the following:

- universal masking for all persons ( staff, patients, visitors, service providers and others) within the health facility (including primary, secondary and tertiary care levels; outpatient care; and long-term care facilities)

- wearing of masks by inpatients when physical distancing of at least I metre cannot be maintained or when patients are outside of their care areas.

• In areas of known or suspected sporadic SARS-CoV-2 transmission, health workers working in clinical areas where patients are present should continuously wear a medical mask. This is known as targeted continuous medical masking for health workers in clinical areas;

• Exhalation valves on respirators are discouraged as they bypass the filtration function for exhaled air by the wearer.

Mask use in community settings • Decision makers should apply a risk-based approach

when considering the use of masks for the general public. • In areas of known or suspected community or cluster

SARS-Co V-2 transmission: - WHO advises that the general public should

wear a non-medical mask in indoor ( e.g. shops, shared workplaces, schools - see Table 2 for details) or outdoor settings where physical distancing of at least 1 metre cannot be maintained.

- If indoors, unless ventilation has been be assessed to be adequate 1, WHO advises that the general public should wear a non-medical mask, regardless of whether physical distancing of at least I metre can be maintained.

recommended ventilation rate of 10 1/s/person should be met (except healthcare facilities which have specific requirements). For more information consult "Coronavirus (COVID-19) response

Individuals/people with higher risk of severe complications from COVID-19 (individuals ~ 60 years old and those with underlying conditions such as cardiovascular disease or diabetes mellitus, chronic lung disease, cancer, cerebrovascular disease or immunosuppression) should wear medical masks when physical distancing of at least 1 metre cannot be maintained.

• In any transmission scenarios: - Caregivers or those sharing living space with

people with suspected or confirmed COVID-19, regardless of symptoms, should wear a medical mask when in the same room.

Mask use in children (2) • Children aged up to five years should not wear masks

for source control. • For children between six and 11 years of age, a risk

based approach should be applied to the decision to use a mask; factors to be considered in the risk-based approach include intensity of SARS-Co V-2 transmission, child's capacity to comply with the appropriate use of masks and availability of appropriate adult supervision, local social and cultural environment, and specific settings such as households with elderly relatives, or schools.

• Mask use in children and adolescents 12 years or older should follow the same principles as for adults.

• Special considerations are required for immunocompromised children or for paediatric patients with cystic fibrosis or certain other diseases (e.g., cancer), as well as for children of any age with developmental disorders, disabilities or other specific health conditions that might interfere with mask wearing.

Manufacturing of non-medical (fabric) masks (Annex) • Homemade fabric masks of three-layer structure (based

on the fabric used) are advised, with each layer providing a function: 1) an innermost layer of a hydrophilic material 2) an outermost layer made of hydrophobic material 3) a middle hydrophobic layer which has been shown to enhance filtration or retain droplets.

• Factory-made fabric masks should meet the minimum thresholds related to three essential parameters: filtration, breathability and fit.

• Exhalation valves are discouraged because they bypass the filtration function of the fabric mask rendering it unserviceable for source control.

Methodology for developing the guidance

Guidance and recommendations included in this document are based on published WHO guidelines (in particular the WHO Guidelines on infection prevention and control of epidemic- and pandemic-prone acute respiratory infections in health care) (2) and ongoing evaluations of all available scientific evidence by the WHO ad hoc COVID-19 Infection Prevention and Control Guidance Development Group (COVID-19 IPC GOG) (see acknowledgement section for list of GOG members). During emergencies WHO publishes interim guidance, the development of which follows a

resources from ASHRAE and others'' https://www.ashrae.org/technical-resources/resources

transparent and robust process of evaluation of the available evidence on benefits and harms. This evidence is evaluated through expedited systematic reviews and expert consensusbuilding through weekly GOG consultations, facilitated by a methodologist and, when necessary, followed up by surveys. This process also considers, as much as possible, potential resource implications, values and preferences, feasibility, equity, and ethics. Draft guidance documents are reviewed by an external review panel of experts prior to publication.

Purpose of the guidance

This document provides guidance for decision makers, public health and IPC professionals, health care managers and health workers in health care settings (including long-term care and residential), for the public and for manufactures of nonmedical masks (Annex). It will be revised as new evidence emerges.

WHO has also developed comprehensive guidance on IPC strategies for health care settings (3), long-term care facilities (LTCF) (4), and home care (5).

Background

The use of masks is part of a comprehensive package of prevention and control measures that can limit the spread of certain respiratory viral diseases, including COVID-19. Masks can be used for protection of healthy persons (worn to protect oneself when in contact with an infected individual) or for source control (worn by an infected individual to prevent onward transmission) or both.

However, the use of a mask alone, even when correctly used (see below), is insufficient to provide an adequate level of protection for an uninfected individual or prevent onward transmission from an infected individual (source control). Hand hygiene, physical distancing of at least 1 metre, respiratory etiquette, adequate ventilation in indoor settings, testing, contact tracing, quarantine, isolation and other infection prevention and control (IPC) measures are critical to prevent human-to-human transmission of SARS-Co V-2, whether or not masks are used ( 6).

Mask management

For any type of mask, appropriate use, storage and cleaning, or disposal are essential to ensure that they are as effective as possible and to avoid any increased risk of transmission. Adherence to correct mask management practices varies, reinforcing the need for appropriate messaging (7).

WHO provides the following guidance on the correct use of masks:

• Perform hand hygiene before putting on the mask. • Inspect the mask for tears or holes, and do not use a

damaged mask. • Place the mask carefully, ensuring it covers the mouth

and nose, adjust to the nose bridge and tie it securely to minimize any gaps between the face and the mask. If using ear loops, ensure these do not cross over as this widens the gap between the face and the mask.

• Avoid touching the mask while wearing it. If the mask is accidently touched, perform hand hygiene.

• Remove the mask using the appropriate technique. Do not touch the front of the mask, but rather untie it from behind.

• Replace the mask as soon as it becomes damp with a new clean, dry mask.

• Either discard the mask or place it in a clean plastic resealable bag where it is kept until it can be washed and cleaned. Do not store the mask around the arm or wrist or pull it down to rest around the chin or neck.

• Perform hand hygiene immediately afterward discarding a mask.

• Do not re-use single-use mask. • Discard single-use masks after each use and properly

dispose of them immediately upon removal. • Do not remove the mask to speak. • Do not share your mask with others. • Wash fabric masks in soap or detergent and preferably

hot water (at least 60° Centigrade/140° Fahrenheit) at least once a day. If it is not possible to wash the masks in hot water, then wash the mask in soap/detergent and room temperature water, followed by boiling the mask for 1 minute.

Scientific evidence

Transmission of the SARS-Co V-2 virus

Knowledge about transmission of the SARS-Co V-2 virus is evolving continuously as new evidence accumulates. COVID-19 is primarily a respiratory disease, and the clinical spectrum can range from no symptoms to severe acute respiratory illness, sepsis with organ dysfunction and death.

According to available evidence, SARS-CoV-2 mainly spreads between people when an infected person is in close contact with another person. Transmissibility of the virus depends on the amount of viable virus being shed and expelled by a person, the type of contact they have with others, the setting and what IPC measures are in place. The virus can spread from an infected person's mouth or nose in small liquid particles when the person coughs, sneezes, sings, breathes heavily or talks. These liquid particles are different sizes, ranging from larger 'respiratory droplets' to smaller 'aerosols.' Close-range contact ( typically within 1 metre) can result in inhalation of, or inoculation with, the virus through the mouth, nose or eyes (8-13).

There is limited evidence of transmission through fomites ( objects or materials that may be contaminated with viable virus, such as utensils and furniture or in health care settings a stethoscope or thermometer) in the immediate environment around the infected person (14-17). Nonetheless, fomite transmission is considered a possible mode of transmission for SARS-Co V-2, given consistent finding of environmental contamination in the vicinity of people infected with SARSCo V-2 and the fact that other coronaviruses and respiratory viruses can be transmitted this way (12).

Aerosol transmission can occur in specific situations in which procedures that generate aerosols are performed. The scientific community has been actively researching whether the SARS-CoV-2 virus might also spread through aerosol transmission in the absence of aerosol generating procedures (AGPs) ( 18, 19). Some studies that performed air sampling in

clinical settings where AGPs were not performed found virus RNA, but others did not. The presence of viral RNA is not the same as replication- and infection-competent (viable) virus that could be transmissible and capable of sufficient inoculum to initiate invasive infection. A limited number of studies have isolated viable SARS-Co V-2 from air samples in the vicinity of COVID-19 patients (20, 21 ).

Outside of medical facilities, in addition to droplet and fomite transmission, aerosol transmission can occur in specific settings and circumstances, particularly in indoor, crowded and inadequately ventilated spaces, where infected persons spend long periods of time with others. Studies have suggested these can include restaurants, choir practices, fitness classes, nightclubs, offices and places of worship (12).

High quality research is required to address the knowledge gaps related to modes of transmission, infectious dose and settings in which transmission can be amplified. Currently, studies are underway to better understand the conditions in which aerosol transmission or superspreading events may occur.

Current evidence suggests that people infected with SARSCo V-2 can transmit the virus whether they have symptoms or not. However, data from viral shedding studies suggest that infected individuals have highest viral loads just before or around the time they develop symptoms and during the first 5-7 days of illness ( 12). Among symptomatic patients, the duration of infectious virus shedding has been estimated at 8 days from the onset of symptoms (22-24) for patients with mild disease, and longer for severely ill patients (12). The period of infectiousness is shorter than the duration of detectable RNA shedding, which can last many weeks ( 17).

The incubation period for COVID-19, which is the time between exposure to the virus and symptom onset, is on average 5-6 days, but can be as long as 14 days (25, 26).

Pre-symptomatic transmission - from people who are infected and shedding virus but have not yet developed symptoms - can occur. Available data suggest that some people who have been exposed to the virus can test positive for SARS-CoV-2 via polymerase chain reaction (PCR) testing 1-3 days before they develop symptoms (27). People who develop symptoms appear to have high viral loads on or just prior to the day of symptom onset, relative to later on in their infection (28).

Asymptomatic transmission - transmission from people infected with SARS-CoV-2 who never develop symptoms -can occur. One systematic review of 79 studies found that 20% (17-25%) of people remained asymptomatic throughout the course of infection. (28). Another systematic review, which included 13 studies considered to be at low risk of bias, estimated that 17% of cases remain asymptomatic ( 14%-20%) (30). Viable virus has been isolated from specimens of presymptomatic and asymptomatic individuals, suggesting that people who do not have symptoms may be able to transmit the virus to others. (25, 29-37)

Studies suggest that asymptomatically infected individuals are less likely to transmit the virus than those who develop symptoms (29). A systematic review concluded that individuals who are asymptomatic are responsible for transmitting fewer infections than symptomatic and presymptomatic cases (38). One meta-analysis estimated that there is a 42% lower relative risk of asymptomatic transmission compared to symptomatic transmission (30).

Guidance on mask use in health care settings

Masks for use in health care settings

Medical masks are defined as surgical or procedure masks that are flat or pleated. They are affixed to the head with straps that go around the ears or head or both. Their performance characteristics are tested according to a set of standardized test methods (ASTM F2100, EN 14683, or equivalent) that aim to balance high filtration, adequate breathability and optionally, fluid penetration resistance (39, 40).

Filteringfacepiece respirators (FFR), or respirators, offer a balance of filtration and breathability. However, whereas medical masks filter 3 micrometre droplets, respirators must filter more challenging 0.075 micrometre solid particles. European FFRs, according to standard EN 149, at FFP2 performance there is filtration of at least 94% solid NaCl particles and oil droplets. US N95 FFRs, according to NIOSH 42 CFR Part 84, filter at least 95% NaCl particles. Certified FFRs must also ensure unhindered breathing with maximum resistance during inhalation and exhalation. Another important difference between FFRs and other masks is the way filtration is tested. Medical mask filtration tests are performed on a cross-section of the masks, whereas FFRs are tested for filtration across the entire surface. Therefore, the layers of the filtration material and the FFR shape, which ensure the outer edges of the FFR seal around wearer's face, result in guaranteed filtration as claimed. Medical masks, by contrast, have an open shape and potentially leaking structure. Other FFR performance requirements include being within specified parameters for maximum CO2 build up, total inward leakage and tensile strength of straps ( 41, 42).

A. Guidance on the use of medical masks and respirators to provide care to suspected or confirmed COVID-19 cases

Evidence on the use of mask in health care settings

Systematic reviews have reported that the use of N95/P2 respirators compared with the use of medical masks (see mask definitions, above) is not associated with statistically significant differences for the outcomes of health workers acquiring clinical respiratory illness, influenza-like illness (risk ratio 0.83, 95%CI 0.63-1.08) or laboratory-confirmed influenza (risk ratio 1.02, 95%CI 0.73-1.43); harms were poorly reported and limited to discom~ort associate~ with lower compliance (43, 44). In many settmgs, preservmg the supply of N95 respirators for high-risk, aerosol-generating procedures is an important consideration ( 45).

A systematic review of observational studies on the betacoronaviruses that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and COVID-19 found that the use of face protection (including respirators and medical masks) is associated with reduced risk of infection among health workers. These studies suggested that N95 or similar respirators might be associated with greater reduction in risk than medical or 12-16-layer cotton masks. However, these studies had important

2 The WHO list of AGPs includes tracheal intubation, non-invasive ventilation, tracheotomy, cardiopulmonary resuscitation, manual

limitations (recall bias, limited information about the situations when respirators were used and limited ability to measure exposures), and very few studies included in the review evaluated the transmission risk of COVID-19 ( 46). Most of the studies were conducted in settings in which AGPs were performed or other high-risk settings ( e.g., intensive care units or where there was exposure to infected patients and health workers were not wearing adequate PPE).

WHO continues to evaluate the evidence on the effectiveness of the use of different masks and their potential harms, risks and disadvantages, as well as their combination with hand hygiene, physical distancing of at least I metre and other IPC measures.

Guidance

WHO's guidance on the type of respiratory protection to be worn by health workers providing care to COVID-19 patients is based on I) WHO recommendations on IPC for epidemicand pandemic-prone acute respiratory infections in health care (47); 2) updated systematic reviews of randomized controlled trials on the effectiveness of medical masks compared to that of respirators for reducing the risk of clinical respiratory illness, influenza-like illness (ILi) and laboratoryconfirmed influenza or viral infections. WHO guidance in this area is aligned with guidelines of other professional organizations, including the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, and the Infectious Diseases Society of America ( 48, 49). ·

The WHO COVID-19 IPC GOG considered all available evidence on the modes of transmission of SARS-Co V-2 and on the effectiveness of medical mask versus respirator use to protect health workers from infection and the potential for harms such as skin conditions or breathing difficulties.

Other considerations included availability of medical masks versus respirators, cost and procurement implications and equity of access by health workers across different settings.

The majority (71%) of the GOG members confirmed their support for previous recommendations issued by WHO on 5 June 2020: 1. In the absence of aerosol generating procedures (AGPs)2,

WHO recommends that health workers providing care to patients with suspected or confirmed COVID-19 should wear a medical mask (in addition to other PPE that are part of droplet and contact precautions).

2. In care settings for COVID-19 patients where AGPs are performed, WHO recommends that health workers should wear a respirator (N95 or FFP2 or FFP3 standard, or equivalent) in addition to other PPE that are part of airborne and contact precautions.

In general, health workers have strong preferences about having the highest perceived protection possible to prevent COVID-19 infection and therefore may place high value on the potential benefits of respirators in settings without AGPs. WHO recommends respirators primarily for settings where AGPs are performed; however, if health workers prefer them and they are sufficiently available and cost is not ~ issu~, they could also be used during care for COVID-19 patients m other settings. For additional guidance on PPE, including PPE

ventilation before intubation, bronchoscopy, sputum induction using nebulized hypertonic saline, and dentistry and autopsy procedures.

beyond mask use by health workers, see WHO IPC guidance during health care when COVID-19 infection is suspected (3) and also WHO guidance on the rational use of PPE (45).

Exhalation valves on respirators are discouraged as they bypass the filtration function for exhaled air.

B. Guidance on the use of mask by health workers, caregivers and others based on transmission scenario

Definitions

Universal masking in health facilities is defined as the requirement for all persons (staff, patients, visitors, service providers and others) to wear a mask at all times except for when eating or drinking.

Targeted continuous medical mask use is defined as the practice of wearing a medical mask by all health workers and caregivers working in clinical areas during all routine activities throughout the entire shift.

Health workers are all people primarily engaged in actions with the primary intent of enhancing health. Examples are: nursing and midwifery professionals, doctors, cleaners, other staff who work in health facilities, social workers, and community health workers.

Evidence on universal masking in health care settings

In areas where there is community transmission or large-scale outbreaks of COVID-19, universal masking has been adopted in many hospitals to reduce the potential of transmission by health workers to patients, to other staff and anyone else entering the facility (50).

Two studies found that implementation of a universal masking policy in hospital systems was associated with decreased risk of healthcare-acquired SARS-Co V-2 infection. However, these studies had serious limitations: both were before-after studies describing a single example of a phenomenon before and after an event of interest, with no concurrent control group, and other infection control measures were not controlled for (51, 52). In addition, observed decreases in health worker infections occurred too quickly to be attributable to the universal masking policy.

Guidance

Although more research on universal masking in heath settings is needed, it is the expert opinion of the majority (79%) of WHO COVID-19 IPC GOG members that universal masking is advisable in geographic settings where there is known or suspected community or cluster transmission of the SARS-Co V-2 virus. 1. In areas of known or suspected community or cluster

SARS-Co V-2 transmission, universal masking should be advised in all health facilities (see Table 1 ).

• All health workers, including community health workers and caregivers, should wear a medical mask at all times, for any activity ( care of COVID-19 or nonCOVID-19 patients) and in any common area (e.g., cafeteria, staff rooms).

• Other staff, visitors, outpatients and service providers should also wear a mask (medical or non-medical) at all times

• Inpatients are not required to wear a mask (medical or non-medical) unless physical distancing of at least 1 metre cannot be maintained ( e.g., when being examined or visited at the bedside) or when outside of their care area ( e.g., when being transported).

• Masks should be changed when they become soiled, wet or damaged or if the health worker/caregiver removes the mask ( e.g., for eating or drinking or caring for a patient who requires droplet/contact precautions for reasons other than COVID-19).

2. In the context of known or suspected sporadic SARSCo V-2 virus transmission, WHO provides the following guidance:

• Health workers, including community health workers and caregivers who work in clinical areas, should continuously wear a medical mask during routine activities throughout the entire shift, apart from when eating and drinking and changing their medical masks after caring for a patient who requires droplet/contact precautions for other reasons. In all cases, medical masks must be changed when wet, soiled, or damaged; used medical masks should be properly disposed of at the end of the shift; and new clean ones should be used for the next shift or when medical masks are changed.

• It is particularly important to adopt the continuous use of masks in potentially high transmission risk settings including triage, family physician/general practitioner offices; outpatient departments; emergency rooms; COVID-19 designated units; haematology, oncology and transplant units; and long-term health and residential facilities.

• Staff who do not work in clinical areas ( e.g., administrative staff) do not need to wear a medical mask during routine activities if they have no exposure to patients.

Whether using masks for universal masking within health facilities or targeted continuous medical mask use throughout the entire shift, health workers should ensure the following:

• Medical mask use should be combined with other measures including frequent hand hygiene and physical distancing among health workers in shared and crowded places such as cafeterias, break rooms, and dressing rooms.

• The medical mask should be changed when wet, soiled, or damaged.

• The medical mask should not be touched to adjust it or if displaced from the face for any reason. If this happens, the mask should be safely removed and replaced, and hand hygiene performed.

• The medical mask ( as well as other personal protective equipment) should be discarded and changed after caring for any patient who requires contact/droplet precautions for other pathogens, followed by hand hygiene.

• Under no circumstances should medical masks be shared between health workers or between others wearing them. Masks should be appropriately disposed of whenever removed and not reused.

• A particulate respirator at least as protective as a United States of America (US) National Institute for Occupational Safety and Health-certified N95, N99, US Food and Drug Administration surgical N95, European Union standard FFP2 or FFP3, or equivalent, should be worn in settings for COVID-19 patients where AGPs are perfonned (see WHO recommendations below). In these settings, this includes continuous use by health workers throughout the entire shift, when this policy is implemented.

Note: Decision makers may consider the transmission intensity in the catchment area of the health facility or community setting and the feasibility of implementing a universal masking policy compared to a policy based on assessed or presumed exposure risk. Decisions need to take into account procurement, sustainability and costs of the policy. When planning masks for all health workers, longtenn availability of adequate medical masks (and when applicable, respirators) for all workers should be ensured, in particular for those providing care for patients with confinned or suspected COVID-19. Proper use and adequate waste management should be ensured.

The potential harms and risks of mask and respirator use in the health facility setting include:

• contamination of the mask due to its manipulation by contaminated hands (53, 54);

• potential self-contamination that can occur if medical masks are not changed when wet, soiled or damaged; or by frequent touching/adjusting when worn for prolonged periods (55);

• possible development of facial skin lesions, irritant dennatitis or worsening acne, when used frequently for long hours (56-58);

• discomfort, facial temperature changes and headaches from mask wearing (44, 59, 60);

• false sense of security leading potentially to reduced adherence to well recognized preventive measures such as physical distancing and hand hygiene; and risk-taking behaviours ( 61-64 );

• difficulty wearing a mask in hot and humid environments • possible risk of stock depletion due to widespread use in

the context of universal masking and targeted continuous mask use and consequent scarcity or unavailability for health workers caring for COVID 19 patients and during health care interactions with non-COVID-19 patients where medical masks or respirators might be required.

Alternatives to medical masks in health care settings

The WHO's disease commodity package (DCP) for COVID-19 recommends medical masks for health workers to be type II or higher (65). Type II medical masks provide a physical barrier to fluids and particulate materials and have bacterial filtration efficiency of ~8% compared to Type I mask, which has bacterial filtration efficiency of ::::95% and lower fluid resistance ( 66) In case of stock outs of type II or higher medical masks, health workers should use a type I medical mask as an alternative. Other alternatives such as face shields or fabric masks should be carefully evaluated.

Face shields are designed to provide protection from splashes of biological fluid (particularly respiratory secretions), chemical agents and debris (67, 68) into the eyes. In the context of protection from SARS-CoV-2 transmission through respiratory droplets, face shields are used by health workers as personal protective equipment (PPE) for eye protection in combination with a medical mask or a respirator (69, 70) While a face shield may confer partial protection of the facial area against respiratory droplets, these and smaller droplets may come into contact with mucous membranes or with the eyes from the open gaps between the visor and the face (71,67).

Fabric masks are not regulated as protective masks or part of the PPE directive. They vary in quality and are not subject to mandatory testing or common standards and as such are not considered an appropriate alternative to medical masks for protection of health workers. One study that evaluated the use of cloth masks in a health care facility found that health care workers using 2 ply cotton cloth masks (a type of fabric mask) were at increased risk of influenza-like illness compared with those who wore medical masks (72).

In the context of severe medical mask shortage, face shields alone or in combination with fabric mask may be considered as a last resort (73). Ensure proper design of face shields to cover the sides of the face and below the chin.

As for other PPE items, if production of fabric masks for use in health care settings is proposed locally in situations of shortage or stock out, a local authority should assess the product according to specific minimum perfonnance standards and required technical specifications (see Annex).

Additional considerations for community care settings

Like other health workers, community health workers should apply standard precautions for all patients at all times, with particular emphasis regarding hand and respiratory hygiene, surface and environmental cleaning and disinfection and the appropriate use of PPE. When a patient is suspected or confinned of having COVID-19, community health workers should always apply contact and droplet precautions. These include the use of a medical mask, gown, gloves and eye protection (7 4 ).

IPC measures that are needed will depend on the local COVID-19 transmission dynamics and the type of contact required by the health care activity (see Table 1). The community health workforce should ensure that patients and workforce members apply precautionary measures such as respiratory hygiene and physical distancing of at least 1 metre (3.3 feet). They also may support set-up and maintenance of hand hygiene stations and community education (74). In the context of known or suspected community or cluster transmission, community health workers should wear a medical mask when providing essential routine services (see Table 1).

Table 1. Mask use in health care settings depending on transmission scenario, target population, setting, activity and type*

Transmission Target population Setting (where) Activity (what) Mask type (which scenario (who) one)*

Known or Health workers and Health facility For any activity in patient-care Medical mask ( or suspected caregivers (including primary, areas (COVID-19 or non- respirator if aerosol community or secondary, tertiary care COVID-19 patients) or in any generating cluster levels, outpatient care, common areas ( e.g., cafeteria, procedures transmission and long-term care staff rooms) performed) ofSARS- Other staff, patients, facilities) For any activity or in any Medical or fabric CoV-2 visitors, service common area mask

suppliers

Inpatients In single or multiple- When physical distance of at bed rooms least I metre cannot be

maintained

Health workers and Home visit (for When in direct contact with a Medical mask caregivers example, for antenatal patient or when a distance of at

or postnatal care, or for least I metre cannot be a chronic condition) maintained.

Community Community outreach programmes/essential routine services

Known or Health workers and Health facility In patient care area- irrespective Medical mask suspected caregivers (including primary, of whether patients have sporadic secondary, tertiary care suspected/confirmed COVID-19 transmission Other staff, patients, levels, outpatient care, No routine activities in patient Medical mask not ofSARS- visitors, service and long-term care areas required. Medical CoV-2 cases suppliers and all others facilities) mask should be

worn if in contact or within I metre of patients, or according to local risk assessment

Health workers and Home visit ( for When in direct contact or when a Medical mask caregivers example, for antenatal distance of at least I metre

or postnatal care, or for cannot be maintained. a chronic condition)

Community Community outreach programs (e.g., bed net distribution)

No Health workers and Health facility Providing any patient care Medical mask use documented caregivers (including primary, according to SARS-CoV-2 secondary, tertiary care standard and transmission levels, outpatient care, transmission-based

and long-term care precautions facilities)

Community Community outreach programs

Any Health workers Health care facility Performing an AGP on a Respirator (N95 or transmission (including primary, suspected or confirmed COVID- N99 or FFP2 or scenario secondary, tertiary care 19 patient or providing care in a FFP3)

levels, outpatient care, setting where AGPs are in place and long-term care for COVID-19 patients facilities), in settings where aerosol generating procedures (AGP) are performed

• This table refers only to the use of medical masks and respirators. The use of medical masks and respirators may need to be combined with other personal protective equipment and other measures as appropriate, and always with hand hygiene.

Guidance on mask use in community settings

Evidence on the protective effect of mask use in community settings

At present there is only limited and inconsistent scientific evidence to support the effectiveness of masking of healthy people in the community to prevent infection with respiratory viruses, including SARS-CoV-2 (75). A large randomized community-based trial in which 4862 healthy participants were divided into a group wearing medical/surgical masks and a control group found no difference in infection with SARS-CoV-2 (76). A recent systematic review found nine trials ( of which eight were cluster-randomized controlled trials in which clusters of people, versus individuals, were randomized) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness. Two trials were with healthcare workers and seven in the community. The review concluded that wearing a mask may make little or no difference to the prevention of influenza-like illness (ILi) (RR 0.99, 95%CI 0.82 to 1.18) or laboratory confirmed illness (LCI) (RR 0.91, 95%CI 0.66-1.26) (44); the certainty of the evidence was low for ILi, moderate for LCI.

By contrast, a small retrospective cohort study from Beijing found that mask use by entire families before the first family member developed COVID-19 symptoms was 79% effective in reducing transmission (OR 0.21, 0.06-0.79) (77). A casecontrol study from Thailand found that wearing a medical or non-medical mask all the time during contact with a COVID-19 patient was associated with a 77% lower risk of infection (aOR 0.23; 95% CI 0.09-0.60) (78). Several small observational studies with epidemiological data have reported an association between mask use by an infected person and prevention of onward transmission of SARSCo V-2 infection in public settings. (8, 79-81 ).

A number of studies, some peer reviewed (82-86) but most published as pre-prints (87-104), reported a decline in the COVID-19 cases associated with face mask usage by the public, using country- or region-level data. One study reported an association between community mask wearing policy adoption and increased movement (less time at home, increased visits to commercial locations) (105). These studies differed in setting, data sources and statistical methods and have important limitations to consider ( 106), notably the lack of information about actual exposure risk among individuals, adherence to mask wearing and the enforcement of other preventive measures ( I 07, 108).

Studies of influenza, influenza-like illness and human coronaviruses (not including COVID-19) provide evidence that the use of a medical mask can prevent the spread of infectious droplets from a symptomatic infected person to someone else and potential contamination of the environment by these droplets (75). There is limited evidence that wearing a medical mask may be beneficial for preventing transmission between healthy individuals sharing households with a sick person or among attendees of mass gatherings (44, 109-114).

3 For adequate ventilation refer to regional or national institutions or h~ting, refrigerating and air-conditioning societies enacting ventilation requirements. Ifnot available or applicable, a recommended ventilation rate of IO Vs/person should be met (except healthcare facilities which have specific requirements). For more information consult "Coronavirus (COVID-19) response

A meta-analysis of observational studies on infections due to betacoronaviruses, with the intrinsic biases of observational data, showed that the use of either disposable medical masks or reusable 12-16-layer cotton masks was associated with protection of healthy individuals within households and among contacts of cases ( 46). This could be considered to be indirect evidence for the use of masks (medical or other) by healthy individuals in the wider community; however, these studies suggest that such individuals would need to be in close proximity to an infected person in a household or at a mass gathering where physical distancing cannot be achieved to become infected with the virus. Results from cluster randomized controlled trials on the use of masks among young adults living in university residences in the United States of America indicate that face masks may reduce the rate of influenza-like illness but showed no impact on risk of laboratory-confirmed influenza ( 115, 116).

Guidance

The WHO COVID-19 IPC GOG considered all available evidence on the use of masks by the general public including effectiveness, level of certainty and other potential benefits and harms, with respect to transmission scenarios, indoor versus outdoor settings, physical distancing and ventilation. Despite the limited evidence of protective efficacy of mask wearing in community settings, in addition to all other recommended preventive measures, the GOG advised mask wearing in the following settings:

1. In areas with known or suspected community or cluster transmission of SARS-CoV-2, WHO advises mask use by the public in the following situations (see Table 2):

Indoor settings: - in public indoor settings where ventilation is known to be

poor regardless of physical distancing: limited or no opening of windows and doors for natural ventilation; ventilation system is not properly functioning or maintained; or cannot be assessed;

- in public indoor settings that have adequate3 ventilation if physical distancing of at least 1 metre cannot be maintained;

- in household indoor settings: when there is a visitor who is not a household member and ventilation is known to be poor, with limited opening of windows and doors for natural ventilation, or the ventilation system cannot be assessed or is not properly functioning, regardless of whether physical distancing of at least I metre can be maintained;

- in household indoor settings that have adequate ventilation if physical distancing of at least 1 metre cannot be maintained.

resources from ASHRAE and others,, https://www.ashrae.org/technical-resources/resources

Table 2. Mask use in community settings depending on transmission scenario, setting, target population, purpose and type*

Transmission scenario

Situations/settings (where) Target Population (who)

Known or suspected Indoor settings, where community or ventilation is known to be cluster transmission poor or cannot be assessed or of SAR.S-Co V-2 the ventilation system is not

General population in public* settings such as shops, shared workplaces, schools, churches, restaurants, gyms, etc. or in enclosed settings such as public transportation. properly maintained,

regardless of whether

physical distancing of at least For households, in indoor settings, when _1 _m_e_t_er_c_an_b_e_m_a_in_t_a_in_e_d _ ___. there is a visitor who is not a member of

Indoor settings that have the household adequate 4 ventilation if physical distancing of at least 1 metre cannot be maintained

Outdoor settings where General population in settings such as physical distancing cannot be crowded open-air markets, lining up maintained outside a building, during

demonstrations, etc.

Purpose of mask use

(why)

Potential benefit for source control

Settings where physical Individuals/people with higher risk of Protection

Known or suspected sporadic transmission, or no documented SARSCo V-2 transmission

distancing cannot be severe complications from COVID-19: maintained, and the individual • People aged ~60 years is at increased risk of infection and/or negative outcomes

Risk-based approach

• People with underlying comorbidities, such as cardiovascular disease or diabetes mellitus, chronic lung disease, cancer, cerebrovascular disease, immunosuppression, obesity, asthma

General population Potential benefit for source control and/or protection

Any transmission Any setting in the community Anyone suspected or confirmed of Source scenario having COVID-19, regardless of control

whether they have symptoms or not, or anyone awaiting viral test results, when in the presence of others

• Public indoor setting includes any indoor setting outside of the household

Mask type (which one)

Fabric mask

Medical mask

Depends on purpose (see details in the guidance content)

Medical mask

4 For adequate ventilation refer to regional or national institutions or heating, refrigerating and air-conditioning societies enacting ventilation requirements. Ifnot available or applicable, a recommended ventilation rate of 101/s/person should be met (except healthcare facilities which have specific requirements).). For more infonnation consult "Coronavirus (COVID-19) response resources from ASHRAE and others" https://www.ashrae.org/technical-resources/resources

In outdoor settings: - where physical distancing of at least 1 metre cannot be

maintained;

- individuals/people with higher risk of severe complications from COVID-19 (individuals ::: 60 years old and those with underlying conditions such as cardiovascular disease or diabetes mellitus, chronic lung disease, cancer, cerebrovascular disease or immunosuppression) should wear medical masks in any setting where physical distance cannot be maintained.

2. In areas with known or suspected sporadic transmission or no documented transmission, as in all transmission scenarios, WHO continues to advise that decision makers should apply a risk-based approach focusing on the following criteria when considering the use of masks for the public: • Purpose of mask use. Is the intention source control

(preventing an infected person from transmitting the virus to others) or protection (preventing a healthy wearer from the infection)?

• Risk of exposure to SARS-Co V-2. Based on the epidemiology and intensity of transmission in the population, is there transmission and limited or no capacity to implement other containment measmes such as contact tracing, ability to cany out testing and isolate and care for suspected and confinned cases? Is there risk to individuals working in close contact with the public ( e.g., social workers, personal support workers, teachers, cashiers)?

• Vulnerability of the mask wearer/population. Is the mask wearer at risk of severe complications from COVID-19? Medical masks should be used by older people (2: 60 years old), immunocompromised patients and people with comorbidities, such as cardiovascular disease or diabetes mellitus, chronic lung disease, cancer and cerebrovascular disease ( 117).

• Setting in which the population lives. Is there high population density (such as in refugee camps, camp-like settings, and among people living in cramped conditions) and settings where individuals are unable to keep a physical distance of at least 1 metre (for example, on public transportation)?

• Feasibility. Are masks available at an affordable cost? Do people have access to clean water to wash fabric masks, and can the targeted population tolerate possible adverse effects of wearing a mask?

• Type of mask. Does the use of medical masks in the community divert this critical resource from the health workers and others who need them the most? In settings where medical masks are in short supply, stocks should be prioritized for health workers and at-risk individuals.

The decision of governments and local jurisdictions whether to recommend or make mandatory the use of masks should be based on the above assessment as well as the local context, culture, availability of masks and resources required.

3. In any transmission scenario: • Persons with any symptoms suggestive of COVID-19

should wear a medical mask and ( S) additionally: - self-isolate and seek medical advice as soon as they

start to feel unwell with potential symptoms of COVID-19, even if symptoms are mild);

- follow instructions on how to put on, take off, and dispose of medical masks and perform hand hygiene (118);

- follow all additional measures, in particular respiratory hygiene, frequent hand hygiene and maintaining physical distance of at least I metre from other persons ( 46). If a medical mask is not available for individuals with suspected or confirmed COVID-19, a fabric mask meeting the specifications in the Annex of this document should be worn by patients as a source control measure, pending access to a medical mask. The use of a nonmedical mask can minimize the projection of respiratory droplets from the user (119, 120).

- Asymptomatic persons who test positive for SARSCo V-2, should wear a medical mask when with others for a period of 10 days after testing positive.

Potential benefits/harms

The potential advantages of mask use by healthy people in the general public include: • reduced spread of respiratory droplets containing

infectious viral particles, including from infected persons before they develop symptoms ( 121 );

• reduced potential for stigmatization and greater of acceptance of mask wearing, whether to prevent infecting others or by people caring for COVID-19 patients in non-clinical settings (122);

• making people feel they can play a role in contributing to stopping spread of the virus;

• encouraging concurrent transmission prevention behaviours such as hand hygiene and not touching the eyes, nose and mouth (123-125);

• preventing transmission of other respiratory illnesses like tuberculosis and influenza and reducing the burden of those diseases during the pandemic (126).

The potential disadvantages of mask use by healthy people in the general public include: • headache and/or breathing difficulties, depending on

type of mask used (55); • development of facial skin lesions, irritant dermatitis or

worsening acne, when used frequently for long hours (58, 59, 127);

• difficulty with communicating clearly, especially for persons who are deaf or have poor hearing or use lip reading ( 128, 129);

• discomfort (44, 55, 59) • a false sense of security leading to potentially lower

adherence to other critical preventive measures such as physical distancing and hand hygiene ( 105);

• poor compliance with mask wearing, in particular by young children (111, 130-132);

• waste management issues; improper mask disposal leading to increased litter in public places and environmental hazards (133);

• disadvantages for or difficulty wearing masks, especially for children, developmentally challenged persons, those with mental illness, persons with cognitive impairment, those with asthma or chronic respiratory or breathing problems, those who have had facial trauma or recent oral maxillofacial surgery and those living in hot and humid environments (55, 130).

Considerations for implementation

When implementing mask policies for the public, decisionmakers should: • clearly communicate the purpose of wearing a mask,

including when, where, how and what type of mask should be worn; explain what wearing a mask may achieve and what it will not achieve; and communicate clearly that this is one part of a package of measures along with hand hygiene, physical distancing, respiratory etiquette, adequate ventilation in indoor settings and other measures that are all necessary and all reinforce each other;

• inform/train people on when and how to use masks appropriately and safely (see mask management and maintenance sections);

• consider the feasibility of use, supply/access issues ( cleaning, storage), waste management, sustainability, social and psychological acceptance ( of both wearing and not wearing different types of masks in different contexts);

• continue gathering scientific data and evidence on the effectiveness of mask use (including different types of masks) in non-health care settings;

• evaluate the impact (positive, neutral or negative) of using masks in the general population (including behavioural and social sciences) through good quality research.

Mask use during physical activity

Evidence

There are limited studies on the benefits and harms of wearing medical masks, respirators and non-medical masks while exercising. Several studies have demonstrated statistically significant deleterious effects on various cardiopulmonary physiologic parameters during mild to moderate exercise in healthy subjects and in those with underlying respiratory diseases ( 134-140). The most significant impacts have been consistently associated with the use of respirators and in persons with underlying obstructive airway pulmonary diseases such as asthma and chronic obstructive pulmonary disease (COPD), especially when the condition is moderate to severe (136). Facial microclimate changes with increased temperature, humidity and perceptions of dyspnoea were also reported in some studies on the use of masks during exercise (134, 141). A recent review found negligeable evidence of negative effects of mask use during exercise but noted concern for individuals with severe cardiopulmonary disease (142).

Guidance

WHO advises that people should not wear masks during vigorous intensity physical activity (143) because masks may reduce the ability to breathe comfortably. The most important preventive measure is to maintain physical distancing of at least 1 meter and ensure good ventilation when exercising.

If the activity takes place indoors, adequate ventilation should be ensured at all times through natural ventilation or a properly functioning or maintained ventilation system ( 144 ). Particular attention should be paid to cleaning and disinfection of the environment, especially high-touch surfaces. If all the above measures cannot be ensured, consider temporary closure of public indoor exercise facilities ( e.g., gyms).

Face shields for the general public

At present, face shields are considered to provide a level of eye protection only and should not be considered as an equivalent to masks with respect to respiratory droplet protection and/or source control. Current laboratory testing standards only assess face shields for their ability to provide eye protection from chemical splashes (145).

In the context of non-availability or difficulties wearing a non-medical mask (in persons with cognitive, respiratory or hearing impairments, for example), face shields may be considered as an alternative, noting that they are inferior to masks with respect to droplet transmission and prevention. If face shields are to be used, ensure proper design to cover the sides of the face and below the chin.

Medical masks for the care of COVID-19 patients at home

WHO provides guidance on how to care for patients with confirmed and suspected COVID-19 at home when care in a health facility or other residential setting is not possible (5).

Persons with suspected COVID-19 or mild COVID-19 symptoms should wear a medical mask as much as possible, especially when there is no alternative to being in the same room with other people. The mask should be changed at least once daily. Persons who cannot tolerate a medical mask should rigorously apply respiratory hygiene (i.e., cover mouth and nose with a disposable paper tissue when coughing or sneezing and dispose of it immediately after use or use a bent elbow procedure and then perform hand hygiene). Caregivers of or those sharing living space with people with suspected COVID-19 or with mild COVID-19 symptoms should wear a medical mask when in the same room as the affected person.

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Acknowledgments

This document was developed based on advice by the Strategic and Technical Advisory Grou~ for Infecti~us Hazards (STAG-IH), and in consultation with the followmg members of:

1) The WHO Health Emergencies Programme (WHE) A?hoc COVID-19 IPC Guidance Development Group (m alphabetical order):

Jameela Alsalman, Ministry of Health, Bahrain; ~ucha Apisamthanarak, Thammsat University Hospital, Thailand; Baba Aye, Public Services International~ France; Gregory Built, UNICEF, United States of Amenca (USA); Roger Chou, Oregon Health Science University, USA; May Chu,

Colorado School of Public Health, USA; John Conly, Alberta Health Services, Canada; Barry Cookson, University College London, United Kingdom (U.K); Nizam Damani, Southern Health & Social Care Trust, United Kingdom; Dale Fisher, GOARN, Singapore; Joost Hopman, Radboud University Medical Center, The Netherlands; Mushtuq Husain, Institute of Epidemiology, Disease Control & Research, Bangladesh; Kushlani Jayatilleke, Sri Jayewardenapura General Hospital, Sri Lanka; Seto Wing Jong, School of Public Health, Hong Kong SAR, China; Souha Kanj, American University of Beirut Medical Center, Lebanon; Daniele Lantagne, Tufts University, USA; Fernanda Lessa, Centers for Disease Control and Prevention, USA; Anna Levin, University of Sao Paulo, Brazil; Ling Moi Lin, Sing Health, Singapore; Caline Mattar, World Health Professions Alliance, USA; MaryLouise Mclaws, University of New South Wales, Australia; Geeta Mehta, Journal of Patient Safety and Infection Control, India; Shaheen Mehtar, Infection Control Africa Network, South Africa; Ziad Memish, Ministry of Health, Saudi Arabia; Babacar Ndoye, Infection Control Africa Network, Senegal; Fernando Otaiza, Ministry of Health, Chile; Diamantis Plachouras, European Centre for Disease Prevention and Control, Sweden; Maria Clara Padoveze, School of Nursing, University of Sao Paulo, Brazil; Mathias Pletz, Jena University, Germany; Marina Salvadori, Public Health Agency of Canada, Canada; Mitchell Schwaber, Ministry of Health, Israel; Nandini Shetty, Public Health England, United Kingdom; Mark Sobsey, University ofNorth Carolina, USA; Paul Ananth Tambyah, National University Hospital, Singapore; Andreas Voss, Canisus-Wilhelmina Ziekenhuis, The Netherlands; Walter Zingg, University of Geneva Hospitals, Switzerland;

2) The WHO Technical Advisory Group of Experts on Personal Protective Equipment (TAG PPE):

Faisal Al Shehri, Saudi Food and Drug Authority, Saudi Arabi; Selcen Ayse, Istanbul University-Cerrahpasa, Turkey; Razan Asally, Saudi Food and Drug Authority, Saudi Arabi; Kelly Catlin, Clinton Health Access Initiative; Patricia Ching, WHO Collaborating Center, The University of Hong Kong, China; Mark Croes, Centexbel, Spring Gombe, United Nations; Emilio Homsey, UK Public Health Rapid Support Team, U.K.; Selcen Kilinc-Balci, United States Centers for

Disease Control and Prevention (CDC), USA; Melissa Leavitt, Clinton Health Access Initiative; John McGhie, International Medical Corps; Claudio Meirovich, Meirovich Consulting; Mike Paddock, UNDP, Trish Perl, University of Texas Southwestern Medical Center, USA; Alain Prat, Global Fund, Ana Maria Rule, Johns Hopkins Bloomberg School of Public Health, U .S.A; Jitendar Sharma, Andra Pradesh MedTEch Zone, India; Alison Syrett, SIGMA, Reiner Voelksen, VOELKSEN Regulatory Affairs, Nasri Yussuf, IPC Kenya.

3) External IPC peer review group:

Paul Hunter, University of East Anglia, U.K; Direk Limmathurotsakul, Mahidol University, Thailand; Mark Loeb, Department of Pathology and Molecular Medicine, McMaster University, Canada; Kalisavar Marimuthu, National Centre for Infectious Diseases, Singapore; Yong Loo Lin School of Medicine, National University of Singapore; Nandi Siegfried, South African Medical Research Council, South Africa.

4) UNICEF observers: Nagwa Hasanin, Sarah Karmin, Raoul Kamadjeu, Jerome Pfaffinann,

WHO Secretariat:

Benedetta Allegranzi, Gertrude Avortri, Mekdim Ayana, Hanan Balkhy, April Baller, Elizabeth Barrera-Cancedda, Anjana Bhushan, Whitney Blanco, Sylvie Briand, Alessandro Cassini, Giorgio Cometto, Ana Paula Coutinho Rehse, Carmem Da Silva, Nino Dal Dayanguirang, Sophie Harriet Dennis, Sergey Eremin, Luca Fontana, Dennis Falzon, Nathan Ford, Nina Gobat, Jonas Gonseth-Garcia, Rebeca Grant, Tom Grein, Ivan Ivanov, Landry Kabego, Catherine Kane, Pierre Claver Kariyo, Ying Ling Lin, Omelia Lincetto, Abdi Mahamud, Madison Moon, Takeshi Nishijima, Kevin Babila Ousman, Pillar Ramon-Pardo, Paul Rogers, Nahoko Shindo, Alice Simniceanu, Valeska Stempliuk, Maha Talaat Ismail, Joao Paulo Toledo, Anthony Twywan, Maria Van Kerkhove, Adriana Velazquez, Vicky Willet, Masahiro Zakoji, Bassim Zayed.

WHO continues to monitor the situation closely for any changes that may affect this interim guidance. Should any factors change, WHO will issue a further update. Otherwise, this interim guidance document will expire I year after the date of publication.

Annex: Updated guidance on non-medical (fabric) masks

Background

A non-medical mask, also called fabric mask, community mask or face covering, is neither a medical device nor personal protective equipment. Non-medical masks are aimed at the general population, primarily for protecting others from exhaled virus-containing droplets emitted by the mask wearer. They are not regulated by local health authorities or occupational health associations, nor is it required for manufacturers to comply with guidelines established by standards organizations. Non-medical masks may be homemade or manufactured. The essential performance parameters include good breathability, filtration of droplets originating from the wearer, and a snug fit covering the nose and mouth. Exhalation valves on masks are discouraged as they bypass the filtration function of the mask.

Non-medical masks are made from a variety of woven and nonwoven fabrics, such as woven cotton, cotton/synthetic blends, polyesters and breathable spunbond polypropylene, for example. They may be made of different combinations of fabrics, layering sequences and available in diverse shapes. Currently, more is known about common household fabrics and combinations to make non-medical masks with target filtration efficiency and breathability (119, 146-150). Few of these fabrics and combinations have been systematically evaluated and there is no single design, choice of material, layering or shape among available non-medical masks that are considered optimal. While studies have focussed on single fabrics and combinations, few have looked at the shape and universal fit to the wearer. The unlimited combination of available fabrics and materials results in variable filtration and breathability.

In the context of the global shortage of medical masks and PPE, encouraging the public to create their own fabric masks may promote individual enterprise and community integration. Moreover, the production of non-medical masks may offer a source of income for those able to manufacture masks within their communities. Fabric masks can also be a form of cultural expression, encouraging public acceptance of protection measures in general. The safe re-use of fabric masks will also reduce costs and waste and contribute to sustainability ( 151-156).

This Annex is destined intended for two types of readers: homemade mask makers and factory-made masks manufacturers. Decision makers and managers (national/subnational level) advising on a type of non-medical mask are also the focus of this guidance and should take into consideration the following features of non-medical masks: breathability, filtration efficiency (FE), or filtration, number and combination of fabric layers material used, shape, coating and maintenance.

Evidence on the effectiveness of non-medical (fabric) masks

A number of reviews have been identified on the effectiveness of non-medical masks ( 151-156). One systematic review ( 155) identified 12 studies and evaluated study quality. Ten were laboratory studies (157-166), and two reports were from a single randomized trial (72, 167). The majority of studies were conducted before COVID-19 emerged or used laboratory generated particles to assess filtration efficacy. Overall, the reviews concluded that

cloth face masks have limited efficacy in combating viral infection transmission.

Homemade non-medical masks

Homemade non-medical masks made of household fabrics (e.g., cotton, cotton blends and polyesters) should ideally have a three-layer structure, with each layer providing a function (see Figure I) ( 168). It should include:

1. an innermost layer (that will be in contact with the face) of a hydrophilic material ( e.g., cotton or cotton blends of terry cloth towel, quilting cotton and flannel) that is nonirritating against the skin and can contain droplets ( 148)

2. a middle hydrophobic layer of synthetic breathable nonwoven material (spunbond polypropylene, polyester and polyaramid), which may enhance filtration, prevent permeation of droplets or retain droplets ( 148, 150)

3. an outermost layer made of hydrophobic material (e.g. spunbond polypropylene, polyester or their blends), which may limit external contamination from penetrating through the layers to the wearer's nose and mouth and maintains and prevents water accumulation from blocking the pores of the fabric ( 148).

Although a minimum of three layers is recommended for nonmedical masks for the most common fabric used, single, double or other layer combinations of advanced materials may be used if they meet performance requirements. It is important to note that with more tightly woven materials, breathability may be reduced as the number of layers increases. A quick check may be performed by attempting to breathe, through the mouth, through the multiple layers.

Inner

• Hydrophilic •Cotton or cotton blend

Outer

• Hydrophobic •Polyester

Figure I. Non-medical mask construction using breathable fabrics such as cotton, cotton blends, polyesters, nylon and polypropylene spunbond that are breathable may impart adequate filtration performance when layered. Single- or double-layer combinations of advanced materials may be used if they meet performance requirements (72).

Assumptions regarding homemade masks are that individual makers only have access to common household fabrics and do not have access to test equipment to confirm target performance (filtration and breathability). Figure 1 illustrates a multi-layer mask construction with examples of fabric options. Very porous materials, such as gauze, even with multiple layers, may provide very low filtration efficiency ( 14 7). Higher thread count fabrics offer improved filtration performance ( 169). Coffee filters, vacuum bags and materials not meant for clothing should be avoided as they may contain injurious content when breathed in. Microporous films such as Gore-Tex are not recommended ( 170).

Factory-made non-medical masks: general considerations for manufacturers

The non-medical mask, including all components and packaging, must be non-hazardous, non-toxic and childfriendly (no exposed sharp edges, protruding hardware or rough materials). Factory-made non-medical masks must be made using a process that is certified to a quality management system ( e.g., ISO 9001 ). Social accountability standards ( e.g., SAi SA8000) for multiple aspects of fair labour practices, health and safety of the work force and adherence to UNICEF's Children's Rights and Business Principles are strongly encouraged.

Standards organizations' performance criteria

Manufacturers producing masks with consistent standardized performance can adhere to published, freely available guidance from several organizations including those from: the French Standardization Association (AFNOR Group), The European Committee for Standardization (CEN), Swiss National COVID-19 Task Force, the American Association of Textile Chemists and Colorists (AA TCC), the South Korean Ministry of Food and Drug Safety (MFDS), the Italian Standardization Body (UNI) and the Government of Bangladesh.

Essential parameters

The essential parameters presented in this section are the synthesis of the abovementioned regional and national guidance. They include filtration, breathability and fit. Good performance is achieved when the three essential parameters are optimized at the preferred threshold (Figure 2).

Figure 2. Illustration of the three essential parameters of fdtration, breatbability and fit.

The summary of the three essential parameters can be found in Table 1 and the additional performance considerations in Table 2. The minimum threshold is the minimum acceptable parameter, while the preferred threshold is the optimum.

Filtration and breathability

Filtration depends on the filtration efficiency (in%), the type of challenge particle ( oils, solids, droplets containing bacteria) and the particle size (see Table 1 ). Depending on the fabrics used, filtration and breathability can complement or work against one another. The selection of material for droplet filtration (barrier) is as important as breathability. Filtration is dependent on the tightness of the weave, fibre or thread diameter. Non-woven materials used for disposable masks are manufactured using processes to create polymer fibres that are thinner than natural fibres such as cotton and that are held together by partial melting.

Breathability is the difference in pressure across the mask and is typically reported in millibars (mbar) or Pascals (Pa) or, normalized to the cm2 in mbar/cm2 or Pa/cm2• Acceptable breathability of a medical mask should be below 49 Pa/cm2•

For non-medical masks, an acceptable pressure difference, over the whole mask, should be below 60 Pa/cm2, with lower values indicating better breathability.

Non-medical fabric masks consisting of two layers of polypropylene spunbond and two layers of cotton have been shown to meet the minimum requirements for droplet filtration and breathability of the CEN CWA 17553 guidance. It is preferable not to select elastic material to make masks as the mask material may be stretched over the face, resulting in increased pore size and lower filtration through multiple usage. Additionally, elastic fabrics are sensitive to washing at high temperatures thus may degrade over time.

Coating the fabric with compounds like wax may increase the barrier and render the mask fluid resistant; however, such coatings may inadvertently completely block the pores and make the mask difficult to breathe through. In addition to decreased breathability unfiltered air may more likely escape the sides of the mask on exhalation. Coating is therefore not recommended.

Valves that let unfiltered air escape the mask are discouraged and are an inappropriate feature for masks used for the purpose of preventing transmission.

Table 1. Essential parameters (minimum and preferred thresholds) for manufactured non-medical mask

Essential Minimum threshold Preferred threshold Parameters

1. Filtration* 1.1. filtration

70% @ 3 micron > 70%, without compromising breathability efficiency

1.2. Challenge Solid: sodium chloride (NaCl), Talcum Based on availability particle powder, Holi powder, dolomite, Polystyrene

Latex spheres

Liquid: DEHS Di-Ethyl-Hexyl-Sebacat, paraffin oil

1.3. Particle size Choose either sizes: Range of particle sizes

3 um. 1 um. or smaller

2. Breathability

2.1. Breathing S60 Pa/cm2 Adult: S 40 Pa/cm2

resistance** Paediatric: < 20 Pa/cm2

2.2 Exhalation Not recommended NIA valves

3. Fit

3.1. Coverage Full coverage of nose and mouth, consistent, Same as current requirements snug perimeter fit at the nose bridge, cheeks, chin and lateral sides of the face; adequate surface area to minimize breathing resistance and minimize side leakruze

3.2 Face seal Not currently required Seal as good as FFR (respirator):

Fit factor of 100 for N95

Maximum Total Inward Leakage of 25% (FFPl requirement)

3.2. Sizing Adult and child Should cover from the bridge of the nose to below the chin and cheeks on either side of the mouth

Sizing for adults and children (3-5, 6-9, 10-12, >12)

3.3Strap stren2th >44.SN

• Smaller particle may result in lower filtration. •• High resistance can cause bypass of the mask. Unfiltered air will leak out the sides or around the nose if that is the easier path.

Fit: shape and sizing

Fit is the third essential parameter, and takes into consideration coverage, seal, sizing, and strap strength. Fit of masks currently is not defined by any standard except for the anthropometric considerations of facial dimensions (ISO/TS 16976-2) or simplified to height mask (South Korean standard for KF-AD). It is important to ensure that the mask can be held in place comfortably with as little adjustment of the elastic bands or ties as possible.

Mask shapes typically include flat-fold or duckbill and are designed to fit closely over the nose, cheeks and chin of the wearer. Snug fitting designs are suggested as they limit leaks of unfiltered air escaping from the mask ( 148). Ideally the mask should not have contact with the lips, unless hydrophobic fabrics are used in at least one layer of the mask ( 148). Leaks where unfiltered air moves in and out of the mask may be attributed to the size and shape of the mask (171).

Additional considerations

Optional parameters to consider in addition to the essential performance parameters include if reusable, biodegradability for disposal masks, antimicrobial performance where applicable and chemical safety (see Table 2).

Non-medical masks intended to be reusable should include instructions for washing and must be washed a minimum of five cycles, implying initial performance is maintained after each wash cycle.

Advanced fabrics may be biodegradable or compostable at the end of service life, according to a recognized standard process (e.g., UNI EN 13432, UNI EN 14995 and UNI/ PdR 79).

Manufacturers sometimes claim their NM masks have antimicrobial performance. Antimicrobial performance may be due to coatings or additives to the fabric fibres. Treated fabrics must not come into direct contact with mucous membranes; the innermost fabric should not be treated with

antimicrobial additives, only the outermost layer. In addition, antimicrobial fabric standards (e.g., ISO 18184, ISO 20743, AATCC TMIO0, AATCC 100) are generally slow acting. The inhibition on microbial growth may take full effect after 2- or 24-hour contact time depending on the standard. The standards have generally been used for athletic apparel and substantiate claims of odour control performance. These standards are not appropriate for non-medical cloth masks and may provide a false sense of protection from infectious agents. If claims are maid, manufacturers should specify which standard supports antimicrobial performance, the challenge organism and the contact time.

Volatile additives are discouraged as these may pose a health risk when inhaled repeatedly during wear. Certification according to organizations including OEKO-TEX (Europe) or SEK (Japan), and additives complying with REACH (Europe) or the Environmental Protection Agency (EPA, United States of America) indicate that textile additives are safe and added at safe levels.

Table 2. Additional parameters for manufactured nonmedical masks

Additional parameters Minimum thresholds

If reusable, number of wash 5 cycles cycles

Disposal Reusable

If biodegradable (CFC-BIO), according to UNI EN 13432. UNI EN 14995

Antimicrobial (bacteria, ISO 18184 (virus) virus, fungus) performance

ISO 20743 (bacteria)

ISO 13629 (fungus)

AA TCC TM 100 (bacteria)

Chemical safety Comply with REACH regulation, including inhalation safety

© World Health Organization 2020. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO licence.

WHO reference number: WHO/2019-nCo V /IPC _Masks/2020.5

GLOBAL INFLUENZA PROGRAMME

Non-pharmaceutical public health measures for mitigating the risk and impact of epidemic and pandemic influenza

(mt?.~\ World Health ~~ti Organization ~


ISBN 978-92-4-151683-9 e World Health Organization 2019

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Iii NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


Cont nts Non-pharmaceutical public health measures for mitigating the risk and impact of epidemic and pandemic influenza

Acknowledgements

Abbreviations and acronyms

Glossary

Executive summary

1. Introduction

1.1. Introduction

1.1.1. Human influenza virus transmission

1.1.2. Public health importance

1.1.3. History of the guidelines for NPls in influenza pandemics

1.2. Scope, purpose and target audience

1.3. International Health Regulations

1.4. Pandemic influenza severity assessment framework

1.5. Guideline development process

1.5.1. Contributors to the process

1.5.2. Guideline development steps

2. Summary of recommendations

3. Communication for behavioural impact

4. Personal protective measures

4.1. Hand hygiene

4.2. Respiratory etiquette

4.3. Face masks

5. Environmental measures

5.1. Surface and object cleaning

5.2. Other environmental measures

5.2.1. Ultraviolet light

5.2.2. Increased ventilation

5.2.3. Modifying humidity

6. Social distancing measures

6.1. Contact tracing

6.2. Isolation of sick individuals

6.3. Quarantine of exposed individuals

6.4. School measures and closures

6.5. Workplace measures and closures

6.6. Avoiding crowding

7. Travel-related measures

7.1. Travel advice

7.2. Entry and exit screening

7.3. Internal travel restrictions

7.4. Border closure

References

WORLD HEALTH ORGANIZATION


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V

vi

5

5

5

5

9

9

10

10

10

10

11

13

19

20

20

24

26

28

28

31

31

33

35

37

37

40

44

48

53

57

79

60

62

64

67

70

Acknowledgements

This document is the product of collaboration between the World Health Organization (WHO) Global Influenza Programme and the WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, The University of Hong Kong.

The University of Hong Kong team was led by Benjamin Cowling, and included Jessica Wong, Sukhyun Ryu, Huizhi Gao, Eunice Shiu, Jingyi Xiao and Min Whui Fong. The team's contributions to carrying out the systematic reviews and developing this document are gratefully acknowledged.

WHO appreciates the contributions of the following experts before, during and after the Technical Consultation on Non-pharmaceutical Public Health Measures for Mitigating the Risk and Impact of Epidemic and Pandemic Influenza, which was held from 26 to 28 March 2019 in Hong Kong Special Administrative Region (SAR), China:

Allison Aiello, Alanoud Aljifri, Gemma Arellano, Gina Charos, Francisco de Paula Junior, Aleksander Deptula, Narangerel Dorj, Hind Ezzine, Rosaura Gutierrez-Vargas, Anand Krishnan, Vernon Lee, Svenn-Erik Mamelund, Punam Mangtani, Jeffrey McFarland, Armelle Viviane Ngomba, Jonathan Nguyen Van-Tam, Hitoshi Oshitani, Pasi Penttinen, Carrie Reed, Amra Uzicanin and Dayan Wang.

WHO also wishes to extend its appreciation to all who reviewed and commented on the earlier version of this document during the public comment period. The following individuals identified themselves but are not among the lists above:

Faruque Ahmed, Salah Al Awaidy, Kossi Badziklou, Aleksander Deptula, Luzhao Feng, Gary Lamont, Raina Nikiforova, Junxiong Vincent Pang, Trinehessevik Paulsen and Osvaldo Uez.

The following WHO staff and consultants are acknowledged for their contributions to the development and review of this document:

Abdinasir Abubakar, Isabelle Bergeri, Sylvie Briand, Caroline S. Brown, Amgad A. Elkholy, Julia Fitzner, Philip Gould, Aspen Hammond, Michala Hegermann-Lindencrone, Belinda L Herring, Masaya Kato, Jaya Lamichhane, Ann Moen, Sonja Olsen, Soatiana C. Rajatonirina, Gina Samaan, Magdi Samaan, Bhagawan D. Shrestha, Katelijn A.H. Vandemaele, Andrea Vicari, Wenqing Zhang and Weigong Zhou.

The technical editing of this document was performed by Hilary Cadman and the Cadman Editing Services team.

m NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


Abbreviations and acronyms

ACH air changes per hour

Cl confidence interval

COMBI communication for behavioural impact

GDP gross domestic product

GRADE Grading of Recommendations Assessment, Development and Evaluation

IHR International Health Regulations

NPI non-pharmaceutical intervention

OR odds ratio

PISA pandemic influenza severity assessment

RCT randomized controlled trial

RNA ribonucleic acid

RR rate ratio

SAR Special Administrative Region

USA United States of America

UV ultraviolet

WHO World Health Organization



Glossary

Contact tracing

Closure

Entry and exit screening

Isolation

Movement restridion

Identification and follow-up of persons who may have come into contact with an infected person.

Halting the operation of an institution or business.

Screening travellers for influenza virus infection at their arrival in and departure from border crossings, ports and airports.

Separation or confinement of a person who has or is suspected of having influenza virus infection, to prevent further infections.

Limitation on the movements of a person who has or is suspected of having influenza virus infection.

Personal protective measures Measures to reduce personal risk of infection, such as hand washing and face masks.

Quarantine

Respiratory etiquette

Symptomatic influenza

Travel Advice

Separation or restriction of the movement of persons who may be infected, based either on exposure to other infected people or on a history of travel to affected areas.

Basic reproductive number, a measure of transmissibility. This number represents the average number of people infected by one infectious case in a completely susceptible population.

Simple hygiene practices taken by people who are coughing or sneezing to prevent person-to-person transmission of respiratory infections.

Influenza virus infection causing an acute illness, most commonly with rapid onset of fever and other respiratory symptoms, although a proportion of illnesses are afebrile.

Health advice to travellers provided by national or international health agencies to help travellers understand the risks involved during the travel and take the necessary preventive measures or precautions to protect their health while travelling.



EXECUTIVE SUMMARY Introduction Influenza pandemics occur at unpredictable intervals, and cause considerable morbidity and mortality. Influenza virus is readily transmissible from person to person, mainly during close contact, and is challenging to control. In the early stage of influenza epidemics and pandemics, there may be delay in the availability of specific vaccines and limited supply of antiviral drugs. Non-pharmaceutical interventions (NPls) are the only set of pandemic countermeasures that are readily available at all times and in all countries. The potential impacts of NPls on an influenza epidemic or pandemic are to delay the introduction of the pandemic virus into a population; delay the height and peak of the epidemic if the epidemic has started; reduce transmission by personal protective or environmental measures; and reduce the total number of infections and hence the total number of severe cases.

Scope and purpose This document provides recommendations for the use of NPls in future influenza epidemics and pandemics based on existing guidance documents and the latest scientific literature. The specific recommendations are based on a systematic review of the evidence on the effectiveness of NPls, including personal protective measures, environmental measures, social distancing measures and travel-related measures. The information provided here will be useful for national authorities that are developing or updating their plans for mitigating the impact of influenza epidemics and pandemics.

Target audience This guideline is intended to support the development and updating of national plans for mitigating influenza epidemics and pandemics in community settings. The recommendations included in this guideline will also be of interest to individuals, organizations, institutions and local health authorities.

Methods The guideline development process included the following stages:

1. Identify a list of NPls that have the potential to contribute to pandemic mitigation for further review and evaluation.

2. Identify and evaluate existing systematic reviews of the NPls listed in Step 1, and perform new systematic reviews for each NPI if recently published reviews were not available.

3. Assess the body of evidence on the effectiveness of each of the NPls.

4. Determine the direction and strength of recommendations.

S. Draft the guideline document based on evidence and planning for strategy implementation.

The guideline development process included the formation of four main groups: a World Health Organization (WHO) guideline steering group, a systematic review team from the University of Hong Kong, a guideline development group and an external review group. The primary responsibilities of these four groups are, respectively, to oversee the process of the guideline development, to review the evidence base for each NPI, to formulate recommendations based on scientific evidence and other considerations, and to review the guidelines.



Available evidence The evidence base for this guideline included systematic reviews of 18 NPls, covering:

personal protective measures (e.g. hand hygiene, respiratory etiquette and face masks);

environmental measures (e.g. surface and object cleaning, and other environmental measures);

social distancing measures (e.g. contact tracing, isolation of sick individuals, quarantine of exposed individuals, school measures and closures, workplace measures and closures, and avoiding crowding); and

• travel-related measures (e.g. travel advice, entry and exit screening, internal travel restrictions and border closure).

The evidence base on the effectiveness of NPls in community settings is limited, and the overall quality of evidence was very low for most interventions. There have been a number of highquality randomized controlled trials (RCTs) demonstrating that personal protective measures such as hand hygiene and face masks have, at best, a small effect on influenza transmission, although higher compliance in a severe pandemic might improve effectiveness. However, there are few RCTs for other NPls, and much of the evidence base is from observational studies and computer simulations. School closures can reduce influenza transmission but would need to be carefully timed in order to achieve mitigation objectives. Travel-related measures are unlikely to be successful in most locations because current screening tools such as thermal scanners cannot identify pre-symptomatic infections and afebrile infections, and travel restrictions and travel bans are likely to have prohibitive economic consequences.

Recommendations Eighteen recommendations are provided in this guideline (Table 1 ). The recommendations take into account the quality of the supporting evidence, the strength of each recommendation and other considerations. In taking decisions on interventions, each WHO Member State and each local area will need to take into account the feasibility and acceptability of proposed interventions, in addition to their anticipated effectiveness and impact. This guideline provides an overview of relevant considerations.

D NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


Table 1. Recommendations on the use of NPls by severity level

SEVERITY

Any

Moderate

High

Extraordinary

Not recommended in any circumstances

PANDEMIC•

Hand hygiene Respiratory etiquette Face masks for symptomatic individuals Surface and object cleaning Increased ventilation Isolation of sick individuals Travel advice

As above, plus Avoiding crowding

As above, plus Face masks for public School measures and closures

As above, plus Workplace measures and closures Internal travel restrictions

UV light Modifying humidity Contact tracing Quarantine of exposed individuals Entry and exit screening Border closure

NPI: non-pharmaceutical intervention; UV: ultraviolet.

• A pandemic is defined as a global epidemic caused by a new influenza virus to which there is little or no pre-existing immunity in the human population ( 7).

EPIDEMIC

Hand hygiene Respiratory etiquette Face masks for symptomatic individuals Surface and object cleaning Increased ventilation Isolation of sick individuals Travel advice

As above, plus Avoiding crowding

As above, plus Face masks for public School measures and closures

As above, plus Workplace measures and closures

UV light Modifying humidity Contact tracing Quarantine of exposed individuals Entry and exit screening Internal travel restrictions Border closure

------------------------" WORLD HEALTH ORGANIZATION 1:.1


The most effective strategy to mitigate the impact of a pandemic is to reduce contacts between infected and uninfected persons, thereby reducing the spread of infection, the peak demand for hospital beds, and the total number of infections, hospitalizations and deaths. However, social distancing measures (e.g. contact tracing, isolation, quarantine, school and workplace measures and closures, and avoiding crowding) can be highly disruptive, and the cost of these measures must be weighed against their potential impact. Early assessments of the severity and likely impact of the pandemic strain will help public health authorities to determine the strength of intervention. In all influenza epidemics and pandemics, recommending that those who are ill isolate themselves at home should reduce transmission. Facilitating this should be a particular priority. In more severe pandemics, measures to increase social distancing in schools, workplaces and public areas would further reduce transmission.

Experimental studies suggest that hand hygiene can reduce virus on the hands. However, there is insufficient scientific evidence from RCTs to support the efficacy of hand hygiene alone to reduce influenza transmission in influenza epidemics and pandemics. Hand hygiene is an important intervention to reduce the risk of other common infectious diseases; therefore, it should be recommended at all times, regardless of the lack of efficacy against confirmed influenza reported in a number of RCTs. There is also a lack of evidence for the effectiveness of improved respiratory etiquette and the use of face masks in community settings during influenza epidemics and pandemics. Nevertheless, these NPls may be conditionally recommended for ill persons because of other considerations (e.g. the high cost of face masks), and they are generally feasible and acceptable. It is likely that these personal interventions could be effective if implemented in combination.

There is sufficient evidence on the lack of effectiveness of entry and exit screening to justify not recommending these measures in influenza pandemics and epidemics. There is weak evidence, mainly from simulation studies, that travel restrictions may only delay the introduction of infections for a short period, and this measure may affect mitigation programmes, be disruptive of supply chains or be unacceptable to communities for various reasons. There is no evidence on the effectiveness of travel advice; however, given the potential benefits. it is recommended that health authorities provide advice for travellers. Border closures may be considered only by small island nations in severe pandemics and epidemics, but must be weighed against potentially serious economic consequences.

This document will serve as a core component of WHO's influenza prevention and control programme in community settings. The successful implementation of this guideline depends on the inclusion of NPls as a robust strategic plan at national and local levels, as well as the appropriate application of its recommendations.



INTRODUCTION 1.1. Introduction

1.1.1. Human influenza virus transmission Influenza virus infection causes acute respiratory illness that is usually self-limiting but can be severe in some cases. Influenza virus infects the upper and lower respiratory tract, and spreads between people, mainly during close contact. The routes of transmission are often categorized into three specific modes - contact, aerosols and (large) respiratory droplets (2) - as outlined below.

Contact transmission Contact transmission is either direct or indirect. Transmission via direct physical contact can occur between an infected individual and a susceptible individual (e.g. through kissing or shaking hands). Transmission via indirect contact occurs through an intermediate object (e.g. touching contaminated surfaces or objects, and then touching nose or eyes) (2). Several studies have shown that influenza virus can survive for prolonged periods on certain types of surfaces, and can survive on hands for a short time (3).

Aerosol transmission Influenza virus can be detected in fine particle aerosols with an aerodynamic diameter of less than 5 µm, emitted by infected individuals in exhalations, coughs and sneezes (4). These tiny particles ( <5 µm) can reach the membrane surfaces of the upper respiratory tract and the epithelial cells of the lower respiratory tract (2). Although most aerosol transmission is likely to occur at close range because of dilution and inactivation over distance and time, these particles can remain suspended in the air for extended periods and may be responsible for higher rates of transmission, particularly in crowded areas (5).

Respiratory droplet transmission Droplet transmission is typically defined as transmission via droplets that follow a ballistic trajectory after emission and do not remain airborne; these particles have an aerodynamic diameter of 5-1 O µm (6). Virus-laden droplets are expelled into the environment by breathing, coughing and sneezing. These droplets generally travel short distances (1-2 m from the source) (5). Respiratory droplets are often thought to be the most common route of influenza transmission, although there is limited evidence to support this view.

Impacts of modes of transmission The various modes of transmission have implications for the effectiveness of personal protective measures against influenza transmission. Also, uncertainty over the specific role of contact and aerosol transmission has hindered the optimization of control strategies. In settings where multiple exposures occur, removing one mode of transmission (e.g. by intense hand hygiene) may not be sufficient to reduce overall transmission en. Isolating infected individuals - that is, keeping them away from others - is likely to reduce transmission by all modes.

1.1.2. Public health importance Influenza epidemics cause considerable impact each year, and influenza pandemics occur from time to time with potentially devastating health and economic effects. Because of the delay in the availability of specific vaccines and the limited stockpiles of antiviral drugs, non-pharmaceutical interventions (NPls) are often the only available intervention when a new pandemic influenza virus emerges and begins to spread (8). The implementation of community mitigation measures may help to reduce the impact of influenza epidemics and pandemics.

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Seasonal and pandemic influenza Seasonal epidemics of human influenza A and B virus infections occur in the winter months almost every year in temperate locations (9), leading to the commonly used term "seasonal" influenza. In tropical and subtropical locations, influenza A and B epidemics occur with weaker seasonality (10) or with year-round circulation (71).

Influenza viruses rapidly evolve to escape the immunity that results from prior infections, allowing continued circulation. The virus strains included in influenza vaccines are reviewed twice each year and are updated if necessary, to maintain higher effectiveness against prevalent circulating strains. Segments of the population at higher risk of severe outcomes from seasonal influenza infections include young children, older adults, adults with underlying medical conditions and pregnant women (9).

Influenza pandemics occur when a new influenza A virus emerges to which the population has little or no immunity. Before the 2009-2010 pandemic, it was believed that pandemics occurred when new influenza A subtypes emerged in the human population and replaced the previously circulating subtypes, as occurred in 1918-1919 with A(Hl Nl ), in 1957-1958 with A(H2N2) and in 1968-1969 with A(H3N2). When influenza A(H 1 N 1) re-emerged in 1977 after a 20-year absence ( 7 2), and co-circulated with A(H3N2) rather than replacing it, the re-emergence was not declared a pandemic. However, when the A(Hl N1 )pdm09 strain emerged in 2009, it was declared a pandemic after it spread globally, demonstrating that pandemic strains do not need to be a new subtype, but with shifted antigenicity from same sub type of seasonal influenza viruses circulating previously.( 7 3). Influenza pandemics are associated with higher attack rates because of the lack of population immunity, and they can have a substantial health impact. Some of the differences between seasonal and pandemic influenza are shown in Table 2 (9, 74-76).

Table 2. Comparison of lnterpandemic ("seasonar) influenza epidemics and pandemic influenza

INTERPANDEMIC INFLUENZA

Frequency Common: every year or almost every year

Viruses Involved Influenza A and 81

Antigenic Relatively small antigenic changes every characteristics year

Immunity Some population immunity from previous infections and from vaccination

Vaccines Specific vaccines available, with strains reviewed twice per year and updated as appropriate

Antivirals Antiviral drugs available in some locations, and used for the treatment of severe influenza or as clinically appropriate

b Influenza C virus Infections are sporadically detected, but this type has not been linked to large epidemics or major disease burden.

PANDEMIC INFLUENZA

Irregular: perhaps a few times each century

Influenza A

Major antigenic change in surface proteins

Low levels of population immunity

Specific vaccines may not be available for the first 6 months

Large stockpiles of antiviral drugs available in some

1 locations

i



Vulnerable population

lmpad

INTERPANDEMIC INFLUENZA

Groups with weaker immunity at highest risk of severe disease (e.g. young children, older adults, adults with underlying medical conditions and pregnant women)

Perhaps 500 000 respiratory deaths on average each year

PANDEMIC INFLUENZA

Attack rates may be highest in children and young adults; pregnant women are often at higher risk, as documented in several previous pandemics; the population segments at highest risk of severe influenza are unpredictable

Potentially millions of deaths

There were three major pandemics in the 20th century, commonly referred to as theuSpanish flu" in 1918-1919, the uAsian flu" in 1957-1958 and the "Hong Kong flu" in 1968-1969 (Table 3). The most serious of these was the pandemic caused by the A(Hl Nl) virus in 1918-1919, which resulted in 20-50 million deaths, and had a particularly notable impact on mortality in young adults (77). The A(H2N2) pandemic in 1957-1958 and the A(H3N2) pandemic in 1968-1969 each caused around 1 million deaths worldwide, with the greatest impact on mortality being in older adults (78).

The first influenza pandemic in the 21st century, which occurred in 2009-2010, was caused by a new strain of influenza A(Hl Nl) virus that was antigenically shifted from the seasonal influenza A(Hl Nl) strains circulating at the time, but antigenically similar to A(Hl Nl) strains that had circulated before 1950 ( 19). The virus is thought to have emerged in central America shortly before it was first detected in North America in April 2009, and subsequently spread rapidly to other parts of the world (20). Because of the similarity with older A(Hl Nl) viruses, older adults had some immunity, reducing the impact of A(Hl Nl )pdm09 in this age group (21). Globally, the pandemic was estimated to have caused 123 000-203 000 respiratory deaths in 2009 (22).

1918-1919°Spanlsh flu"

1957-1958°Aslan flu"

1968-1969"HongKongflu"

2009-2010 H1N1pdm09

H1N1 20-50 million deaths ( 7 7)

H2N2 1.1 million deaths (23)

H3N2 1 million deaths (23) -----------+----------------

H1N1 123 000-203 000 respiratory deaths (22)

Influenza pandemics typically occur in epidemic waves. For example, in 2009 the United States of America (USA) experienced a spring epidemic of A(H 1 N 1 )pdm09 that had a limited impact; the spring epidemic was followed by a much larger autumn epidemic that had a major health impact (24). Subsequent epidemics of A(Hl Nl )pdm09 have occurred every 2-3 years since 2009, with similar epidemiological characteristics to other seasonal influenza epidemics.

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The origin of pandemics A much greater range of influenza A subtypes of viruses circulates in animals, particularly in wild aquatic birds. Although human infections with avian influenza A subtypes are sporadic, there is a risk that these viruses will develop the capacity for effective transmission among humans, leading to the next pandemic. The emergence of highly pathogenic A(HSN 1) in 1997 raised the significant concern because of the severity of laboratory-confirmed human infections (25). More than 1000 laboratory-confirmed human infections with avian influenza A(H7N9) virus occurred in China in the period 2013-2018 (26), with no sustained human-to-human transmission (27). Several other avian influenza A subtypes (e.g. H9N2, H6N 1 and H7N7) have caused sporadic human infections (28). As demonstrated in 2009, influenza pandemics can also emerge from swine influenza viruses.

Non-pharmaceutical interventions NPls (also known as non-pharmacological interventions) include all measures or actions, other than the use of vaccines or medicines, that can be implemented to slow the spread of influenza in a population. In the early stage of influenza epidemics and pandemics, NPls are often the most accessible interventions, because of the time it takes to make specific vaccines available and because most locations do not have large stockpiles of antiviral drugs (8). Therefore, these mitigation measures will play a major role in reducing transmission in community settings. There are several objectives of NPls in an epidemic that is the first wave or subsequent wave of a pandemic or a seasonal influenza epidemic (29, 30).

Some NPls may be able to delay the start of an epidemic, which could be particularly important if the resulting delay is long enough to allow specific vaccines to be distributed and reduce the impact of the epidemic. Once an epidemic has started, NPls may also be used to delay the peak of the epidemic, again allowing time for vaccines to be distributed, or for health care providers to better prepare for a surge in cases.

By reducing transmission in the community, the epidemic may be spread out over a longer period, with a reduced epidemic peak. This can be particularly important if the health system has limited resources or capacity {e.g. in terms of hospital beds and ventilators). Also, overall morbidity and mortality can be reduced even if the total number of infections across the epidemic is not reduced.

Some interventions may aim to reduce the total number of infections, and therefore also reduce the total number of severe cases, hospitalizations and deaths.

Each of these consequences should contribute to reducing the overall impact of the epidemic or pandemic. NPls outside of health care settings usually focus on reducing transmission by personal protective or environmental measures {e.g. hand hygiene); reducing the spread in the community {e.g. isolating and treating patients, closing schools and cancelling mass gatherings); limiting the international spread (e.g. traveller screening); and improving risk communication with the public (31).

a NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


Fig. 1. Intended impact of NPls on an influenza epidemic or pandemic by reducing person-to-person transmission.

Spreacs cnses °""' a longor tlrne penod

Numoer of Clays aher first case

NPI: non-pharmaceutical intervention. Sources: US Centers for Disease Control and Prevention and European Centre for Disease Prevention and Control guidelines (29, 30).

1.1.3. History of the guidelines for NPls in influenza pandemics WHO published guidance on NPls in 2009 in response to the emergence of influenza A(Hl Nl)pdm09 (32-35). That guidance provided recommendations on the measures that can be used to reduce influenza transmission and mitigate the impact of epidemics and pandemics. The present update is the first since the 2009-2010 pandemic, and it takes into account both the experiences during that pandemic and the research on NPls done during the pandemic and since then. This guideline includes an updated review of all available evidence on the effectiveness of NPls in mitigating the risk and impact of influenza epidemics and pandemics, and will contribute to preparations for the next pandemic.

1.2. Scope, purpose and target audience

The overarching question posed in this guideline is "What are the effective non-pharmaceutical public health measures for mitigating the risk and impact of influenza epidemics and pandemics in community settings?"

Target audience This guideline aims to support the development and updating of national plans for mitigating influenza epidemics and pandemics in community settings. The advice will also be of interest to individuals, organizations, institutions and local health authorities.

Scope and purpose This guideline was developed from the existing guidance documents and the scientific literature. It examines evidence on the effectiveness of each of the NPls in community settings, and provides recommendations for dealing with future influenza epidemics and pandemics. The recommendations given here may help national or local health authorities to plan and make decisions for individuals or institutions outside of health care settings. The essential elements of these decisions are personal protective measures, environmental measures, social distancing measures, travel-related measures and risk communication. In addition, countries, localities, communities, schools, families and individuals can use this NPI guideline to determine the most appropriate measures to use, to mitigate the spread and minimize the adverse consequences of influenza epidemics and pandemics. Specific targets for the early implementation of NPls include slowing the transmission of infections in the community, spreading cases out over a longer period and reducing peak demand for medical services. Health system preparedness measures (e.g. ensuring adequate hospital beds, essential medicines and medical equipment) were outside the scope of this guideline. _______________________ ...

WORLD HEALTH ORGANIZATION a:J


The systematic review had some limitations, including publication bias and difficulties in addressing generalisability owing to the countries and regions where the studies selected were performed. Social and cultural differences between different countries and regions will influence the overall effectiveness of the NPI in different countries, and this needs to be emphasized, to moderate expectations. Implementation of NPls should be flexible depending on the local or national situation (or both).

1.3. International Health Regulations

The International Health Regulations (IHR) (2005) (36) entered into force in 2007 and have two overarching objectives (Article 2):

• to set out obligations and mechanisms for"a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks, and which avoid unnecessary interference with international traffic and trade"; and

• to strengthen the preparedness and capacities of countries so they can proactively detect, assess, report and address acute public health threats early.

The IHR (2005) seek to balance the sovereignty of individual States Parties with the common good of the international community, and take account of economic and social interests as well as the protection of health. Under the IHR (2005), governments are entitled to implement public health measures to protect the health of their populations during public health events respecting three golden rules, which are that such measures must be based on scientific principles, respect human rights, and not be more onerous or intrusive than reasonably available alternatives. When measures exceed these parameters, countries are obliged to provide the public health rationale to WHO within 48 hours of implementation, and to rescind the measures if they are deemed unjustified.

1.4. Pandemic influenza severity assessment framework

The pandemic influenza severity assessment (PISA) framework was introduced by WHO in 2017 (37). The severity of an influenza epidemic or pandemic is evaluated and monitored through three specific indicators: transmissibility (referring to incidence}, seriousness of disease, and impact on health care system and society. The severity is categorized into five levels: no activity or below seasonal threshold, low, moderate, high or extraordinary (37). The PISA framework is being tested and improved during seasonal influenza epidemics; the aim is to help public health authorities to monitor and assess the severity of influenza, and to inform appropriate decisions and recommendations on interventions. Of particular relevance to these guidelines on NPI use, the PISA evaluation of severity may inform the choice of which interventions to use and when to use them (e.g. some interventions may only be recommended in severe epidemics or pandemics).

1.5. Guideline development process

1.s.1. Contributors to the process This guidance document was developed with contributions from the systematic review team, guideline development and review groups and WHO Secretariat (the steering group} in accordance with the requirements of the WHO handbook for guideline development (38). The details of the contributors can be found in the Acknowledgements.

II!] NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


1.5.2. Guideline development steps

Systematic review Following the process outlined in the WHO handbook for guideline development (38), evidence was identified, synthesized and presented in a comprehensive and unbiased manner. Based on the list of specific NPls provided by the steering group, a systematic review was conducted for each NPI using four databases {MEDLINE, PubMed, EMBASE and Cochrane Library) and the Cochrane Central Register of Controlled Trials {CENTRAL).

The review steps were as follows: 1. Developing research questions, and inclusion or exclusion criteria. 2. Searching for any systematic review published within 5 years {i.e. since January 2014),

and updating that existing review if a recently published review was found. 3. Conducting a full systematic review if a recent review could not be identified. 4. Selecting articles and extracting data. Two independent reviewers screened all

titles and abstracts of the potentially relevant studies; if the studies described the effectiveness of NPls in reducing influenza virus transmission, the reviewers read the full-length text and extracted relevant data.

No language restriction was applied in the search. The specific search terms and criteria can be found in the Annex. Two reviewers independently screened titles, abstracts and full texts, and two reviewers independently conducted the data extraction for each study. If a consensus could not be reached, further discussion was held or an opinion was obtained from a third independent reviewer.

The systematic review explored the evidence base on the effectiveness of each NPI. The specific targets of the evidence included reducing transmission, delaying the start of the epidemic, delaying the peak of the epidemic, spreading out infections over a longer period, and reducing the total number of infections.

Evaluation of the evidence For each included study the risk of bias was assessed as part of the quality of evidence evaluation. In general, randomized controlled trials (RCTs) provided the strongest evidence, followed by observational studies and then computer simulations. The strength of individual studies could also be modified based on the risk of bias. The main types of bias in the systematic review of interventions are discussed below (39).

Potential limitations in RCTs include: lack of allocation concealment; lack of blinding; loss to follow-up and failure to adhere to the intention-to-treat principle; reporting bias; and lack of generalizability due to strict inclusion criteria.

Potential limitations in observational studies include: failure to describe the eligibility criteria; flaws in the measurement of exposure or outcome {or both); potential for bias due to confounding; and incomplete or inadequate follow-up.

----------------~ WORLD HEALTH ORGANIZATION LIJll


The Grading of Recommendations Assessment, Development and Evaluation {GRADE) (40) approach was used to rate the quality of evidence for each NPI, based on the question of whether NPls can reduce influenza transmission in the community. The quality of evidence was ranked as high, moderate, low or very low, based on each study's risk of bias {including publication bias), consistency, directness and precision of results (40). Two reviewers independently assessed the risk of bias and the quality of evidence. Disagreements were resolved by a third reviewer if consensus could not be reached.

Development of recommendations A technical consultation meeting for the development of this guidance was held in Hong Kong Special Administrative Region {SAR), China, on 26-28 March 2019. The systematic review team presented the outcomes of the systematic review. Recommendations were formulated by the guideline development group to determine the direction and strength of a recommendation by six indicators according to the WHO handbook for guideline development (38); the indicators are quality of the evidence, values and preferences, balance of benefits and harms, resource implications, acceptability and feasibility. In addition, ethical issues were taken into consideration. The strength of recommendations expressed the confidence of the guideline development group members in balancing desirable and undesirable consequences, which were classified as:

"recommendedn - the group is confident that the desirable effects outweigh the undesirable results;

"conditionally recommendedn - the group believes that the balance between benefits and harms is uncertain, and some conditions should apply when implementing the recommendation; or

"not recommended" - the group is confident that the disadvantages outweigh the advantages.



EJ SUMMARY OF RECOMMENDATIONS The eighteen recommendations, which fall under 15 measures, are summarized in Table 4. The recommendations are based on the quality of evidence, which is indicated within the table, and on the other indicators (i.e. values and preferences, balance of benefits and harms, resource implications, acceptability, feasibility and ethical considerations).

Table 4. Summary of recommendations for each NPI

MEASURES

Hand hygiene

Respiratory etiquette

RECOMMENDATIONS

Hand hygiene is recommended as part of general hygiene and infection prevention, including during periods of seasonal or pandemic influenza. Although RCTs have not found that hand hygiene is effective in reducing transmission of laboratory-confirmed influenza specifically, mechanistic studies have shown that hand hygiene can remove influenza virus from the hands, and hand hygiene has been shown to reduce the risk of respiratory infections in general.

Respiratory etiquette is recommended at all times during influenza epidemics and pandemics. Although there is no evidence that this is effective in reducing influenza transmission, there is mechanistic plausibility for the potential effectiveness of this measure.

QUALITY OF EVIDENCE

Moderate (lack of effectiveness in reducing influenza transmission)

None

STRENGTH OF RECOMMENDATION

Recommended

Recommended

I

I

WHEN TO APPLY

At all times

At all times

----------------~ WORIIJ HEALTH OW,I\Nl71\Tl(IN L&;,i

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MEASURES RECOMMENDATIONS

Face masks Face masks worn by asymptomatic people are conditionally recommended in severe epidemics or pandemics, to reduce transmission in the community. Although there is no evidence that this is effective in reducing transmission, there is mechanistic plausibility for the potential effectiveness of this measure.

A disposable surgical mask is recommended to be worn at all times by symptomatic individuals when in contact with other individuals. Although there is no evidence that this is effective in reducing transmission, there is mechanistic plausibility for the potential effectiveness of this measure.

Surface Surface and object cleaning and object measures with safe cleaning cleaning products are recommended as a

public health intervention in all settings in order to reduce influenza transmission. Although there is no evidence that this is effective in reducing transmission, there is mechanistic plausibility for the potential effectiveness of this measure.

QUALITY OF EVIDENCE



Low (lack of effectiveness in reducing influenza transmission)


Conditionally recommended

Recommended

Recommended


WHEN TO APPLY

In severe epidemics or pandemics

At all times for symptomatic individuals

At all times

I


Other Installing UV light in enclosed and environmental crowded places (e.g. educational

)> measures institutions and workplaces) is "'O "'O not recommended for reasons of m feasibility and safety. z 0

Increasing ventilation is X ~ recommended in all settings to 0 reduce the transmission of influenza c.... virus. Although there is no evidence )> that this is effective in reducing s:: m transmission, there is mechanistic en plausibility for the potential () effectiveness of this measure. )> en () There is no evidence that modifying )> humidity (either increasing humidity z in dry climates, or reducing humidity 0 in hot and humid climates) is an 0 effective intervention, and this is not m () recommended because of concerns s;: about cost, feasibility and safety.

! Contact tracing Active contact tracing is not

0 recommended in general because

z there is no obvious rationale for it in I most Member States. This intervention (.-)

CX> could be considered in some ~

locations and circumstances to collect information on the characteristics of the disease and to identify cases, or to delay widespread transmission in the very early stages of a pandemic in isolated communities.

WORI [) Hf Al TH OR(JANl?ATION

QUALITY OF EVIDENCE

None

Very low (effective)

None

Very low (unknown)


Not recommended

Recommended

Not recommended

Not recommended

I

WHEN TO APPLY

N/A

At all times

N/A

N/A

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MEASURES

Isolation of sick individuals

Quarantine of exposed individuals

School measures and closures

RECOMMENDATIONS

Voluntary isolation at home of sick individuals with uncomplicated illness is recommended during all influenza epidemics and pandemics, with the exception of the individuals who need to seek medical attention. The duration of isolation depends on the severity of illness (usually 5-7 days) until major symptoms disappear.

Home quarantine of exposed individuals to reduce transmission is not recommended because there is no obvious rationale for this measure, and there would be considerable difficulties in implementing it.

School measures (e.g. stricter exclusion policies for ill children, increasing desk spacing, reducing mixing between classes, and staggering recesses and lunchbreaks) are conditionally recommended, with gradation of interventions based on severity. Coordinated proactive school closures or class dismissals are suggested during a severe epidemic or pandemic. In such cases, the adverse effects on the community should be fully considered (e.g. family burden and economic considerations), and the timing and duration should be limited to a period that is judged to be optimal.

QUALITY OF EVIDENCE


Very low (variable effectiveness)

Very low (variable effectiveness)


Recommended

Not recommended


II] NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA

WHEN TO APPLY

At all times

N/A

Gradation of interventions based on severity; school closure can be considered in severe epidemics and pandemics


Workplace Workplace measures (e.g. measures and encouraging teleworking from home,

)> closures staggering shifts, and loosening '1J policies for sick leave and paid leave) '1J are conditionally recommended, with m z gradation of interventions based on CJ severity. Extreme measures such as X workplace closures can be considered -I in extraordinarily severe pandemics in 0 c.... order to reduce transmission. )> s: Avoiding Avoiding crowding during moderate m crowding and severe epidemics and pandemics en C') is conditionally recommended, with )> gradation of strategies linked with en severity in order to increase the C')

)> distance and reduce the density

z among populations. 0 CJ Travel advice Travel advice is recommended for m citizens before their travel as a public C')

s; health intervention in order to avoid potential exposure to influenza and

! to reduce the spread of influenza.

0 Entry and exit Entry and exit screening for z screening infection in travellers is not I w recommended, because of 0) a, the lack of sensitivity of these

measures in identifying infected but asymptomatic (i.e. pre-symptomatic) travellers.

WORi D HF Al TH ORC,ANI? ATION

QUALITY OF EVIDENCE


Very low (unknown)

None

Very low (lack of effectiveness in reducing influenza transmission)



------ ----·----·-·· -- - ·-


Recommended

Not Recommended

WHEN TO APPLY

Gradation of interventions based on severity; workplace closure should be a last step only considered in extraordi-narily severe epidemics and pandemics

Moderate and severe epidem-ics and pandemics

Early phase of pandemics

N/A

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I MEASURES

Internal travel restrictions

Border closure

RECOMMENDATIONS

Internal travel restrictions are conditionally recommended during an early stage of a localized and extraordinarily severe pandemic for a limited period of time. Before implementation, it is important to consider cost-effectiveness, acceptability and feasibility, as well as ethical and legal considerations in relation to this measure.

Border closure is generally not recommended unless required by national law in extraordinary circumstances during a severe pandemic, and countries implementing this measure should notify WHO as required by the IHR (2005).

QUALITY OF EVIDENCE

Very low (effective}

Very low (variable effectiveness}



Not recommended

WHEN TO APPLY

Early phase of extraordinarily severe pandemics

N/A

IHR: International Health Regulations; N/A: not applicable; NPI: non-pharmaceutical intervention; RCT: randomized controlled trial; UV: ultraviolet; WHO: World Health Organization.

II] NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA

COMMUNICATION FOR BEHAVIOURAL IMPACT

Communication for behavioural impact (COMBI) (4 7) is a planning framework and an implementation method for using communication strategically to achieve positive behavioural and social results. It involves health education, health literacy, health promotion, risk communication and social mobilization, and it plays a critical role in the implementation of the NPI measures by modifying behaviour. COMBI identifies the barriers and constraints that prevent people from choosing to adopt healthy behaviour, and ensures that communication is appropriately applied and can contribute to achieving expected behavioural impact.

In the implementation of the recommended NPI measures, COMBI should be used to: • share the rationale; • encourage active engagement; • empower people with information; • adapt recommendations to the local context; and • quickly develop effective communication strategies, messages and materials, using existing

resources and partnerships.

The rest of this section discusses each of these points.

Share the rationale This involves explaining to people why certain behaviour is important. Transparency in sharing information and its rationale helps to build trust and increases the likelihood of cooperation.

Encourage active engagement This involves: • encouraging people to seek information from credible sources; and • ensuring that neighbours, communities and networks receive and understand accurate

information, report possible influenza cases and help communities in managing ill people.

In this approach, people are viewed as "partners in prevention~ rather than simply as recipients of information. The approach is therefore likely to create ownership, resulting in better adoption of recommended behaviours and more proactive communities. Such partners in prevention are also more likely to find creative ways to mobilize community resources and help build capacity that might be useful in the future.

Empower people with information People and communities will take their own decisions on the basis of the balance of forces of their own circumstances. The communication approach should emphasize information sharing and community problem solving as ways of helping people to find a set of doable actions, so that they ask"How can we effectively prevent infection and protect ourselves, our families and our community?0

Adapt recommendations to the local context It is important to take into account people's capacity to act on the advice being given. The recommended behaviour must be doable and be adapted to people's lifestyle; otherwise, it will not be widely adopted. For example, there is a need to ensure that marginalized groups (e.g. those living in inadequate or overcrowded housing, religious minorities and people beyond the reach of

________________ m WORLD HEALTH ORGANIZATION W


the mass media) are also engaged in prevention and protection, have access to information and have the capacity to act upon it.

Use existing resources and partnerships to quickly develop effective communication strategies, messages and materials Working through existing communication and coordination bodies makes it easier to harmonize messages, approaches and use of channels. It is important to invest resources in understanding the current knowledge, attitude and practices on the implementation of NPls - this can help to reduce the impact of pandemic and thus craft policy and workflow to more effectively manage the public's concerns, compliance and expectations. In turn, this may help Member States to achieve a higher effectiveness for these NPls. Training on crisis communication for selected community leaders and key national stakeholders as part of pandemic preparedness is also important.

PERSONAL PROTECTIVE MEASURES This section covers three types of personal protective measures: hand hygiene, respiratory etiquette and face masks.

4.1. Hand hygiene

Summary of evidence Twelve articles describing 11 RCTs (two studies were the same project during the same period but studied different questions) of hand hygiene were included in a systematic review, and a metaanalysis was undertaken of 1 0 studies including more than 11 000 participants in total (42-53). It was not possible to make a pooled estimate of the effectiveness of hand hygiene with or without face masks because of the high heterogeneity (see Annex). In the pooled analysis of six studies that examined hand hygiene together with face masks, there was no statistically significant protective effect when all settings outside of health care were combined (rate ratio [RR]: 0.91, 95% confidence interval [Cl]: 0.73-1.13, P=0.39, 12=35%) (42-47). Two studies were conducted in an elementary school setting but had very different findings: one study conducted in the USA found no significant effect of hand hygiene, with a precise estimate of the risk ratio close to 1; in contrast, a large trial in Egypt reported a statistically significant reduction of more than 50% in laboratoryconfirmed influenza cases in the intervention group (RR: 0.47, 95% Cl: 0.39-0.56, P<0.01) (48, 49). Two studies in university halls of residence found no statistically significant effect of hand hygiene with face masks (RR: 0.48, 95% Cl: 0.21-1.08, P=0.08, 12=0%) (42, 43). In addition, in household settings the efficacy of hand hygiene with or without a face mask was not significant (RR: 1.05, 95% Cl=0.86-1.27, P=0.65, 12=57%) (44-47, 50, 57). Several trials reported that poor adherence to hand hygiene may contribute to the low efficacy observed (44-46).

Influenza virus can survive for a short time on human hands and transmit from contaminated surfaces to hands, supporting the potential for contact transmission to occur (54-56). Hand hygiene is effective to inactivate or reduce viable influenza virus on human hands (57-59). In theory, hand hygiene could prevent indirect contact transmission of influenza; however, hand hygiene adherence is often suboptimal, even in intervention studies.

Testing the efficacy of hand hygiene in RCTs is complicated by the fact that the comparison groups cannot be asked to stop washing their hands. Thus, evidence from RCTs is typically based on either an increase in the quantity of hand hygiene episodes or non-inferiority trials focusing on certain products (e.g. hand sanitizer in combination with hand washing versus hand washing alone), making it difficult to estimate the efficacy of hand hygiene alone. Within this context, existing

EilJ NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


hand hygiene studies are of a moderate overall quality, and they do not provide strong evidence that increased hand hygiene or different hand hygiene modalities are highly effective at reducing influenza. However, there are several experimental studies (57-60) that provide evidence that hand hygiene can inactivate or remove influenza and therefore reduce transmission.

OVERALL RESULT OF EVIDENCE ON HAND HYGIENE

1. Eleven RCTs were included in this review. Although hand hygiene was not effective against laboratory-confirmed influenza in a meta-analysis in community settings and university halls, it was effective in one of two trials conducted in schools.

2. Although compliance with optimal (intense) hand hygiene practices was imperfect in these RCTs, compliance with proper hand hygiene might not be substantially higher in community settings, even in severe influenza epidemics and pandemics.

3. Experimental studies suggested that hand hygiene could effectively inactivate or reduce influenza virus on hands; hence, theoretically, hand hygiene could prevent influenza transmission.

Summary of considerations of members of the guideline development group for determining the direction and strength of the recommendations The guideline development group, with the support of the steering group, formulated recommendations that were informed by the evidence presented and took into account quality of evidence, values and preferences, balance of benefits and harms, resource implications, ethical considerations, acceptability and feasibility, as outlined below.

Quality of evidence There is a moderate overall quality of evidence that hand hygiene does not have a substantial effect on transmission of laboratory-confirmed influenza.

Values and preferences It is well-established that hand hygiene can substantially reduce many important infectious diseases, particularly diarrhoeal diseases, and there is good evidence that hand hygiene can also reduce respiratory illnesses, although not laboratory-confirmed influenza. Hand hygiene is most often performed with water and soap; alcohol-based hand sanitizers are another option for waterless hand disinfection in some locations. Most communities would understand the importance and effectiveness of hand hygiene in preventing common infections, and would agree with the concept of encouraging hand hygiene to prevent infection, although education campaigns might be needed in some communities.

Balance of benefits and harms Hand hygiene had no significant effect on transmission of laboratory-confirmed influenza, other than in the RCT in schools in Egypt. The guideline development group concluded that, in general, the evidence from controlled trials indicates that hand hygiene is not effective in preventing laboratory-confirmed influenza, but it is possible that a major change in hand hygiene from a very low level to a very high level might reduce influenza transmission. Hand hygiene does prevent transmission of other infections, including diarrhoeal and respiratory diseases, and can substantially improve public health (61 ). There are no adverse effects of hand hygiene, other than possible soap or alcohol allergies (62).



Resource implications Hand hygiene is one of the most cost-effective measures for preventing infections in health care settings (63). It is an important component of general hygiene campaigns in communities, and can reduce the incidence of a variety of infections and associated morbidity and mortality. Clean running water is not available in some communities and would be a barrier. Alcohol hand-rub may be too expensive in some settings.

Ethical considerations There are no major ethical issues regarding hand hygiene with soap and water. Alcohol-based hand-rub might not be permitted in some locations due to religious objections (64).

Acceptability More than half of published national pandemic plans have included hand hygiene as a prevention measure (65). Given the low cost and broad impact on infections, it is a very acceptable intervention. However, the guideline development group considered that compliance and adherence is low (especially compliance to proper hand hygiene practice) because it is hard to make substantial behavioural changes.

Feasibility Many countries have already conducted public hand hygiene campaigns to reduce communicable diseases (65). This intervention is considered to be very feasible.

RECOMMENDATION:

Hand hygiene is recommended as part of general hygiene and infection prevention, including during periods of seasonal or pandemic influenza. Although RCTs have not found that hand hygiene is effective in reducing transmission of laboratory-confirmed influenza specifically, mechanistic studies have shown that hand hygiene can remove influenza virus from the hands, and hand hygiene has been shown to reduce the risk of respiratory infections in general.

Population: General public

When to apply: At all times

FACTORS ASSESSMENT RATIONALE

Quality of evidence

Values and preferences


Favourable Favourable

Moderate quality of evidence from 1 O RCTs in a meta-analysis involving > 11 000 participants that hand hygiene is ineffective in reducing influenza transmission in the community, although experimental studies suggested that hand hygiene could theoretically prevent influenza transmission.

Hand hygiene has an established effect on common diarrhoeal infections and can also reduce some respiratory infections and other infections.

EE NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA



Balance of benefits and harms

Resource implications

Ethical considerations

Acceptability

Feasibility

Overall strength of recommendation

Favourable

Favourable

Conditional

Favourable

Favourable

Recommended

No important adverse effects of hand hygiene with water and soap, other than possible soap or alcohol allergies.

Hand hygiene with soap and water is generally very cost-effective given the reduction in common infections and no additional equipment is needed.

No major ethical issues. There may be religious objections to alcohol hand-rub.

No major concerns with acceptability, but the compliance and adherence of this intervention may be difficult to change substantially.

Very feasible because it is normal practice.

Although hand hygiene does not have proven efficacy against laboratoryconfirmed influenza in RCTs, it is recommended because it has been shown to deadivate or remove influenza virus from the hands in experimental studies, and can reduce the burden of those other infedions on the health system during influenza epidemics and pandemics.

Knowledge gaps: There are important gaps in our knowledge of the mechanisms of personto-person transmission of influenza, including the importance of direct and indirect contact, the degree of viral contamination on hands and various types of surfaces in different settings, and the potential for contact transmission to occur in different locations and under different environmental conditions. Additional research on increasing hand hygiene compliance would also be valuable. There is little information on whether greater reductions in transmission could be possible with combinations of personal interventions (e.g. isolation away from family members as much as possible, plus using face masks and enhancing hand hygiene).

RCT: randomized controlled trial.



4.2. Respiratory etiquette

Summary of evidence Respiratory etiquette refers to the actions used when people cough or sneeze (66); it is a simple hygiene practice to prevent person-to-person transmission of respiratory infections. Measures include (6n covering the mouth and nose with a hand, sleeve or tissue when coughing or sneezing; finding the nearest waste basket to dispose of the used tissue immediately; and washing hands after touching respiratory secretions or contaminated objects (or both). A total of 80 articles were retrieved from four electronic databases, and no scientific studies were identified for inclusion in this review.

Respiratory etiquette is a common and acceptable practice in relation to personal hygiene; however, there is no research on the effectiveness of respiratory etiquette on the reduction of laboratory-confirmed influenza virus infection.


Quality of evidence The quality of evidence could not be judged because no study was identified.

Values and preferences Respiratory etiquette and hygiene is recognized as important in many communities. Improvements in respiratory etiquette in communities could prevent the spread of a variety of infections.

Balance of benefits and harms There are no anticipated harms of improved respiratory etiquette.

Resource implications Efforts to improve respiratory etiquette in communities would not be expensive and could be included as part of broader public health campaigns.

Ethical considerations There are no major ethical considerations in relation to respiratory etiquette. Cultural contexts may be considered when recommending specific actions such as covering coughs with hands or tissues.

Acceptability Improved respiratory etiquette should be acceptable in most locations.

Feasibility This is a feasible intervention, and respiratory etiquette campaigns have been successful for acute respiratory infections (66). Furthermore, 32 Member States have included respiratory etiquette in their national pandemic preparedness plans (65).

EIJ NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


r

RECOMMENDATION:

Respiratory etiquette is recommended at all times during influenza epidemics and pandemics. Although there is no evidence that this is effective in reducing influenza transmission, there is mechanistic plausibility for the potential effectiveness of this measure.




Quality of evidence





Acceptability

Feasibility


None

Conditional

Favourable

Favourable

Favourable

Favourable

Favourable

Recommended

No scientific evidence on the effectiveness of respiratory etiquette.

Respiratory etiquette is a simple personal protective measure to prevent infection, but may not always be recognized as important in some cultures and locations.

No anticipated harms.

No significant costs for the general public.

There are no major ethical considerations. Cultural contexts and norms may be considered when recommending specific actions such as covering coughs with hands or tissues.

No major concerns with acceptability.

Highly feasible.

Although there is no research on the impad of respiratory etiquette on laboratory-confirmed influenza lnfedlon, this is a simple, feasible and acceptable intervention that may reduce transmission and reduce the impad of epidemics and pandemics.



Knowledge gaps: There is still no evidence about the quantitative effectiveness of respiratory etiquette against influenza virus. RCTs of interventions to improve respiratory etiquette would be valuable.


4.3. Face masks

Summary of evidence Ten relevant RCTs were identified for this review and meta-analysis to quantify the efficacy of community-based use of face masks, including more than 6000 participants in total (42-47, 50, 68-70). Most trials combined face masks with improved hand hygiene, and examined the use of face masks in infected individuals (source control) and in susceptible individuals. In the pooled analysis, although the point estimates suggested a relative risk reduction in laboratory-confirmed influenza of 22% (RR: 0.78, 95% Cl: 0.51-1.20, 12=30%, P=0.25) in the face mask group, and a reduction of 8% in the face mask group regardless of whether or not hand hygiene was also enhanced (RR: 0.92, 95% Cl=0.75-1.12, 12=30%, P=0.40), the evidence was insufficient to exclude chance as an explanation for the reduced risk of transmission. Some studies reported that low compliance in face mask use could reduce their effectiveness. A study suggested that surgical and N95 (respirator) masks were effective in preventing the spread of influenza (77).

r OVERALL RESULT OF EVIDENCE ON FACE MASKS

1. Ten RCTs were included in the meta-analysis, and there was no evidence that face masks are effective in reducing transmission of laboratory-confirmed influenza.


Quality of evidence There is a moderate overall quality of evidence that face masks do not have a substantial effect on transmission of influenza.

Values and preferences Face mask use is common to prevent transmission of infections in health care settings around the world, and a widely used measure in some communities, particularly in South-East Asia.

Balance of benefits and harms There are no major adverse effects of face mask use. There might be issues with allergies in some individuals, and prolonged use of face masks can be uncomfortable or inconvenient.

Resource implications Reusable cloth face masks are not recommended. Medical face masks are generally not reusable, and an adequate supply would be essential if the use of face masks was recommended. If worn by a symptomatic case, that person might require multiple masks per day for multiple days of illness.



Ethical considerations There are no major ethical considerations in the use of face masks. Masks may be more culturally acceptable in some locations, and other health behaviours may affect compliance (72).

Acceptability Face masks are widely used in health care settings to prevent transmission of infections, and are used in the community in some parts of the world (65). They are likely to be acceptable if recommended, particularly in more severe epidemics and pandemics. However, face masks are not appropriate under some circumstances (e.g. during sleep). The guideline development group also considered that compliance may not be high in some areas and populations.

Feasibility Twenty-eight Member States have included the use of face masks in their national influenza preparedness plan (65). Feasibility can be enhanced by education campaigns to improve usage and compliance. The guideline development group believed that this intervention is feasible, especially for symptomatic individuals.

RECOMMENDATION:

Face masks worn by asymptomatic people are conditionally recommended in severe epidemics or pandemics, to reduce transmission in the community. Disposable, surgical masks are recommended to be worn at all times by symptomatic individuals when in contact with other individuals. Although there is no evidence that this is effective in reducing transmission, there is mechanistic plausibility for the potential effectiveness of this measure.

Population: Population with symptomatic individuals; and general public for protection

When to apply: At all times for symptomatic individuals (disposable surgical mask), and in severe epidemics or pandemics for public protection (face masks)


Quality of Moderate (lack of According to the GRADE approach, evidence effectiveness in there was moderate quality of evidence

reducing influenza involving >6000 participants that face transmission) masks are ineffective in reducing influenza

transmission in the community. -~--·--~----~-

Values and Favourable Masks can be worn by symptomatic or preferences exposed persons to reduce transmission

(source control), or by uninfected persons in the community to reduce their risk of infection.

Balance of Favourable No significant harms anticipated. benefits and harms

Resource Conditional Costly in some settings, and supplies may implications be limited.





Acceptability

Feasibility

Favourable

Conditional

Conditional ------r

No major ethical considerations.

Likely to be acceptable, but not appropriate in some circumstances and the adherence and compliance is low.

Dependent on availability, but more feasible for symptomatic individuals.

r Overall strength of recommendation

Recommended for symptomatic individuals, and conditionally recommended for public protection

Given the costs and the uncertain effectiveness, face masks are conditionally recommended only in severe influenza epidemics or pandemics for the protection of the general population, but are recommended for symptomatic individuals at all times .

... r

Knowledge gaps: There are important gaps in our knowledge of the mechanisms of personto-person transmission of influenza, including the importance of transmission through droplets of different sizes including small particle aerosols, and the potential for droplet and aerosol transmission to occur in different locations and with different environmental conditions. Additional high-quality RCTs of the efficacy of face masks against laboratoryconfirmed influenza would be valuable.

GRADE: Grading of Recommendations Assessment, Development and Evaluation; RCT: randomized controlled trial.

(J ENVIRONMENTAL MEASURES 5.1. Surface and object cleaning

Summary of evidence Three studies were included in the systematic review to study the effectiveness of surface and object cleaning in reducing influenza transmission (73-75). An RCT with disinfection of toys and linen in day care facilities found a reduction in the detection of viruses in the environment, but no significant effect on laboratory-confirmed influenza or acute respiratory illnesses among children (74). Another RCT conducted in elementary schools reported that surface disinfection combined with hand hygiene could reduce absenteeism due to gastrointestinal illness, but not absenteeism due to respiratory illness (75). A cross-sectional study showed that passive contact with sodium hypochlorite (bleach) in households was significantly associated with an increase in the rate of self-reported influenza, which the authors of the article hypothesized had occurred due to the immunosuppressive properties of bleach (73).



Influenza virus can survive on surfaces and objects for a few hours and up to 1 week (54, 55, 76-78). Influenza virus RNA has been detected in various settings outside of health care settings, but little of the RNA was found to be viable (74, 79-83). Surface and object cleaning is effective at inactivating or reducing viable influenza virus on surfaces (84-86). In theory, surface and object cleaning could prevent indirect contact transmission of influenza.

r OVERALL RESULT OF EVIDENCE ON SURFACE AND OBJECT CLEANING

1. Two RCTs and one cross-sectional study were included in the systematic review.

2. There was evidence that surface and object cleaning could reduce detections of virus in the environment, but there was no evidence of effectiveness against laboratory-confirmed influenza virus infection.

3. Experimental studies suggested that surface and object cleaning could effectively inactivate or reduce viable influenza virus on surfaces; theoretically, this intervention could prevent influenza transmission.


Quality of evidence There is a low overall quality of evidence that cleaning of surfaces and objects does not have a substantial effect on transmission of respiratory disease.

Values and preferences A telephone survey in Europe found that most (8296) participants believed that cleaning or disinfecting objects might reduce the risk of influenza (87). Environmental cleaning is a common strategy to reduce a variety of infections.

Balance of benefits and harms Cleaning using detergent-based cleaners or bleach can inactivate or remove influenza viruses from surfaces and objects, and in theory could reduce influenza transmission. However, most disinfectants (e.g. bleach} require a pre-cleaning step before the disinfectant is applied, and it is not safe to add water to chlorine solutions (88, 89). Incorrect use of disinfectants and poor ventilation when using the disinfectant can be harmful (29).

Resource implications The implementation of surface and object cleaning would involve relatively minor resources. The cost of disinfectants is relatively low.

Ethical considerations Cleaning product selection is a major issue. Some disinfectants are irritants and may lead to adverse effects in sensitive populations (73); also, they may not be applicable in some countries or regions due to the prohibition of alcohol (64). However, most countries have no legislation restricting the use of alcohol in household cleaning agents, and even in Muslim tradition, alcohol is permitted as a cleansing ingredient (64). In addition, the safety of cleaning personnel should also be considered.

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Acceptability This intervention is highly accepted by policy-makers and health workers worldwide. However, the acceptability may vary among different countries.

Feasibility This intervention is highly feasible. Disinfectants are available from a variety of sources, such as general supermarkets or convenience stores.

RECOMMENDATION:

Surface and object cleaning measures with safe cleaning products are recommended as a public health intervention in all settings in order to reduce influenza transmission. Although there is no evidence that this is effective in reducing transmission, there is mechanistic plausibility for the potential effectiveness of this measure.

Population: General population



Quality of evidence





Acceptability

Feasibility

Low (lack of effectiveness in reducing influenza transmission)

Favourable

Conditional

Favourable

Conditional

Favourable

Favourable

i

I

:

!

i

Very limited evidence on the effectiveness or lack of effectiveness of environmental cleaning. Surface and object cleaning is ineffective in reducing respiratory disease transmission in the community, although experimental studies suggest that theoretically surface and object cleaning could prevent influenza transmission.

Likely to be perceived as a simple but important measure, if recommended.

Safety concerns with some cleaning products.

The cost of disinfectants is low.

In some locations, cleaning with alcohol may not be allowed, but other chemicals can be used.

-------~~---

Likely to be acceptable if recommended.

Disinfectants can be obtained from various sources.

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r


Recommended There are no major disadvantages of surface and object cleaning, so this measure Is recommended despite the lack of evidence on effectiveness.

Knowledge gaps: Only three studies were included in our systematic review and only two of them were RCTs. More trials are needed to study the effect of surface and object cleaning on influenza prevention. The best evidence of pandemic preparedness would be provided by studies in which the outcome is laboratory-confirmed influenza, rather than acute respiratory infections. Studies are needed in various settings (e.g. household, school, workplace and public place). The effectiveness of different cleaning products in preventing influenza transmission - in terms of cleaning frequency, cleaning dosage, cleaning time point, and cleaning targeted surface and object material - remains unknown.


5.2. Other environmental measures

5.2.1. Ultraviolet light Summary of evidence The systematic review did not identify any studies that quantified the effectiveness of ultraviolet (UV) light in reducing influenza transmission. UV light is a means of disinfection; it breaks down microorganisms and can be used to prevent the spread of certain infectious diseases (90).


Quality of evidence The quality of evidence could not be judged because no study was identified.

Values and preferences The guideline development group noted that UV light intervention would not be useful if the surface is covered, and would probably have a limited impact on transmission given the likely modes of influenza transmission.

Balance of benefits and harms The effectiveness of UV light against influenza transmission is uncertain. Exposure to UV light may increase the risk of skin cancers and eye problems (91 ). The guideline development group considered UV light intervention to be harmful in some circumstances.

Resource Implications Installing and maintaining UV light fixtures is expensive. However, the guideline development group believed that costs in settings with a large number of people (e.g. public transport) may be reasonable given the potential impact.



r

Ethical considerations No major ethical concerns were identified in relation to the use of UV light.

Acceptability The use of UV light to reduce influenza transmission by disinfection of the environment is likely to have limited acceptability, because of the costs and complexity of installation and maintenance. The guideline development group believed it would be unlikely that these fixtures could be installed at short notice, such as in the early stages of an influenza pandemic.

Feasibility The use of UV disinfection is hindered by safety concerns.

RECOMMENDATION:

Installing UV light in enclosed and crowded places (e.g. educational institutions and workplaces) is not recommended for reasons of feasibility and safety.

Population: People exposed to risk in closed and crowded places

When to apply: N/ A


Quality of None No study was identified in the review. evidence

Values and Conditional Uncertain. preferences

Balance of Conditional Safety concerns. benefits and harms

Resource Conditional Substantial costs associated with installing implications and maintaining UV light fixtures.

Ethical Conditional No major ethical concerns. considerations

Acceptability Conditional Uncertain acceptability given costs and complexity of installation and maintenance.

--

Feasibility Conditional UV light may not be feasible because of high costs and safety concerns.



r

r


Not Recommended The use of UV light is hindered by feasibility and safety concerns.

Knowledge gaps: The effectiveness of UV light in reducing influenza transmission still requires more evidence. Potential safety issues are also an important consideration and more scientific evidence is needed to confirm effectiveness and feasibility as a community mitigation measure for influenza epidemics and pandemics.

N/ A: not applicable; UV: ultraviolet.

5.2.2. Increased ventilation Summary of evidence A simulation study predicted a reduction of transmission among kindergarten students by enhancing the air changes per hour (ACH) (92). Two simulation studies evaluated the effectiveness of increasing ventilation in reducing influenza transmission in community settings (93, 94). One of these two studies suggested a reduction of daily peak infections by increasing ACH under the baseline scenario (93), and the other predicted that the peak infection rate could be reduced by more than 60% by doubling or tripling the ventilation rate (94).

OVERALL RESULT OF EVIDENCE ON INCREASED VENTILATION

1. In simulation studies, increasing the ventilation rate reduced influenza transmission.

2. There is mechanistic plausibility for increased ventilation to reduce transmission - specifically aerosol transmission and perhaps to a lesser extent large respiratory droplet transmission or indirect contact transmission.


Quality of evidence There is a very low overall quality of evidence that increasing ventilation has an effect on transmission of influenza.

Values and preferences Increasing ventilation is a common practice in many locations, for a multitude of reasons.

Balance of benefits and harms There is no major harm associated with increased ventilation. Airflow pattern and flow direction are important considerations (95). If the outdoor temperature is very low, thermal comfort may be an issue. Exposure to air pollution and allergens may trigger asthmatic attacks.

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Resource implications The cost of opening windows is likely to be low. There may be costs associated with increasing ventilation for buildings or homes with mechanical ventilation (e.g. increased electricity costs). In cold climates, increased natural or mechanical ventilation could also increase heating costs.

Ethical considerations There are no major ethical considerations associated with the use of increased ventilation.

Acceptability The acceptability of increased ventilation is likely to be high.

Feasibility Increased ventilation is likely to be feasible in most settings.

RECOMMENDATION:

Increasing ventilation is recommended in all settings to reduce the transmission of influenza virus. Although there is no evidence that this is effective in reducing transmission, there is mechanistic plausibility for the potential effectiveness of this measure.

Population: General Population


Values and Favourable preferences

Balance of Conditional benefits and harms

Resource Conditional implications

Ethical Favourable considerations

Acceptability Favourable

Feasibility Conditional

The only evidence was provided by simulation studies. In those studies, increased ventilation was predicted to be effective in reducing influenza transmission in the community.

Commonly used intervention.

Exposure to air pollution and allergens may trigger asthmatic attacks.

May lead to increased heating costs or increased electricity costs.

No major ethical considerations.

Increased ventilation is highly accepted.

Increased ventilation is feasible in most locations.

EIJ NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA



Recommended Effectiveness is uncertain, but Increased ventilation Is simple and feasible in most locations.

Knowledge gaps: Simulation models provide a weak level of evidence. RCTs would provide more compelling evidence on the efficacy of increasing ventilation in reducing influenza transmission.


5.2.3. Modifying humidity Summary of evidence Increased humidity has been correlated with reduced influenza transmission in cold and dry climates (96, 97), and very high humidity has been associated with increased transmission in hot and humid climates ( 7 7). Nevertheless, no study was identified in the review that quantified the effectiveness of modifying humidity (as an intervention) in reducing influenza transmission.

Elevated humidification (absolute humidity at 9 millibars) was shown to reduce influenza A virus detections in the air and on fomite (markers and wooden toys) in a preschool classroom (97). A simulation study also predicted a 17.5-31.6% reduction of influenza virus survival in rooms with a humidifier operating in a residential setting (98). Another simulation study predicted that nearly five times more influenza virus from stimulated coughs would remain infectious at 7-23% relative humidity (RH) than at an RH of more than 43% in a 1-hour collection (99).


Quality of evidence The quality of evidence cannot be judged because no study was identified in the review.

Values and preferences Uncertain.

Balance of benefits and harms Humidification may increase the growth of mould and mildew, harming health ( 700). According to WHO, indoor dampness or mould creates a considerable health burden (e.g. asthma) in children (707).

Resource implications Humidifiers are expensive to purchase and maintain.

Ethical considerations There are no major ethical considerations in relation to modifying humidity.

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r

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Acceptability Modifying humidity is likely to be acceptable.

Feasibility There may be insufficient availability of humidifiers at short notice, and it may not be feasible to humidify buildings across a community.

RECOMMENDATION:

There is no evidence that modifying humidity (either increasing humidity in dry climates, or reducing humidity in hot and humid climates) is an effective intervention, and this is not recommended because of concerns about cost, feasibility and safety.

Population: N/ A

When to apply: N/ A


Quality of evidence





Acceptability -----~ --

Feasibility


None

Conditional

Conditional

Conditional

Favourable

Favourable

Conditional

Not Recommended

No study was identified in the review.

Uncertain.

Higher humidity may increase the growth of mould and mildew, causing harm.

Costly to purchase and maintain.

There are no major ethical considerations.

Likely to be acceptable.

Humidity may not be feasible as a population-level intervention.

The use of mechanical humidity is hindered by feaslblllty and safety reasons.

Knowledge gaps: The exact biological mechanism of how humidity affects the survival of the influenza virus is unclear (96, 97). Many studies have looked at the effect under laboratory conditions, but very few have tested these effects in natural settings. It would be informative to conduct RCTs of humidification as an intervention to reduce influenza transmission.

N/ A: not applicable; RCT: randomized controlled trial.

~ NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


SOCIAL DISTANCING MEASURES 6. 1. Contact tracing

Summary of evidence Four simulation studies were included in the systematic review (102-105), none of which studied contact tracing as a single intervention. Contact tracing was studied in combination with other interventions such as quarantine, isolation and provision of antiviral drugs. Evidence for the overall effectiveness of contact tracing varied. A simulation model with RO= 1.8 reported that the combination of contact tracing, quarantine, isolation and antiviral drugs could reduce the infection attack rate by 40% ( 7 02), while another study predicted that it would be difficult to control influenza even with 90% contact tracing and quarantine because of the presumed high level of pre-symptomatic or asymptomatic transmission ( 104). A combination of isolation, treatment of cases, contact tracing, quarantine and post-exposure prophylaxis was estimated to delay the epidemic peak for 6 weeks, assuming a case detection rate of 30% ( 7 05). In addition, the combination of contact tracing with quarantine has been suggested to be more effective than when combined with symptom monitoring (703).

OVERALL RESULT OF EVIDENCE ON CONTACT TRACING

1. Evidence for overall effectiveness of contact tracing was limited. All included studies were simulation models.

2. Only one study reported on the effect of adding contact tracing to isolation and quarantine. Such addition was estimated to provide at most a modest benefit, but at the same time would increase considerably the number of quarantined individuals.


Quality of evidence There is a very low overall quality of evidence that contact tracing has an unknown effect on the transmission of influenza.

Values and preferences There is uncertainty about the values and preferences of contact tracing among the community for control of influenza. Mandatory contact tracing may cause concerns and uneasiness to some cases and their contacts; however, voluntary reporting of contacts can prevent such concerns.

Balance of benefits and harms Contact tracing allows the rapid identification of at-risk individuals once a case has been detected. This intervention reduces the delay between symptom onset and treatment, as well as implementation of preventive measures for onward transmission ( 7 06). The guideline development group considered contact tracing to be a potentially important measure in reducing cross-border transmission. However, contact tracing on a large scale can lead to ethical issues such as leakage of information, and inefficient usage of resources, including human resources ( 10n.

-----------------------ED WORLD HEALTH ORGANIZATION


Resource implications Following up contacts of an infected individual who may have been exposed often has low costeffectiveness in the control of influenza, resulting in high direct costs. Considerable amounts of human resources are also needed for contact tracing.

Ethical considerations There are a few ethical issues surrounding the implementation of contact tracing as an intervention. Also, contact identification of infected individuals brings about privacy concerns (707). Some individuals may perceive stigma and refuse to be contact traced. Nevertheless, contact tracing may be justified, given that it allows the identification of persons at risk, and the timely provision of treatment and care (706, 707). There may be more ethical concerns when contact tracing is coupled with measures such as household quarantine. Contact tracing can substantially increase the proportion of people quarantined, but may not offer much additional benefit to existing interventions (702). In addition, contact tracing may not be an equitable intervention, because its successful implementation relies on availability of resources and technology.

Acceptability The evidence is limited and the acceptability of contact tracing among the public is uncertain.

Feasibility Contact tracing requires a large amount of trained personnel and resources (e.g. telecommunications); hence, it may be less feasible in low- to middle-income countries where resources are limited. In addition, the implementation and effectiveness of contact tracing rely on the capacity to detect cases, and contact tracing efforts are likely to be hampered by the short incubation and infectious periods of influenza (704). The triggers to activate and de-activate contact tracing for optimal effect in controlling influenza remain unknown.

,

\..

RECOMMENDATION:

Active contact tracing is not recommended in general because there is no obvious rationale for it in most Member States. This intervention could be considered in some locations and circumstances to collect information on the characteristics of the disease and to identify cases, or to delay widespread transmission in the very early stages of a pandemic in isolated communities.

Population: Individuals who have come into contact with an infected person

When to apply: N/ A


Quality of evidence


Very low (unknown)

Conditional

All included articles are simulation models and the inherent limitations lead to a very low quality of evidence. Contact tracing combined with other interventions is effective in reducing influenza transmission in the community, but the effect of contact tracing alone is unknown.

There is uncertainty or variability in the values and preferences among different interest groups.

EI: NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA






Acceptability

Feasibility


! Conditional

Conditional

Conditional

Conditional

Conditional

Not Recommended

Contact tracing can reduce onward transmission; however, the relevant ethical issues and inefficient usage of resources mean that the balance of benefits and harms is uncertain.

Contact tracing requires a large amount of resources, including human resources.

Privacy and equity concerns may exist for the implementation of contact tracing.

The acceptability of contact tracing among stakeholders is uncertain because of limited evidence.

Feasibility of contact tracing may be low when resources are limited; also, it is affected by the short incubation period of influenza.

There Is no obvious rationale in most Member States.

Knowledge gaps: There are few studies on the effectiveness of contact tracing on influenza in the community, and none that have studied contact tracing as a single intervention. Some epidemiological studies have documented contact tracing of air passengers and crew; however, the risk for influenza transmission onboard aircraft is still uncertain (708). Therefore, the effectiveness of contact tracing cannot be assessed from these studies. Moreover, currently available studies for community settings are all simulation studies - evidence of greater strength is needed to provide a more robust understanding of the effectiveness and value of contact tracing. Still unclear are the impacts of different intensities of contact tracing, and the optimal time frame, feasibility and cost-benefit.

N/ A: not applicable.



6.2. Isolation of sick individuals

Summary of evidence Terms relevant to isolation are defined below (Table 5).

Table S. Definition of terms relevant to isolation

TERM

Isolation

Case isolation

Patient isolation

Home isolation

Voluntary isolation

Self-isolation

DEFINITION

Separation or restriction of movement of ill persons with an infectious disease to prevent transmission to others ( 7 09).

Separation or restriction of movement of ill persons with an infectious disease at home or in a health care facility, to prevent transmission to others (29, 109).

Isolation of ill persons with an infectious disease in a health care facility, to prevent transmission to others (29).

Home confinement of ill persons with an infectious disease (often not needing hospitalization), to prevent transmission to others (29, 709).

Voluntary separation or restriction of movement of ill persons in a designated room to prevent transmission to others. This is usually in their own homes, but could be elsewhere (709).

See 'Voluntary isolation'.

The systematic review identified four epidemiological studies (110-113) and 11 simulation studies that were eligible for inclusion in our review (702, 104, 114-122).

Among the four epidemiological studies, a reduction in the cumulative incidence of infections and reproduction number due to an isolation policy was recorded during an influenza A(H 1 N 1 )pdm09 outbreak on a navy ship ( 7 7 0). Two studies suggested a reduction in attack rate in a physical training camp and a residential home for older adults ( 110, 7 7 7). In the 1918-1919 pandemic, excess death rates due to pneumonia and influenza decreased in New York City and Denver after isolation and quarantine were implemented ( 7 7 3).

Eleven simulation studies were conducted based on a wide range of assumptions, studying isolation as a single intervention or combined with other interventions. Six of the 11 studies predicted that implementation of case isolation would decrease the number of infections ( 7 02, 114-117, 119). In contrast, one study showed the difficulty in controlling influenza because of a potentially high proportion of asymptomatic transmission ( 7 04). Some studies predicted that isolation of sick individuals could delay the peak of an epidemic (116-118). One study predicted that isolation of 40% of cases would delay the epidemic peak by 83 days ( 116), while another predicted a similar effect, in which isolation of a reasonable proportion of cases would delay the arrival of the pandemic in countries globally (7 78). Although isolation alone was suggested to have a greater impact than other interventions, a combination of isolation and other interventions could further improve the effectiveness (102, 115, 117, 119).

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OVERALL RESULT OF EVIDENCE ON ISOLATION OF SICK INDIVIDUALS

1. Epidemiological and simulation studies suggested that isolation of sick individuals could reduce transmission in epidemics and pandemics. There is mechanistic plausibility for this intervention to be effective in reducing transmission.

2. The overall effectiveness of isolation is moderate, and combination with other interventions may improve the effectiveness.


Quality of evidence There is a very low overall quality of evidence that isolation of sick individuals has a substantial effect on transmission of influenza except in closed settings.

Values and preferences There could be variability in values and preferences among groups of people assigned to undergo isolation. Isolation can cause distress through fear and risk perceptions, especially when people face unclear information and communication during a disease outbreak (723). Many staff and contacts related to isolated patients may report social stigma and emotional strain due to loss of anonymity ( 124). Those who are not intimate with the patients, however, could consider isolation to be an effective intervention in reducing their own chances of being infected ( 123).

Balance of benefits and harms The objective of case isolation is to reduce transmission by reducing contact between ill persons and those who are susceptible (109). The overall effectiveness of isolation is moderate, and is greater when combined with other NPls. However, individuals who share a room with an isolated case (e.g. a family member or roommate) may be at a higher risk of infection, owing to increased contact ( 125).

Resource Implications The evidence for cost-benefit and cost-effectiveness of case isolation is limited across settings and all evaluation was qualitative rather than quantitative. A stochastic simulation model showed that encouraging voluntary isolation of patients is a more effective strategy than school closure. Case isolation is also relatively inexpensive compared with school closure ( 126). A model based on the population of Canada reported high cost-effectiveness with a combination of communitycontact reduction measures including personal protective measures, voluntary isolation and antiviral therapy ( 117). However, the cost-effectiveness of isolation alone was unclear. Direct costs might have a disproportionate impact on low-income groups, although the impact was considered moderate, and was mainly related to employment losses through people staying at home for 7-10 days ( 125, 7 27). Isolating patients may also increase the workload of health care workers or family members. The Implementation of case Isolation would Involve a relatively large amount of resources.

________________ r,n) WORLD HEALTH ORGANIZATION ~


Ethical considerations Implementation of isolation in general does not bring about many ethical concerns, because home isolation is often adopted voluntarily by individuals who do not feel well enough to work or engage in other daily activities ( 116, 119). Some ethical concerns may arise when isolation interventions are mandatory; the main concerns being freedom of movement ( 7 28) and social stigma ( 124). Although isolation is an important intervention, some individuals may face economic pressure to go to work rather than stay at home ( 7 29). Home isolation may also bring about increased risks of infection among household members. Older adults who live alone may not receive sufficient care and support when home isolation is implemented (88). Finally, although the evidence related to equity is limited, isolation could reduce the rate of infection in areas with poor sanitation and vulnerability, thereby increasing equity.

Acceptability Isolation of sick individuals is generally widely accepted by policy-makers and health workers, whereas the acceptability and compliance of case isolation among the public varies. A survey conducted among university students in the USA showed that at least 75% of people would like to isolate themselves from others when they are ill (130); however, only 6.4% of the cases remained at home (home isolation) ( 7 31). In a review, five studies reported that 50-96% of respondents intend to stay home rather than go to work when they are symptomatic; however, in another six studies the values reported were significantly lower (1-26%) ( 7 32). Family structure or the presumed infection status of family members can affect whether people accept isolation plans ( 702); for example, young children are less likely to be isolated alone at any stage of an epidemic ( 7 02).

Feasibility Isolation of sick individuals may not be feasible in certain circumstances, and there are some obstacles to isolation. Infected individuals who do not know of their infection status (e.g. pre-symptomatic or asymptomatic) could perpetuate transmission in the community (29). The effectiveness of case isolation is sensitive to the timing of response; however, such delay may be inevitable in some situations and will greatly reduce the effectiveness of this measure (7 78). In addition, ethical and social issues related to case isolation may contribute to the variable acceptability and compliance among the community.

r RECOMMENDATION:

Voluntary isolation at home of sick individuals with uncomplicated illness is recommended during all influenza epidemics and pandemics, with the exception of the individuals who need to seek medical attention. The duration of isolation depends on the severity of illness (usually 5-7 days) until major symptoms disappear.

Population: Infected cases



Quality of evidence


Most evidence was from simulation studies; four epidemiological studies are all considered as providing very low quality evidence. There is theoretical plausibility for isolation to be effective in reducing influenza transmission in the community.

CE NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA







Acceptability

Feasibility

Conditional

Conditional

Conditional

Conditional

Favourable

Conditional

Overall Recommended strength of recommendation

Values and preferences vary substantially among the community. Fear and social stigma are commonly experienced by patients and health care workers, while individuals who are not related to the isolated patients may consider case isolation to be an effective intervention in reducing their chances of being infected.

Home isolation could increase the risk of infection among family members.

Home isolation should not incur resources from the public sector but may be costly at a societal level. Isolation outside the home could be very costly.

Some ethical concerns arise when isolation measures are mandated, such as restriction of freedom of movement, lack of support for older adults who do not have a carer and economic pressure from work absenteeism.

Acceptability and compliance of isolation are variable, but generally at a moderate level.

This intervention may not be feasible because of many obstacles.

Home isolation of ill individuals is simple, feasible and likely to be acceptable in all influenza epidemics and pandemics. Isolation of ill individuals outside the home is unlikely to be feasible In most locations

Knowledge gaps: Most currently available studies on the effectiveness of isolation are simulation studies, which have a low strength of evidence. Available epidemiological studies looked at isolation combined with other interventions, or did not use laboratory-confirmed influenza as the outcome of interest. Although it is difficult to study isolation using RCTs, such studies would be very valuable. Understanding of transmission dynamics is incomplete, including the importance of pre-symptomatic contagiousness ( 7 33) and the fraction of infections that are asymptomatic ( 7 34). The optimum strategy for symptomatic persons is still uncertain.


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6.3. Quarantine of exposed individuals

Summary of evidence Terms relevant to isolation are defined below (Table 6).

Table 6. Definhion of terms relevant to quarantine

TERM DEFINITION

Quarantine Imposed separation or restriction of movement of persons who are exposed, who may or may not be infected but are not ill, and who may become infectious to others (709).

Household quarantine Confinement (commonly at home) of non-ill household contacts of a person with proven or suspected influenza (29, 709).

Home quarantine Home confinement of non-ill contacts of a person with proven or suspected influenza.

Self-quarantine Voluntary confinement of non-ill contacts of a person with proven or suspected influenza.

Work quarantine 1) Measures taken by workers who have been exposed and who

Maritime quarantine

Onboard quarantine

work in a setting where the disease is especially likely to transmit (or where there are people at higher risk from infection); for example, people working in homes for the elderly, and nurses in high-risk units (709).

2) Measures taken by health care workers who choose to stay away from their families when off duty, to avoid carrying the infection home (709).

Monitoring of all ship's passengers and crew for a defined period before permission is given to disembark( 7 35).

Monitoring of all flight's passengers and crew for a defined period before permission is given to disembark ( 7 36); this is also known as "airport quarantine" ( 7 36).

Six epidemiological studies (112, 135-139) and 10 simulation studies (702, 105, 114, 115, 117, 140-144) were eligible for inclusion in the review. Quarantine measures studied included household quarantine, border quarantine and maritime quarantine. Quarantine was studied as a single intervention or in combination with other interventions, generally with isolation and antiviral prophylaxis.

A quasi-RCT in Japan illustrated that voluntary waiting at home reduced risk of infection and number of infections (137). When a combination of isolation and quarantine was implemented in 1918-1919, excess death rates due to pneumonia and influenza were shown to decrease in New York City and Denver (112). Mandatory quarantine has also been shown to reduce the number of cases at the peak of epidemic fivefold, and it delayed the epidemic peak during the pandemic (H 1 N 1) 2009 in Beijing ( 139). Maritime quarantine in small island nations was reported to have delayed or prevented the arrival of the 1918-1919 pandemic, indirectly reducing mortality in the region (135). One study assessed onboard quarantine inspection and found a minimal

OJ NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


impact in detecting and preventing the entry of cases; however, following up with passengers thereafter was found to be effective in preventing secondary infection from travellers ( 7 36). An epidemiological study in Australia in 2009 found that the odds of a household contact who was currently quarantined with the index case-patient becoming a secondary case-patient increased for each additional day (adjusted odds ratio [OR]: 1.25, 95% Cl: 1.06-1.47) ( 7 38).

Among the simulation studies reviewed, four studies predicted a reduction in attack rate and cumulated incidence when quarantine of exposed individuals is implemented ( 7 02, 114, 115, 117). Combining quarantine with other interventions (e.g. household isolation with prophylaxis, school closure and workplace distancing) was suggested to further reduce influenza transmission (102, 114, 115). In addition, household quarantine has been suggested to be highly effective in reducing peak size and the total number of cases in a pandemic ( 7 44), whereas border quarantine had a minimal impact on reducing the number of cases (143). Three studies reported the effectiveness of household quarantine and border quarantine in delaying the epidemic peak ( 7 05, 117, 143). The combination with other interventions further improved the effectiveness of quarantine in delaying the epidemic peak ( 7 7 7).

If quarantine were to be implemented, a reasonable period of time would be 4 days after exposure, which covers two incubation periods of seasonal influenza. If data were available on the incubation period of a new pandemic strain, then the quarantine period could be adjusted accordingly.

r OVERALL RESULT OF EVIDENCE ON QUARANTINE OF EXPOSED INDIVIDUALS

1. The review identified six epidemiological studies and 10 simulation studies eligible for inclusion.

2. Quarantine is generally effective in reducing burden of disease and transmissibility, and in delaying the peak of the epidemic.

3. Some studies suggested a significant improvement in effectiveness of quarantine when combined with other interventions such as case isolation, antiviral prophylaxis or school closure.


Quality of evidence

_,J

There is a very low overall quality of evidence that quarantine of exposed individuals has an effect on transmission of influenza; the studies identified in the review reported or predicted variable effectiveness.

Values and preferences Values and preferences among quarantined populations are uncertain and variable. A survey in Turkey showed that a moderate percentage of students (69.4%) believed that quarantine was an effective intervention in reducing the transmission of influenza (145). The public expressed serious concerns for the potential outcomes of mandatory quarantine, such as overcrowding, exposure to infection, and inability to work, shop or contact family members (146, 147). Fear and a sense of

------------------------CE WORLD HEALTH ORGANIZATION


shame were also experienced by a proportion of the community, and many thought it impolite to maintain a distance from a sick acquaintance or relative ( 7 48). Health care workers were adversely affected due to the fear of acquiring infection ( 123). However, a study reported that 86.9% of the respondents held an optimistic attitude towards the effectiveness of quarantine ( 7 49).

Balance of benefits and harms The overall effectiveness of quarantine in reducing the burden of disease and delaying the peak of an epidemic is moderate. Quarantine may be particularly useful when antiviral drug resources are limited (725). However, the location of quarantine is an important factor in deciding whether the intervention will bring about any harm. During the influenza A(H 1 N 1 )pdm09 pandemic, a study from China reported that university students who were quarantined in the room with a confirmed case were at higher risk of illness ( 7 50). A quasi-cluster RCT reported similar results, finding that more home-quarantined individuals fell ill when there was a sick family member ( 7 37). The likelihood of a household contact who is concurrently quarantined with an isolated individual becoming a second case has been estimated to increase with each day of quarantine ( 7 38). Thus, family members who share the same room or facilities with the infected case may have an increased risk of acquiring influenza.

Resource implications Large-scale quarantine could be resource intensive. Household quarantine may be more costeffective in locations with limited capacity; however, enforcing quarantine or monitoring compliance could still be a challenge because of resource constraints.

Ethical considerations As with isolation, the main ethical concern of quarantine is freedom of movement of individuals ( 7 39). However, such concern is more significant for quarantine, because current evidence on the effectiveness of quarantine varies, and the measure involves restriction of movement of asymptomatic and mostly uninfected individuals. Mandatory quarantine increases such ethical concern considerably compared with voluntary quarantine ( 7 28). In addition, household quarantine can increase the risks of household members becoming infected ( 114, 137, 138). It has been suggested that a combined policy of household quarantine with antiviral prophylaxis can alleviate such concerns ( 7 7 4), but large stockpiles of antiviral drugs may not always be available for prophylactic use. Maritime quarantine and border quarantine are subject to similar concerns. On the other hand, onboard quarantine involves a shorter duration of restriction of movement, but current evidence suggests that this intervention has low cost-effectiveness and minimal impact on influenza control.

Acceptability Acceptability and compliance of quarantine are variable, but are generally at a moderate level ( 725). In a telephone survey conducted in Australia, more than 90% of respondents reported being willing to stay at home, especially after being given brief information about pandemic influenza (94.1% before and 97.5% after) (151). Two other studies had a similar conclusion, with 94% (752) and 92.8% ( 7 49) of respondents reported to adhere to a quarantine recommendation. However, a cross-sectional survey in Australia reported different results, with only 53% of households being fully compliant with quarantine. The compliance was better among individuals who had more understanding about quarantine (OR: 2.27) ( 7 53). Similar to the isolation of sick individuals, family structure or infection status of family members affects an individual's decision about whether to accept quarantine plans (702).



Feasibility There are some barriers and obstacles to the successful implementation of quarantine of exposed individuals. Home quarantine with infected cases can significantly increase the risk of acquiring infection ( 725). In addition, because the incubation period of a novel pandemic influenza strain may be uncertain, home quarantine may at times be implemented for an extended period, which will cause financial burden on families due to work absenteeism ( 154). There have been programmes of quarantine in 61 % of national pandemic plans, but detailed strategies of quarantine implementation were not provided and existing infrastructure may vary by country (65).

r RECOMMENDATION:

Home quarantine of exposed individuals to reduce transmission is not recommended because there is no obvious rationale for this measure, and there would be considerable difficulties in implementing it.

Population: People who have had contact with infected cases

When to apply: N/A


Quality of Very low The quality of evidence across all evidence {variable effectiveness) included articles, with the exception

of a quasi-cluster RCT, is very low. The effect of quarantine in reducing influenza transmission varied.

Values and Conditional There are likely to be concerns about preferences issues such as overcrowding, exposure to

infection and inability to contact family members when quarantine measures are implemented. However, most people should consider quarantine as a justifiable intervention.

Balance of Conditional The overall effectiveness in control of benefits and influenza is moderate; however, individuals harms subjected to quarantine with an infected

case could be at higher risk of acquiring infection.

Resource Conditional The evidence of cost-benefit or cost-implications effectiveness of quarantine measures is

limited, but the guideline development group believed that resources could be better used in other mitigation measures.

Ethical Conditional Individual freedom of movement and considerations the increased risk of infection among

individuals subjected to home quarantine with an infected case are essential ethical issues.



Cl


Acceptability

Feasibility


Favourable

Conditional

Not Recommended

Acceptability and compliance of quarantine varies, but are generally at a moderate level.

The feasibility of quarantine measures may not be high owing to the possible increase in secondary cases, and the financial burden due to work absenteeism.

Not recommended due to feasibility concerns with very low quality of evidence.

r ~

Knowledge gaps: Most of the currently available evidence on the effectiveness of quarantine on influenza control was drawn from simulation studies, which have a low strength of evidence. Available epidemiological studies did not rely fully on laboratory-confirmed influenza as the outcome of interest. Although it is difficult to study quarantine using RCTs, robust data from experimental studies would be valuable. In addition, as part of simulation studies, assumptions have been made in various aspects of model construction, many of which still require more robust evidence; for example, the asymptomatic fraction among all infections, the possibility of "superspreaders" and the nature of compliance behaviour (102, 141). There was limited information in the literature on the ideal or optimum timing of quarantine.

~ ~

N/A: not applicable; RCT: randomized controlled trial.

6.4. School measures and closures

Summary of evidence School-age children are particularly important in influenza transmission in the community, and attack rates are typically highest in this age group in epidemics and pandemics. School measures to reduce influenza transmission vary in scope from very simple measures (e.g. increasing distancing between desks) through to drastic measures (e.g. completely closing all schools). The systematic review team focused on school closures because this is the most well-studied measure; the team also examined evidence on other measures.

One published review examined school measures other than school closures, including increasing desk distance between students, cancelling or postponing after-school activities, restricting access to common areas, staggering the school schedule, reducing mixing during transport to and from school, dividing classes into smaller groups, and cancelling classes that bring students together from multiple classrooms (155). Another potentially important measure could be increasing attention to influenza-like symptoms in children, and either ensuring that ill children do not attend school or segregating them from other students.

cm NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA

APPENDIX TO JAMES CASCIANO DECLARATION-4-17

These measures could promote social distancing and decrease density among students, but there was limited evidence on the effectiveness of these measures ( 7 55).

Closure of schools can be reactive or proactive (Table 7) ( 7 56). Reactive closures occur when schools are closed after the occurrence of influenza outbreaks in those schools. Proactive closures occur when schools or groups of schools are closed as a deliberate measure to reduce transmission in the community, whether or not there have been influenza outbreaks in those schools. Class dismissal refers to the scenario where schools remain open but classes are not held; this can serve the purpose of continuing to provide school meals and childcare to some children (e.g. those from lower income families).

Table 7. Definition of terms relevant to school dosures

TERM

School closure

Class dismissal

Reactive closure or dismissal

Proactive closure or dismissal

Ill: influenza-like illness.

DEFINITION

School is closed to all children and staff.

School campus remains open with administrative staff, but most children stay home.

School is closed after a substantial incidence of Ill is reported among children or staff (or both) in that school.

School is closed before a substantial transmission among children and staff is reported.

A systematic review published in 2013 identified 79 epidemiological studies on school closures, and summarized the evidence as demonstrating that this intervention could reduce the transmission of pandemic and seasonal influenza among school children; however, the optimum strategy (e.g. length of closure, and whether it should be reactive or proactive) remained unclear, owing to heterogeneity of the data ( 157). The current systematic review updated the 2013 review, identifying 22 additional epidemiological studies that met the inclusion criteria, giving a total evidence base of 101 studies (Annex).

Included studies fell into a number of types. The first type of study involved the analysis of proactive school closures implemented in seasonal epidemics or in pandemics. A comprehensive analysis of interventions conducted in the USA in the 1918-1919 pandemic estimated that early and sustained interventions, including school closures, reduced overall mortality by up to 25% in some cities (758). Two other studies examined NPls in the 1918-1919 pandemic, and reported that the combined use of NPls (including school closures) was able to delay the time to peak mortality, and to reduce peak mortality and overall mortality ( 112, 159). Two studies conducted in Hong Kong SAR during the 2009 pandemic reported that a proactive 4-week school closure followed by scheduled school summer holidays reduced transmission in the community ( 160, 161), with one study estimating that the reproductive number was reduced from 1.7 to 1.5 during the proactive closures, and to 1.1 during the rest of the summer holidays ( 7 6 7). A study of school closures in Mongolia estimated a reduction in the overall attack rate by 1.1 % and a delay in the epidemic peak by more than 1 week ( 7 62).

A second group of studies investigated reactive school closures. One detailed study of transmission in a school in Pennsylvania identified no effect of the reactive closure that was implemented when 27% of students already had symptoms (763). Two studies conducted in Japan estimated reductions in the epidemic peak and overall attack rate by about 24% and 20% ( 164, 165). A study of reactive school closures in London in 2009 estimated that the closures reduced the reproductive number ________________ r,r,, WORLD HEALTH ORGANIZATION ~


from 1.33 (95% Cl: 1.11-1.56) to 0.43 (95% Cl: 0.35-0.52) (166). A study in the USA suggested that absenteeism could be reduced by about 2-3% after the reopening of school that had been closed due to outbreaks (167), and another study estimated that outbreak duration decreased by 4.98 days for a 2-day closure (768). However, other studies did not show a beneficial effect in reactive school closures in terms of reducing the overall attack rate and influenza duration ( 169, 7 70).

A third group of studies investigated the impact of regular school holidays. A study in France estimated that routine school holidays prevented 18% of seasonal influenza cases (18-21% in children) ( 177). Analysis of data from London from the 2009 pandemic suggested that transmission was substantially lower in the summer holidays of 2009, but resurged after schools reopened ( 7 72). An epidemiological analysis in Peru also reported that the number of infected cases declined throughout a school closure period (7 73). One study in the USA found an unchanged pattern in school-age children, but increasing influenza incidence among adults and children aged under 5 years during planned winter holidays (774). In addition, a cohort study in the USA indicated no difference in post-break absenteeism in schools on holidays compared with schools that remained open at the same time (RR: 1.07, 95% Cl: 0.96-1.20) ( 175). More recently, planned school holidays, including winter or summer holidays with the addition of some public holidays, were estimated to reduce influenza transmission ( 176-185) in terms of reducing transmission by 10-40% ( 176, 179-181, 185) and delaying the peak for more than 1 week ( 183, 184).

, OVERALL RESULT OF EVIDENCE ON SCHOOL MEASURES AND CLOSURES

1. The effect of reactive school closure in reducing influenza transmission varied but was generally limited. Proactive closures and planned school holidays had a moderate impact on transmission.

2. Although school closures alone might have an impact, combination with other interventions improved the effectiveness.

3. If schools remain open during a pandemic or epidemic, school measures can be considered in order to reduce transmission


Quality of evidence There is a very low overall quality of evidence, and the studies that have been published reported or predicted that school measures and closures have a variable effect on transmission of influenza.

Values and preferences There was little variability in the importance that populations assign to school closures; for example, in a survey in the USA, 92% of caregivers and 89% of teachers reported that they believed school closures were somewhat effective in reducing Influenza cases among school-age children (786). School closures affect families with children.



Balance of benefits and harms School closures can reduce influenza transmission, but the timing and duration is critical, and mistimed closures could lack impact. On the other hand, closures could have a major impact on the safety, health and nutrition of children in lower income families ( 7 87); for example, missing work to take care of children can affect income ( 7 25), and access to free school meals could be an additional concern for low-income families (788). School measures would reduce density and contact rates among students, and these interventions may cause mild disruption to schools and communities.

Resource Implications School closure is one of the measures that is found to be potentially not cost-effective ( 7 89). A review suggested that the cost of proactive closure can be significant, at £0.2 billion -£1.2 billion per week in the United Kingdom of Great Britain and Northern Ireland (which equates to 0.2-1 % of the United Kingdom's gross domestic product [GDP]), with similar results found in Australia ( 7 25). Proactive closure in the USA for 4 weeks could cost US$ 10-47 billion (0.1-0.3% of GDP) ( 7 90). Another study in the USA also estimated a $21 billion (> 3% GDP) loss for an 8-week reactive school closure ( 797). A simulation study predicted that school closures could reduce influenza transmission, but at increased cost to society ( 7 92). School measures could have some resource implications.

Ethical considerations School closures raise major ethical issues for families and communities ( 125, 188). Closures can have a substantial social impact because they may require parents to make other arrangements for care or supervision of their children, which can be particularly challenging for some families, especially if closures are prolonged. Social equity concerns might be exacerbated when closing schools, because children from lower income families may receive subsidized free food at school ( 7 88). Students' educational advancement could be jeopardized if they miss important exams or class work, and do not have alternative learning strategies (32). Moreover, media reporting of school closures may increase pandemic-related fears and concerns among the local community (32). Extending the school holidays might increase travel and thus lead to the temporary loss of health care workers from the health care system. Moreover, the availability of parents or caregivers would need to be taken into account when excluding ill children from school; segregation of ill children at school might be an alternative to exclusion in some locations.

Acceptability Two studies in the USA and Australia suggested that most families {more than 90%) agree to the implementation of school closure as a potential intervention to reduce influenza transmission ( 151, 193). To accommodate the closure period, the school may be required to extend the school year or offer alternative learning programmes (e.g. online learning), which may require extensive discussions with local authorities, given that extra costs may be incurred in extending the school year. There are also practical difficulties in communicating needs at different levels (national, local, school and individual), particularly in situations where uncertainty and risk assessments may change rapidly (194, 195). Such measures will probably only be acceptable to most stakeholders when the benefits clearly outweigh the negative consequences. According to a review of state government planning documents in the USA, in their published influenza preparedness for schools, 42% of the states mentioned that school measures could promote social distancing ( 7 55). The acceptability of school measures at a national level is likely to be high.



r

Feasibility The feasibility of school closure is questionable. Reactive school closures, rather than proactive school closures, are often implemented for operational reasons ( 794). Proactive school closures have been implemented during seasonal epidemics in some locations ( 7 94). School closures are most effective if children stay at home rather than engaging in extracurricular activities, although this may be difficult to control ( 196, 197). Most (61 %) national pandemic influenza preparedness implementation plans give recommendations about school closures but lack further detail (65). There may be considerable variation in social structures and legal frameworks relating to school closures in different Member States (198, 799). The guideline development group suggested that a class dismissal intervention could still include a provision for children of low-income families or essential workers to attend school, and this could be a more flexible measure than complete school closure.

RECOMMENDATION:

School measures (e.g. stricter exclusion policies for ill children, increasing desk spacing, reducing mixing between classes, and staggering recesses and lunchbreaks) are conditionally recommended, with gradation of interventions based on severity. Coordinated proactive school closures or class dismissals are suggested during a severe epidemic or pandemic. In such cases, the adverse effects on the community should be fully considered (e.g. family burden and economic considerations), and the timing and duration should be limited to a period that is judged to be optimal.

Population: Students and staff in childcare facilities and schools

When to apply: Gradation of interventions based on severity; school closure can be considered in severe epidemics and pandemics


Quality of Very low No RCTs were identified, and the quality of evidence (variable evidence is very low. The effect of school

1 effectiveness) measures and closures in reducing influenza transmission was variable.

~-·· - ·-~-~--~

Values and Favourable There was little variability in the importance preferences that populations assign to school closures.

Balance of benefits Conditional The balance between benefits and harms and harms is uncertain for school closures, which may

cause the loss of work or salary.

Resource Conditional School closures were associated with implications moderate costs but were less cost-effective

than stockpiling antiviral drugs or pre-pandemic vaccines.

Ethical I Conditional School closure has ethical repercussions considerations on families and communities, such as the

loss of subsidies for lower income families, and increasing fear and concern in the community (which may be exacerbated by heightened media attention).




Acceptability

Feasibility


Conditional

Conditional


Most families would accept the class dismissal decision, but the decisionmaking authority to close schools in different jurisdictions varies widely. School authorities may fear incurring extra costs by extending the school year. School measures are likely to be highly acceptable at a national level.

Because of the uncertainty and variability of influenza transmission, it is difficult to predict whether it will develop into a severe epidemic or pandemic.

School measures are likely to be feasible in any epidemic or pandemic. The balance between the advantages and disadvantages of school closures is less certain, but closure may be considered in more severe scenarios.

Knowledge gaps: More research is needed on the best triggers to close and reopen schools, and on the optimal timing and duration of school closures in order to maximize the impact of this disruptive intervention. The difference in compliance between individuals of different social status is still uncertain. There was little research on the impact of school measures on transmission.


6.5. Workplace measures and closures

Summary of evidence The systematic review identified 12 simulation studies and three epidemiological studies from the systematic review published by Ahmed et al. (200), and four additional studies from the updated search ( 117, 137,201,202). Workplace measures included paid-leave policy, telework from home, staggered shifts (e.g. having different activity and meal times, and times of entry and exit from the workplace), reduced contact and weekend extension. The epidemiological and simulation studies included in the review by Ahmed et al. suggested that these measures could reduce the overall number of influenza cases. In addition, the implementation of a workplace measure alone was associated with a median 23% reduction in the cumulative incidence of infections to a reproductive number of 1.9 or less (200). Simulation studies also showed a delay and reduction in the peak influenza attack rate; however, the effectiveness was estimated to decline with a higher basic reproductive number or a delay in implementation of the intervention (200).



Among the four most recent articles since the review by Ahmed et al., a quasi-cluster RCT in Japan showed that paid sick leave policy in the workplace reduced the overall risk of influenza A (Hl Nl) by about 20% in one influenza season ( 7 37). The other two epidemiological studies in the USA illustrated that providing paid sick leave could help to reduce transmission in workplaces resulting in an overall decrease of influenza-related absenteeism (207,202). Workplace measures combined with other interventions (e.g. school closures, personal protective measures and antiviral drugs) showed greater effectiveness ( 7 7 7).

Evidence on the effectiveness of workplace closure is limited; six simulation studies were identified (114, 142, 203-206). The simulation suggested that large-scale workplace closures could delay the time of peak occurrence for 5-10 days, but such closures were less effective than other interventions (e.g. school closures) (204,205). Closing all schools and closing 10% of workplaces could only delay the peak time by around 4% (206). Some studies predicted that workplace closures combined with school closures would be effective in reducing the spread of influenza by decreasing the overall attack rate by about 15-45% and decreasing the height of the epidemic peak by up to 40% (114,203,206). One simulation study predicted that the single strategy of workplace closure would have little impact; however, the combination of workplace closure, school closure, home isolation and a modest level of antiviral drug coverage would be effective in mitigating the impact of an epidemic ( 142).

OVERALL RESULT OF EVIDENCE ON WORKPLACE MEASURES AND CLOSURES

1. The included studies indicated that workplace measures (e.g. telework from home, staggered shifts, weekend extension and paid-leave policy) could reduce both the overall and the peak number of influenza cases, as well as delaying the occurrence ofthepeak.

2. The overall effectiveness and feasibility of workplace measures is modest, but combination with other interventions can improve its effectiveness.

3. The strength of evidence on workplace closure is very low because the identified studies are all simulation studies. Large-scale workplace closures could delay the epidemic peak for more than 1 week, and small-scale closures may have a modest impact on attack rate or peak number.

~ ~


Quality of evidence There is a very low overall quality of evidence that workplace measures and closures reduce influenza transmission.

Values and preferences There was uncertainty and variability in the importance that populations assign to workplace measures to reduce influenza transmission. A study in the Netherlands reported that 30% of respondents believed that staying home from work is an efficacious means of reducing influenza transmission (207); in another study, 93% of New York State residents believed that staying home is effective in preventing influenza transmission (208). A study in the USA showed that 28% of

mJ NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


employed respondents reported that they might lose their jobs or businesses as a result of having to stay home from work for 7-1 O days in the event of a pandemic influenza outbreak ( 127). This would also cause severe personal economic crises among some members of the public, but less so for those who received pay while they worked remotely ( 127).

Limited studies showed the values and perceptions among the population on the potential consequences of workplace closures. One study mentioned that large-scale workplace closures might raise the public's concern about the potential economic and financial consequences (209). Although there is limited evidence, it may be reasonable to expect increased levels of distress among employers and employees in the event of a workplace closure, because of possible operational and financial impacts (270).

Balance of benefits and harms Workplace measures could potentially reduce transmission by about 20-30%, based on the included studies. A review illustrated that telecommuting without pay would be inequitable, and would impact particularly on self-employed people or low-income families, because they have a higher risk of suffering from severe financial problems as a result of workplace measures ( 125). Large-scale workplace closures are likely to have substantial economic consequences. However, if school closures are also implemented, workplace closures may avoid the need for some working parents to make other childcare arrangements.

Resource implications The guideline development group believed that workplace measures and closures might be an economic burden on the government. Telecommuting was found to be modestly effective in reducing influenza transmission, but also likely to be economically disruptive ( 125). The most costly strategy considered in a simulation study was that of a continuous school closure together with a continuous 50% workplace non-attendance; this scenario has the highest overall cost (US$ 103 million) and the highest cost per prevented case (US$ 9894 per case) (211). Workplace closures can also be economically disruptive ( 125), and the cost of full workplace closures for any period of time will have significant economic impact (88).

Ethical considerations Workplace measures and closures could affect the economy and productivity of a society. A survey in the USA found that self-employed individuals and those unable to work from home might not be able to comply with recommended workplace measures because of job insecurity and financial considerations ( 125, 127). Social equity concerns may be exacerbated by workplace closure due to the lack of income to pay for necessities in lower income families.

Acceptability Workplace measures may be acceptable if they are well-planned in selected workplaces. Most stakeholders are unlikely to find workplace closures acceptable. The guideline development group encouraged giving isolated and quarantined individuals the opportunity to telework. Employees will accept workplace closures only if there is no anxiety regarding job security and income replacement (88). In addition, companies and authorities will not accept this intervention because of high operational costs.

Feasibility Telework, paid-leave policy and staggered-shift measures are unlikely to be feasible in most circumstances. Workplace closure is also likely to have a number of feasibility issues; for example, many companies provide essential services to the community or facilitate off-site working, and thus cannot be closed. Overall, the guideline development group believed that mandated workplace closure is unlikely to be feasible.



r

RECOMMENDATION:

Recommendation: Workplace measures (e.g. encouraging teleworking from home, staggering shifts, and loosening policies for sick leave and paid leave) are conditionally recommended, with gradation of interventions based on severity. Extreme measures such as workplace closures can be considered in extraordinarily severe pandemics in order to reduce transmission.

Population: Selected workplaces

When to apply: Gradation of interventions based on severity. Workplace closure should be a last step that is only considered in extraordinarily severe epidemics and pandemics


Quality of evidence





Acceptability

Feasibility

Very Low (effective)

Conditional

Conditional

Conditional

Conditional

Conditional

Conditional

One quasi-cluster RCT is on workplace measures, and the quality of the rest of the evidence is very low. All identified studies of workplace closure are simulation studies, which provide very low quality of evidence. Workplace measures and closures are effective in reducing influenza transmission in the community.

There is significant uncertainty surrounding people's values and preferences on workplace measures and closures.

Potentially effective in reducing influenza transmission, but may have economic harms.

Workplace measures and closures can be economically disruptive.

Workplace measures and closures may have adverse impacts on the economy and productivity of a society.

Unlikely to be acceptable in all but the most severe pandemics.

Many workplaces cannot be closed (e.g. those that provide essential services). Workplace closures may have limited feasibility.


APPENDIX TO JAMES CASCIANO DECL.ARA TION-425



The balance between the advantages and disadvantages of implementing workplace measures and closures is uncertain. Some measures may be relatively feasible and may contribute to reduced transmission in the community. Workplace closures may only be warranted as an extreme social distancing measure In an extraordinarily severe pandemic.

Knowledge gaps: As with school closures, more research is needed on the best trigger factors, timing and duration of workplace closures in order to maximize the impact of this highly disruptive intervention. There is a need for a comprehensive review of the ethical issues of workplace measures, as well as a comparison of the benefits and costs of implementing the measures. Other potential workplace measures have not been studied in depth, such as providing segregated working areas for people with mild symptoms. In addition, studies are needed on feasibility and scope of implementation of workplace measures, and the potential impact on families and the public.


6.6. Avoiding crowding

Summary of evidence Three epidemiological journal articles were included in our systematic review (112, 159, 212). One of those studies concerned World Youth Day 2008 pilgrims; it found that sleeping in a small group reduced the transmission of influenza compared with sleeping in one large hall (212). Another two articles were based on the 1918-1919 pandemic; both articles found that timely bans on public gatherings and closure of public places appeared to reduce the excess death rate (Spearman p=0.31 and 0.46) (112, 159). However, it is impossible to determine the individual effects of measures to avoid crowding in these studies.

r OVERALL RESULT OF EVIDENCE ON AVOIDING CROWDING

1. The effect of measures to avoid crowding alone in reducing transmission is uncertain.

2. Timely and sustained application of measures to avoid crowding may reduce influenza transmission, although the quality of evidence of its effectiveness is very low.




Quality of evidence There is a very low overall quality of evidence on whether avoiding crowding can reduce transmission of influenza.

Values and preferences There was uncertainty or variability in the importance that populations assign to avoiding crowding to reduce influenza transmission. A survey in Thailand reported that 54% of respondents believed that avoiding gatherings of five or more people could reduce the spread of diseases during an outbreak (2 7 3). Surveys in the United Kingdom and the Netherlands also showed a similar result: half of the respondents believed that this intervention would reduce the risk of getting infected with the influenza virus (87, 207).

There are differences in perception of expected outcomes from avoiding crowding among different populations. Some participants in a survey in the USA argued that they would approve of avoiding religious activities if it could reduce influenza transmission (209); however, other people believed that avoiding gatherings might prevent them from receiving support (e.g. worshipping and praying together) from their religious community during the crisis (209).

Balance of benefits and harms Avoiding crowding, in combination with other social distancing measures, may reduce influenza transmission, but there is no conclusive evidence to determine its effect (214). Modification, postponement or cancellation of mass gatherings may have cultural or religious implications, and may incur considerable costs (88, 209).

Resource implications The financial fragility of religious organizations was a concern, and mandatory closure may be seen as a financial hardship for many institutions (209). Governments might face legal liabilities for financial losses associated with workplace measures or closures.

Ethical considerations Avoiding crowding may have cultural or religious implications (209). Gatherings are important places to share information during influenza, which can comfort people and reduce fear. The abolition of religious gatherings may violate the devout faith of the participants and make them feel morally guilty. The guideline development group suggested that it would not be possible to cancel some events (e.g. the Hajj).

Acceptability The acceptability of avoiding crowding among the public may depend on the type and importance of the gathering ( 125). In a survey in Australia in 2007, 94.2% of participants were reported as being willing to avoid public events (757), and a polling study in five countries (Argentina, Japan, Mexico, United Kingdom and the USA) in 201 O showed that 11-69% of respondents would like to avoid places where many people gather (e.g. shopping centres or sporting events) during a pandemic (215). However, some participants might oppose the mandatory cancellation of religious gatherings during a pandemic (209). During a WHO consultation of influenza A(H 1 N 1 )pdm09, most reporting countries stated they had not instituted restrictions on mass gatherings, and were taking a wait-and-see approach for any upcoming events in their countries (216).

Feasibility There have been recommendations for the prohibition of mass gatherings but without further details in most (66%) national pandemic influenza preparedness implementation plans (65). However, it is still uncertain whether measures to avoid crowding alone would have a large effect.

~ NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK ANO IMPACT OF EPIDEMIC ANO PANDEMIC INFLUENZA


r

\.

RECOMMENDATION:

Avoiding crowding during moderate and severe epidemics and pandemics is conditionally recommended, with gradation of strategies linked with severity in order to increase the distance and reduce the density among populations.

Population: People who gather in crowded areas (e.g. large meetings, religious pilgrimages, national events and transportation hub locations).

When to apply: Moderate and severe epidemics and pandemics.


Quality of evidence




Very Low (unknown)

Conditional

Conditional

Conditional

Ethical ----~j Conditional consider~ions

Acceptability Conditional


No RCTs were found and the quality of evidence across all reviewed articles is very low. The effect of measures to avoid crowding alone is unknown.

Some people believe that the outcome of this intervention is conducive to reducing the risk of viral transmission, but others may view it as a barrier to accessing group support and personal freedom.

The effect of measures to avoid crowding alone is uncertain, and this intervention may have cultural or religious implications.

There might be cost considerations among organizers, attendees and employees.

There may be cultural or religious issues.

Likely to be acceptable in severe pandemics.

The programmatic considerations and existing infrastructure may hinder the implementation of avoiding crowding.

Overall Conditionally recommended

The balance between the advantages and disadvantages of avoiding crowding is less certain, but may be justifiable in severe pandemics.

strength of recommendation

Knowledge gaps: There are still major gaps in our understanding of person-to-person transmission dynamics. The reduction of mass gatherings is likely to reduce transmission in the community, but its potential effects are difficult to predict with accuracy. Large-scale RCTs

\. are unlikely to be feasible.


------------------------~ WORLD HEALTH ORGANIZATION ~


E! TRAVEL-RELATED MEASURES 7 .1. Travel advice

Summary of evidence There is no evidence measuring the effect of travel advice on influenza transmission.


Quality of evidence The quality of evidence cannot be judged because no study was identified.

Values and preferences Travel advice helps the public make informed decisions when travelling, and offers them an objective assessment of the risks involved in travelling during an epidemic or pandemic (217). Travel advice increases travellers' awareness of travel risk in affected regions. No literature on the values and preferences of travel advice was identified in the systematic review.

Balance of benefits and harms Travel advice can potentially reduce travellers' exposure to influenza viruses and limit the spread by deterring travel to regions affected by epidemics or pandemics (278). However, travel advice that recommends public avoidance of travel or trade may have financial consequences to the local and global economy (279). The systematic review did not identify any literature that demonstrated benefits and harms related to travel advice.

Resource implications The resource implications of providing information to individuals depend on the approach used to disseminate travel advice. However, the overall resource implications of providing travel advice are uncertain.

Ethical considerations Strategies to maintain public trust and increase compliance with the travel advice should be carefully considered (279).

Acceptability Public health authorities have generally included public awareness campaigns as part of their ongoing strategy to increase travellers' awareness of infectious disease risks, including influenza, during travel. Issues with acceptability of travel advice are unlikely, but cultural issues and potential economic consequences should be considered.

Feasibility Member States routinely provide travel advice for infectious diseases (e.g. dengue, malaria and Middle East respiratory syndrome), and they did provide advice in the early stages of the 2009 Hl Nl pandemic.

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RECOMMENDATION:

Travel advice is recommended for citizens before their travel as a public health intervention in order to avoid potential exposure to influenza and to reduce the spread of influenza.

Population: Citizens before travelling

When to apply: Early phase of pandemics


Quality of None No scientific evidence identified in the evidence systematic review.

i

Values and Favourable Travel advice can increase travellers' preferences awareness of travel risk in areas where they

may be exposed to circulating influenza viruses.

Balance of Favourable Although travel advice may contribute to benefits and the reduction of potential exposure and harms onward transmission of infections, there

may be economic consequences of reduced travel.

Resource Favourable Uncertain. May have consequences for implications countries affected early if travel advisories

are issued against those countries.

Ethical Favourable No major ethical issues. considerations

Acceptability Favourable Travel advice is likely to be acceptable in most settings.

Feasibility Favourable Travel advice is already used for other infections and in previous pandemics; there are no anticipated feasibility issues.

Overall Recommended No scientific evidence was Identified for strength of the effediveness of travel advice against-recommendation pandemic influenza; however, providing

information to travellers is simple, feasible and acceptable.

Knowledge gaps: Studies measuring the effect of travel advice on influenza transmission would be welcome.

~

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----------------F;fl WORLD HEALTH ORGANIZATION W


7 .2. Entry and exit screening

Summary of evidence Ten articles related to entry and exit screening were included in this review (785, 220-228). Observational studies conducted at airports estimated that the sensitivity of entry screening was low (226-228). Among arriving international travellers, half of the influenza cases were identified more than a day after arrival (through passive case finding and contact tracing in the community), although 37% of the influenza cases were screened while passing through the border entry site (185). Simulation studies estimated that screening international travellers may help to delay the epidemic by less than 2 weeks (0-12 days) (220-222).

OVERALL RESULT OF EVIDENCE ON ENTRY AND EXIT SCREENING

1. Ten studies were included in this review. 2. Considering the asymptomatic period of infected patients and

the sensitivity of screening devices, the effectiveness of screening travellers is likely to be very limited.


Quality of evidence There is a very low overall quality of evidence that entry and exit screening can delay the introduction of infection to a country and local transmission.

Values and preferences The sensitivity of screening can have an impact on the effectiveness of traveller screening at entry and exit points. Screening measures included health declarations, visual inspections and thermography to detect disease symptoms (229). One of the major criteria for screening travellers for influenza infections is fever, and screening sensitivity is largely reliant on detecting fever by available instruments. Infrared thermometers are used at some borders due to the instantaneous and non-invasive nature of their use. A study conducted in Japan during the influenza pandemic A(H1 N1 )pdm09 in 2009 reported that the sensitivity of infrared thermometers was 50.8-70.4% and the specificity 63.6-81.7% (224). A study conducted in New Zealand reported that the sensitivity of infrared thermal image scanners was 84-86% and the specificity 31-71 % (225). It is possible that some travellers with fever might opt to take antipyretics to reduce their symptoms before travel, to avoid detection of their fever by thermal scanners or thermometers.

Molecular diagnostics such as polymerase chain reaction {PCR) can be used at ports of entry, but these are generally more cost and resource intensive, and are unlikely to be applied to a large number of travellers (223). Point-of-care antigen detection tests might be more feasible but would also be costly (223).

Balance of benefits and harms The systematic review identified no literature on the harm of screening travellers. Influenza cases may remain asymptomatic for a few days {up to 2 days for seasonal influenza) { 7 85), symptom presentation varies and screening methods are imperfect (230); therefore, traveller screening for symptoms of influenza virus infection has major limitations in preventing the introduction of influenza into a location, and reducing the overall attack rate and duration of an epidemic (228).

DE NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA


Resource implications Substantial public health resources would be required, including adequate numbers of trained staff, screening devices and laboratory resources, and adequate infrastructure to conduct effective screening of travellers (228).

Ethical considerations Involuntary screening needs to be considered and implemented with care to respect the privacy of travellers (219).

Acceptability Screening travellers using infrared thermometers continues to be used in some ports of entry and is generally accepted by policy-makers as a uvisible" public health measure. Exit screening was not implemented in the 2009 influenza pandemic, and its acceptability for preventing or delaying the introduction of influenza infections to a location is uncertain.

Feaslblllty Entry screening is used in some ports of entry and has been shown to be feasible.

RECOMMENDATION:

Entry and exit screening for infection in travellers is not recommended, because of the lack of sensitivity of these measures in identifying infected but asymptomatic (i.e. presymptomatic) travellers.a

Population: N/ A

When to apply: N/ A


Quality of evidence




Very low (lack of effectiveness in reducing influenza transmission)

Conditional

Conditional

Conditional

The overall quality of available evidence was very low, and the overall effectiveness of entry and exit screening on influenza pandemics is ineffective due to the sensitivity of screening measures and asymptomatic period of infected patients.

One of the major criteria used in the screening of travellers for influenza infections is fever. Thus, screening sensitivity is largely reliant on the detection of fever.

There was no literature on the benefits and harms of traveller screening.

Substantial public health resources are required, which may be better used elsewhere.

_,J

11 Some locations routinely monitor the temperature of Incoming travellers; for example, In an effort to Identify Incoming travellers with symptoms of Ebola virus disease, avian influenza, Middle East respiratory syndrome or some other emerging Infectious disease. The recommendation here to not Implement entry or exit screening Is specific to seasonal and pandemic Influenza.

----------------F;rl WORLD HEALTH ORGANIZATION ~


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Ethical Conditional considerations

Acceptability Favourable

Feasibility Favourable

Overall Not Recommended strength of recommendation

Involuntary screening may have ethical or legal implications.

Screening is likely to be acceptable in general.

Feasibility has been demonstrated for several infectious diseases.

Not recommended due to the overall ineffectiveness in reducing the introdudion of infection and delaying local transmission.

Knowledge gaps: There were no high-quality studies on the effectiveness of entry and exit screening. Studies on the best approaches to screening travellers at different times, with different measures and for different pathogens are required to understand the potential advantages of screening travellers (230).

N/ A: not applicable.

7 .3. Internal travel restrictions This section covers internal travel restrictions only- international travel restrictions are not covered in this document1•

Summary of evidence One epidemiological study (23 7) and four simulation studies ( 114, 162, 232, 233) related to internal travel restrictions were included in this review. A time-series analysis study conducted in the USA showed that frequency of domestic airline travel is temporally associated with the rate of influenza spread, and following the September 11 attacks in 2001, a reduction in such travel delayed the epidemic peak by 13 days compared with the average for other years (23 7). A simulation study predicted that implementation of a strict travel restriction (95% travel restriction, enforced for 4 weeks) could reduce the epidemic peak by 12%, and a moderate restriction (50% travel restriction, enforced for 2-4 weeks) could delay the pandemic peak by 1-1.5 weeks (162). Another simulation study predicted that an internal travel restriction of more than 80% could be beneficial (232). A strict internal travel restriction (90%) was also consistently found to delay the epidemic peak by 2 weeks in the United Kingdom, and by less than 1 week in the USA (114). However, a 75% restriction had almost no effect ( 7 74).

r OVERALL RESULT OF EVIDENCE ON INTERNAL TRAVEL RESTRICTIONS

1. Five studies were included, four of which were simulation studies. 2. The effectiveness of internal travel restrictions depends on the level of

restriction - only very strict restrictions would be expected to have an impact on influenza transmission.

1 The WHO IHR secretariat Is In the process of developing a guidance on the effectiveness of travel and trade restrictions to prevent, delay or control international spread of diseases, lndudlng pandemic Influenza.




Quality of evidence There is a very low overall quality of evidence that internal travel restrictions can reduce influenza transmission.

Values and preferences Values and preferences related to internal travel restrictions are uncertain.

Balance of benefits and harms Legal and ethical issues surrounding restrictions on freedom of movement of persons (2 7 9) and economic consequences are potential harms that may result from internal travel restrictions (234).

Resource implications Restricting internal travel would require a large amount of public resources, including the provision of public advice and a large number of staff. Furthermore, there would be consequences for the supply chains of food and essential medicines due to the disruption of movement.

Ethical considerations The human right to freedom of movement should be considered (279), as should potential adverse economic impacts, particularly in vulnerable populations such as migrant workers and individuals who need to travel to seek medical attention (219).

Acceptability There is limited evidence for the effectiveness of internal travel restrictions, and it has legal, ethical and economic implications. Although 37% of national pandemic preparedness plans of Member States have travel restriction plans as a component of NPls (65), the acceptability is still undetermined.

Feasibility Some countries have already included travel restriction plans in their national pandemic preparedness plans. However, some countries cannot implement those plans because of their own laws. Therefore, travel restriction plans may be challenging to implement because of legal, ethical, economic and resource implications.

r

RECOMMENDATION:

Internal travel restrictions are conditionally recommended during an early stage of a localized and extraordinarily severe pandemic for a limited period of time. Before implementation, it is important to consider cost-effectiveness, acceptability and feasibility, as well as ethical and legal considerations in relation to this measure.


When to apply: Early phase of extraordinarily severe pandemics

----------------l:E WORLD HEALTH ORGANIZATION


FACTORS

Quality of evidence





Acceptability

Feasibility


ASSESSMENT


Conditional

Conditional

Conditional

Conditional

Conditional

Conditional


i

!

RATIONALE

The overall quality of the evidence was very low for the effectiveness of internal travel restrictions in an influenza epidemic or pandemic. Very strict internal travel restrictions are effective in reducing influenza transmission in the community.

Uncertain.

Internal travel restrictions can have important economic consequences. There is no published evidence of potential benefits, but theoretically transmission would be reduced.

Substantial implementation cost may be incurred.

The human rights of free movement should be considered, as should the adverse economic effects, particularly in vulnerable populations such as migrant workers and individuals who need to travel to access medical care.

Uncertain. . ---- -·--·-- . ·-~

Some countries already have travel restriction plans in place in the event of an epidemic or pandemic; however, some countries cannot implement these because of their own laws.

This measure can be conditionally recommended during the early stage of a localized extraordinarily severe pandemic for a limited period of time.

Knowledge gaps: No high-quality studies for the effectiveness of internal travel restrictions were identified. Studies to assess the effectiveness of internal travel restrictions and the costeffectiveness of this measure would be valuable to inform decisions on its use and to identify potential barriers to its implementation.

--~-·

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APPENDIX TO JAMES CASCIANO DECLARA TION-435

7 .4. Border closure

Summary of evidence Eleven articles related to border closure were included in the systematic review ( 7 7 4, 135, 204, 231, 235-239). Two were epidemiological studies (735,237) and nine were simulation studies (774,204, 234-240). An epidemiological study suggested an important influence of international air travel on the timing of influenza introduction (237). Another historical analysis of the 1918-1919 pandemic suggested that strict border control was a successful method for delaying and preventing influenza from arriving in South Pacific islands ( 7 35).

A simulation study predicted that 99% restriction of cross-border travel between Hong Kong SAR and mainland China may delay the epidemic peak by about 3.5 weeks compared with non-travel restriction (235). Another simulation study conducted in Italy predicted that international air travel restriction would delay the peak of epidemic by about 1-3 weeks, depending on the transmission rate and the level of restriction (204). However, the attack rate was not significantly affected (204). Furthermore, simulation studies based on a global scale model also predicted that international travel restriction would delay epidemics by about 2-3 weeks (236) and significantly delay its global spread (5-133 days) (23n. Strict border control of 99.9% may be effective in delaying the epidemic peak by 6 weeks, while 90% and 99% border control would delay the epidemic peak by 1.5 and 3 weeks, respectively ( 7 7 4). International travel restriction is estimated to slow the importation of infections (234,238), but would not reduce the epidemic duration (238). Because the supply of essential items to a population, such as food and medical supplies, often relies on importation, strict border closures need to be carefully considered before implementation in island countries and territories (239).

r OVERALL RESULT OF EVIDENCE ON BORDER CLOSURE

1. Eleven studies were Included in this review. 2. Generally, only strict border closures are expected to be effective

within small island nations. 3. For island nations, border closure should be carefully considered

because it may affect the supply of essential items to the population.


Quality of evidence There is a very low overall quality of evidence that border closure has an effect on transmission of influenza, and studies in the literature reported or predicted variable effectiveness.

Values and preferences Values and preferences related to border closure are uncertain.

Balance of benefits and harms No scientific evidence of the harm of border closure for individuals was identified. However, it is reasonable to expect that strict border control could affect daily life and have serious economic consequences.

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----------------~ WORLD HEALTH ORGANIZATION lt:,,l.t


Resource implications No costing studies on border closure were identified; however, the cost will be prohibitive in most countries because of the closure of borders (air, land and sea). Substantial public resources would be needed, including the provision of public advice and large numbers of staff to restrict crossborder travel. Furthermore, there would be consequences for the supply chain for food and essential medicines, as well as broader economic consequences.

Ethical considerations The right to free movement of persons should be considered (2 7 9). As with internal travel restrictions, border closure applied by nations should be done voluntarily as much as possible, and compulsory intervention should be involved as a last resort (219). Furthermore, the stigmatization and discrimination of individuals from affected areas and economic impacts of border closures should also be carefully considered (279,247).

Acceptability There is limited evidence for the effectiveness of border closures, and it has legal, ethical and economic implications.

Feasibility Border closure in severe pandemics is technically feasible, and it may be most effective if implemented in the very early phase of a pandemic. However, the above-mentioned ethical, economic and resource implications affect its feasibility.

RECOMMENDATION:

Border closure is generally not recommended unless required by national law in extraordinary circumstances during a severe pandemic, and countries implementing this measure should notify WHO as required by the IHR (2005).

Population: General Public

When to apply: N/ A


Quality of evidence Very low The overall quality of evidence for the (variable effectiveness of border closure was very effectiveness) low. The effect of border closure in reducing

influenza transmission is varied. I

Values and Conditional Uncertain. preferences

Balance of benefits Conditional May be effective in delaying importation of and harms new cases but at major economic cost.

·-

Resource Conditional A large amount of public resources would implications be needed and there would be considerable

economic consequences.

Ethical Conditional Ethical issues relating to restrictions of free considerations movement should be carefully considered.

--

m: NON-PHARMACEUTICAL PUBLIC HEALTH MEASURES FOR MITIGATING THE RISK AND IMPACT OF EPIDEMIC AND PANDEMIC INFLUENZA



Acceptability Conditional


Overall Not Recommended strength of recommendation

There is limited evidence for the effectiveness of border closure, and it has legal, ethical and economic consequences. However, the acceptability is still unclear.

Likely not to be feasible in most locations.

Overall, border closure is not recommended unless required by national law or in extraordinary circumstances during a severe pandemic, and countries should notify WHO as required by IHR. This is due to the very low quality of evidence, economic consequences, resource Implications and ethical implications.

Knowledge gaps: Due to the lack of high-quality evidence, the benefit of border closure is still uncertain (237). Cost-benefit studies to assess the advantages and disadvantages of border closure are needed.

IHR: International Health Regulations; N/ A: not applicable; WHO: World Health Organization.



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