Severe Acute Respiratory Syndrome (SARS)

嚴重急性呼吸道症候群

陳宜君醫師臺大醫院內科部

SARS

SARS 是世界衛生組織 (WHO) 在 2003 年 3 月 15 日新公布的名稱，在這之前稱為非典型肺炎。

SARS 流行事件開始於 2003 年 2 月 26 日越南河內的一位美國商人發病就醫，後來送香港治療後死亡。之後在香港、越南陸續出現非典型肺炎合併有呼吸道感染症狀的案例。

其特點為發生瀰漫性肺炎及呼吸衰竭，較過去所知病毒、細菌引起的非典型肺炎嚴重，因此取名為嚴重急性呼吸道症候群 (Severe Acute Respiratory Syndrome, SARS)

與時間賽跑 SARS 的全球疫情3 月 12 日，世界衛生組織針對 SARS 提出全球警訊3 月 14 日，美國疾病管制局啟動緊急醫療中心，並

派出專家至亞洲國家協助世界衛生組織進行疫情調查。3 月 14 日，台大醫院通報國內第一、二例 SARS 極

可能病例。第一例是境外移入的指標病例，第二例是家族內傳播的第一例本土病例。

3 月 5 日，加拿大多倫多第一例 SARS 病例死亡。自 2003 年 2 月 1 日起兩個月內，已經超過 1800 人

被診斷 SARS ，分佈在 17 個國家。

WHO 5/8/2003

Country/ Cumulative # of # of Date last area # of cases death recovered probable case

reported

China 4698 224 1529 8/May/2003Hong Kong 1661 208 1008 8/May/2003Taiwan 131 13 26 8/May/2003 Singapore 204 27 153 5/May/2003

Total 7053 506 2959

Case Definitions for Surveillance of SARS WHO 5/1/2003

Objective To describe the epidemiology of SARS and to monitor the magnitude and the spread of this disease, in order to provide advice on prevention and control

Introduction The surveillance case definitions based on available clinical and epidemiological data are now being supplemented by a number of laboratory tests and will continue to be reviewed as tests currently used in research settings become more widely available as diagnostic tests.

Introduction (cont.) Preliminary clinical description of Severe Acute Respiratory Syndrome summarizes what is currently known about the clinical features of SARS.

Countries may need to adapt case definitions depending on their own disease situation.

Retrospective surveillance is not expected.

Case Definitions for Surveillance of SARS Suspect case WHO 5/1/2003

1.   A person presenting after 11/1/2002 with history of: -  high fever (>38C) AND -  cough or breathing difficulty AND

one or more of the following exposures during the 10 days prior to onset of symptoms: -  close contact with a person who is a suspect or probable case of SARS; -  history of travel, to an area with recent local transmission of SARS-  residing in an area with recent local transmission of SARS

Case Definitions for Surveillance of SARS

Suspect case WHO

5/1/2003

2.  A person with an unexplained acute respiratory illness resulting in death after 11/1/2002, but on whom no autopsy has been performed AND one or more of the following exposures during to 10 days prior to onset of symptoms: -  close contact, with a person who is a suspect or probable case of SARS; -   history of travel to an area with recent local transmission of SARS-  residing in an area with recent local transmission of SARS

Case Definitions for Surveillance of SARS

Probable case WHO

5/1/2003

1. A suspect case with radiographic evidence of infiltrates consistent with pneumonia or respiratory distress syndrome (RDS) on chest X-ray.

2. A suspect case of SARS that is positive for SARS coronavirus by one or more assays.

3. A suspect case with autopsy findings consistent with the pathology of RDS without an identifiable cause.

Case Definitions for Surveillance of SARS WHO 5/1/2003

Exclusion criteria A case should be excluded if an alternative diagnosis can fully explain their illness.

Reclassification of cases

Case Definitions for Surveillance of SARS

Reclassification of cases WHO

5/1/2003

As SARS is currently a diagnosis of exclusion, the status of a reported case may change over time.

A patient should always be managed as clinically appropriate, regardless of their case status.

A case initially classified as suspect or probable, for whom an alternative diagnosis can fully explain the illness, should be discarded after carefully considering the possibility of co-infection.

Case Definitions for Surveillance of SARS

Reclassification of cases WHO

5/1/2003

A suspect case who, after investigation, fulfils the probable case definition should be reclassified as "probable".

A suspect case with a normal CXR should be treated, as deemed appropriate, and monitored for 7 days. Those cases in whom recovery is inadequate should be re-evaluated by CXR.

Those suspect cases in whom recovery is adequate but whose illness cannot be fully explained by an alternative diagnosis should remain as "suspect".

Case Definitions for Surveillance of SARS

Reclassification of cases WHO 5/1/2003

A suspect case who dies, on whom no autopsy is conducted, should remain classified as "suspect".

If this case is identified as being part of a chain transmission of SARS, the case should be reclassified as "probable".

If an autopsy is conducted and no pathological evidence of RDS is found, the case should be "discarded".

Case Definitions for Surveillance of SARS WHO 5/1/2003

The surveillance period begins on 11/1/2002 to capture cases of atypical pneumonia in China now recognized as SARS. International transmission of SARS was first reported in March 2003 for cases with onset in February 2003.

Close contact: having cared for, lived with, or had direct contact with respiratory secretions or body fluids of a suspect or probable case of SARS.

Reporting procedures - All probable SARS cases should be managed in the same way for the purposes of infection control and outbreak containment

At this time, WHO is maintaining surveillance for clinically apparent cases only ie probable and suspect cases of SARS.

Testing of clinically well contacts of probable or suspect SARS cases and community based serological surveys are being conducted as part of epidemiological studies which may ultimately change our understanding of SARS transmission. However, persons who test SARS CoV positive in these studies will not be notified as SARS cases to WHO at this time.

Case Definitions for Surveillance of SARS WHO 5/1/2003

Where laboratory tests are not available or not done, probable SARS cases as currently defined above should continue to be reported in the agreed format.

Suspect cases with positive laboratory results will be reclassified as probable cases for notification purposes only if the testing laboratories use appropriate quality control procedures.

Case Definitions for Surveillance of SARS WHO 5/1/2003

No distinction will be made between probable cases with or without a positive laboratory result and suspect cases with a positive result for the purposes of global surveillance.

WHO will negotiate sentinel surveillance of SARS with selected partners to collect detailed epidemiological, laboratory and clinical data.

Cases that meet the surveillance case definition for SARS should not be discarded on the basis of negative laboratory tests at this time.

Case Definitions for Surveillance of SARS WHO 5/1/2003

Rationale for retaining the current surveillance case definitions for SARS WHO 5/1/2003

The reason for retaining the clinical and epidemiological basis for the case definitions is that at present there is no validated, widely and consistently available test for infection with the SARS coronavirus.

Antibody tests may not become positive for three or more weeks after the onset of symptoms. We do not yet know if all patients will mount an antibody response.

Rationale for retaining the current surveillance case definitions for SARS WHO 5/1/2003

Molecular assays must be performed using appropriate reagents and controls under strictly controlled conditions, and may not be positive in the early stages of illness using currently available reagents.

We are not yet able to define the optimal specimen to be tested at any given stage of the illness.

This information is accruing as more tests are being performed on patients with known exposures and/or accompanied by good clinical and epidemiological information. We hope that in the near future an accessible and validated diagnostic assay(s) will become available which can be employed with confidence at a defined, early stage of the illness.

SARS 的潛伏期通常為 2 至 7 天，但也可能長達 10 天。

疾病通常先以發燒為前趨症狀（ >38℃），通常為高溫，有時會發冷及寒顫；

有時尚伴隨著其他症狀包括頭痛、倦怠及肌肉痛。有些病人發病時會產生輕微的呼吸道症狀。雖然有部份病人在發燒時會發生腹瀉，但通常並不會有皮疹及神經或腸胃道症狀。

SARS 臨床症狀

SARS 臨床症狀

3 至 7 天後進入下呼吸道期（ lower respiratory phase ），開始沒有痰的乾咳，或因呼吸困難而導致血氧過低。

有 10-20% 的病人，呼吸道疾患嚴重到必須插管及使用呼吸器。

合乎目前世界衛生組織 SARS 極可能（ probable ）及疑似病例定義者之致死率約為 3% 。

SARS胸部 X光攝影

在發燒前驅症狀，甚至整個病程，胸部 X光攝影可能正常。

不過在大部份的病患，呼吸道時期（ respiratory phase ）的特性為從早期的局部（ focal ）浸潤，進展到較廣泛性、斑狀（ patchy ）、間質性浸潤，

有些 SARS晚期病人的胸部 X光攝影可見部份區域實質化（ consolidation ）。

傳播方式

飛沫傳染：近距離、反覆接觸。

空氣傳染

口糞傳播： 有些動物的糞便可培養出冠狀病毒

許多台大的病人初期有腹瀉

Vector-borne： fomites ，因為冠狀病毒可在環境中生存數小時之久。

A Hospital Outbreak of Severe Acute Respiratory Syndrome in Hong Kong

Lee et al., www.nejm.org April 7, 2003

From March 11 to 25, 2003, a total of 156 patients were hospitalized with SARS at the Prince of Wales Hospital

138 cases were identified as having either secondary or tertiary cases and were admitted to the isolation wards of

Clinical features

Symptoms: fever (100%); chills, rigors, or both (73.2%); myalgia

(60.9%) cough (57.3%), headache (55.8%), dizziness (42.8%); sputum production (29.0), sore throat (23.2%), coryz

a (22.5%), nausea & vomiting (19.6%), diarrhea (19.6%)

Physical findings on admission: fever 38.4C (35~40.3C), inspiratory crackles at the base of the lung

Laboratory findings

lymphopenia (69.6%) thrombocytopenia (44.8%) elevated lactase dehydrogenase (71.0%) creatine kinase levels (32.1%)

CXR

At the onset of fever, 78.3% had abnormal CXR, all showed air-space consolidation, indistinguishable f

rom those associated with other causes of bronchopneumonia, peripheral- zone involvement predominant

unilateral focal involvement (54.6%), unilateral multifocal or bilateral involvement (45.4%)

Thoracic CT: Peripheral air-space consolidation, similar to those found in bronchiolitis obliterans organizing pneumonia

Prospective study of the clinical progression of SARS in a community outbreak

The fever and pneumonia initially responded to treatment.

However, patients developed recurrent fever (85.3%) on day 8.9 ± 3.1 (range 4 to 18), watery diarrhoea (73.3%) on day 7.5 ± 2.3 (range 3 to 15), radiological deterioration (80%) on day 7.4 ± 2.2 (range 3 to 13) and respiratory deterioration (45.3%) on day 8.6 ± 3 days (range 5 to 19).

Peiris et al., and members of the HKU / UCH SARS Study Group. Lancet 2003

Prospective study of the clinical progression of SARS in a community outbreak

In 45.3% of patients, marked improvement of initial pulmonary lesions was closely associated with appearance of new radiological lesions at other sites.

20% progressed to acute respiratory distress syndrome (ARDS) during the third week.

Age and chronic HBV infection are independent significant risk factors for progression to ARDS on multivariate analysis.

Subsequent analysis of clinical specimen of 20 patients with initial NPA RT-PCR positive and antibody seroconversion to SARS associated coronavirus

Day after 10 13 16 19 21onset

NPA (positivity rate) 95% 90% 90% 75% 47.4%

Stool (positivity rate) 100% 100% 95% 80% 66.7%

Urine (positivity rate) 50% 45% 35% 30% 21.1%

Clinical progression and viral load of SARS associated coronavirus pneumonia

Quantitative RT-PCR of nasopharyngeal aspirates in 14 patients (4 had ARDS and 10 without ARDS) consistently demonstrated a peak viral load at day 10 and a decrease to admission level at day 15.

Faecal excretion of coronavirus was present and continued through the period of follow-up.

Seroconversion and RT-PCR of nasopharyngeal aspirates and stool are useful for confirmation of SARS.

Interpretation:

The consistent clinical progression, shifting radiological infiltrates and an inverted V viral load profile suggested that deterioration during the second week is not related to uncontrolled viral replication but may rather be related to immunopathological damage.

Incubation period 潛伏期 Incubation period: Intervals between exposure to the

index patient or ward and the onset of fever SARS

Tsang et al., NEJM, Mar 31, 2003: 2-11 days Lee et al. NEJM, Apr 7, 2003: 2~16 days (median, 6

days) Common atypical pneumonia

Mycoplasma pneumoniae: 6-32 天（ 14 天）Clamydia pneumoniae: 10-30 天Leginella pneumoniae: 不會人傳給人

Incubation period WHO 5/7/2003

WHO has also reviewed estimates of the incubation period of SARS, using individual case data.

On the basis of this review, WHO continues to conclude that the current best estimate of the maximum incubation period is 10 days.

The incubation period can vary from one case to another according to the route by which the person was exposed, the dose of virus received, and other factors, including immune status.

The incubation period, which is the time from exposure to a causative agent to onset of disease, is particularly important as it forms the basis for many recommended control measures, including contact tracing and the duration of home isolation for contacts of probable SARS cases.

Knowledge about the incubation period can also help physicians make diagnostic decisions about whether the presenting symptoms and clinical history of a patient point to SARS or to some other disease.

Prompt isolation WHO 5/7/2003

WHO continues to recommend the earliest possible isolation of all suspect and probable cases of SARS. A short time between onset of symptoms and isolation reduces opportunities for transmission to others.

It also reduces the number of contacts requiring active follow-up, and thus helps relieve some of the burden on health services. In addition, prompt hospitalization gives patients the best chance of receiving possibly life-saving care should their condition take a critical course.

A comparison of the courses of common-source and propagated epidemics

High infectivity of SARS agent 112 secondary cases:

69 health care workers and 16 medical students, who were work in the index ward;

54 patients who were either in the same ward or had visited their relatives there

26 tertiary cases: family members of the infected HCWs

Transmission by droplets and possibly by fomites were suspected.

High infectivity of SARS agent

The use of a jet nebulizer to administer aerosolized albuterol in the index patient had probably aggravated the spread of the disease by droplet infections.

Airborne precautions and contact precautions were instituted therefore, as recommended by the CDC.

Course and outcome

23.2% were admitted to ICU 13.8% required mechanical ventilation 5 of 138 patients died, all of whom had coexisting con

ditions.

Lee et al., www.nejm.org April 7, 2003

Independent predictors of an adverse outcome

advanced age (OR per decade of life, 1.80; 95% CI, 1.16 to 2.81; P=0.009)

high peak lactate dehydrogenase level (OR per 100 U per liter, 2.09; 95%CI, 1.28 to 3.42; P=0.003)

high absolute neutrophil count on presentation (OR, 1.60; 95%CI, 1.03 to 2.50; P=0.04).

Lee et al., www.nejm.org April 7, 2003

SARS case fatality ratio 5/7/2003 Case fatality ratio

WHO has today revised its initial estimates of the case fatality ratio of SARS. The revision is based on an analysis of the latest data from Canada, China, Hong Kong SAR, Singapore, and Viet Nam.

On the basis of more detailed and complete data, and more reliable methods, WHO now estimates that the case fatality ratio of SARS ranges from 0% to 50% depending on the age group affected, with an overall estimate of case fatality of 14% to 15%.

The likelihood of dying from SARS in a given area has been shown to depend on the profile of the cases, including the age group most affected and the presence of underlying disease.

Based on data received by WHO to date, the case fatality ratio is estimated to be

< 1% < 24 years

6% 25 to 44 years

15% 45 to 64 years

> 50% 65 years

Tsang et al., NEJM 3/31/2003

Tsang et al., NEJM 3/31/2003

Poutanen et al. NEJM 3/31//2003

Poutanen et al. NEJM 3/31//2003

SARS 致病菌

2003 年 3 月 24 日美國疾病管制局及香港專家，宣布分離出一種冠狀病毒 (coronavirus) 。

目前正針對已知的冠狀病毒 polymerase基因的核酸序列比對，發現與已知的人類病毒不同。

數個病人的急性期及恢復期血清顯示有血清陽轉(seroconversion) 。

支持冠狀病毒是 SARS 致病菌的證據

組織培養 電子顯微鏡 Microarray 技術 間接免疫螢光染色 聚合脢鏈反應 (polymerase chain reaction)

SARS “super-spreaders”

“Super-spreader” is a term that has been used to describe certain individuals with atypical pneumonia, now recognized as cases of SARS, who have been implicated in spreading the disease to numerous other individuals.

SARS “super-spreaders”

In SARS outbreaks, a “super-spreader” is a source case who has, for as yet unknown reasons, infected a large number of persons.

It remains unknown whether such “super-spreaders” are persons secreting an exceptionally high amount of infectious material or whether some other factor, perhaps in the environment, is working to amplify transmission at some key phase of virus shedding.

The phenomenon of a “super-spreader”, which is not a recognized medical condition, dates back to the early days of the outbreak. At that time, when SARS was just becoming known as a severe new disease, many patients were thought to be suffering from atypical pneumonia having another cause, and were therefore not treated as special cases requiring special precautions of isolation and infection control.

As a result, stringent infection control measures were not in place. In the absence of protective measures, many health care workers, relatives, and hospital visitors were exposed to the SARS virus and subsequently developed SARS.

Since infection control measures have been put in place, the number of new cases of SARS arising from a single SARS source case has been significantly reduced.

When investigating current chains of continuing transmission, it is important to look for points in the history of case detection and patient management when procedures for infection control may have broken down.

對 SARS 疫情的反應

科學界快速的新發現，以及國際間溝通的速度及效率是對 SARS反應的特點，反映出科學、科技及國際合作的無比成就。

但是，亞洲部份地區的疫情持續擴散，家屬人員及醫療人員的高罹病率 (attack rate)顯示該菌是高傳染性的。

香港旅館內及社區內的傳播顯示 SARS 的致病菌的傳播相當有效率。此外，飛機內傳播也被證實了。

Gerberding JL, CDC, NEJM, April 2, 2003

控制疫情─悲觀面

迄今尚無成功的預防呼吸道病毒感染的 population-based strategy 。

即使流行感冒病毒已有有效的疫苗，每年的感染率及相關死亡率仍居高不下。

假如 SARS 傳播模式與流行性感冒病毒相同，而且沒有疫苗、預防及治療藥物，則疫情的控制將非常困難。

Gerberding JL, CDC, NEJM, April 2, 2003

控制疫情─樂觀面

動物感染冠狀病毒已有疫苗可預防。

快速篩選以上市或發展中的抗病毒藥物（進行中）

隔離措施及疫情監控。

季節變遷（樂觀期望 ) 。

Gerberding JL, CDC, NEJM, April 2, 2003

Drazen JM (editorial). NEJM. Mar 31, 2003

我們都希望這個疫情將很快結束，但只依賴希望是愚蠢的。

送給醫療人員的座右銘是「小心」，而不是「恐慌」。

對 SARS相關表徵提高警覺。 面對 SARS疑似病例時遵循WHO 及 CDC 的建議。 隨時上網瞭解新的資訊及進展。

Concept

Treating sepsis - PIRO

Predisposing factors

Infection

Response

Organ dysfunction

Vincent JL. Lancet 2002;2:135

Treatment protocol 3/17/2003

General principlesAntiviral therapy: ribavirin (IV, inhalation, oral)Respiratory care Anti-inflammatory agent: steroid (prednisolon

e 2 mg/kg/day)Immunomodulating agent: IVIG (1 gm/kg/day

for 2 days)

General principles

Empiric therapy should include coverage for organisms associated with any community-acquired pneumonia of unclear etiology, including agents with activity against both typical and atypical respiratory pathogens.

Treatment choices may be influence by severity of the illness.

Infectious disease and chest consultation is recommended.

Ribavirin inhalation therapy for patients with respiratory failure

Dosage: 60mg/cc x 20cc (1.2g) inhalation for 2 hr q8h for 5~7 days

Candidate: patients with mechanical ventilation (to avoid environmental exposure of caregivers to the drug

Chakrabarti et al. Pre-emptive oral ribavirin therapy of paramyxovirus infections after haematopoietic stem cell transplantation: a pilot study. Bone Marrow Transplantation 2001;28:759-63.

Ribavirin inhalation therapyViratec small particle aerosol generator (SPAG-2)

IV Ribavirin

Dosage: 33mg/kg IV （ max. 2g ） loading dose then, 16mg/kg IV （ max. 1g ） q6hr for 4 days, 8 mg/kg IV (max. 0.5g) q8hr for 3 ~6 days depending on clinical response & tolerance The doses are infused intravenously over 30 min. Candidate: severe infection and intolerance to oral agent Side effects: bradycardia and other cardiotoxicity

Oral ribavirin: candidate Probable SARS

Close contact to patients hospitalized due to probable SARS

Fever (>38 ° C) and abnormal CXR Suspect SARS, high probability

Unexplained fever (>38°C) 3 days & normal CXR Close contact to patients hospitalized due to pro

bable SARS Myalgia, diarrhea, normal WBC, elevated CRP, a

bnormal GOT/GPT/CPK, etc.

Oral ribavirin Dosage: 2000 mg loading dose then, 600 mg bid (weight > 75 kg) or 1000mg/day (400 mg & 600 mg bid; weight 75 kg or less) for 10 days.

The patients were prescribed the nearest rounded dose of 200 mg capsules and were advised to take the drug with food.

Patients were advised to undertake contraceptive precautions for 6 months after cessation of ribavirin therapy

Adverse reaction: Inhalation Ribavirin

1~10%: fatigue, headache, insomnia, nausea, anorexiaanemia

< 1%hypotension, cardiac arrest, digitalis toxicity, mild bronchospasm, worsening of respiratory func

tion, apneaconjunctivitisBradycardia

Adverse reactionoral ribavarin + Interferon -2b for 48 wks

insomnia 35%/24%, irritability 25%/19%

nausea 34%/23%, anorexia 22%/16%, dyspepsia 11%/9%,

rash 19%/6%, pruritus 21%/9%

dyspnea 13%/8%

anemia 15%, neutropenia 9%/6%,

Respiratory care for SARSOxygen therapy

Indicated for patients with SpO2 < 95% or PaO2 < 80 mmHg when breathing room air

Maintain SpO2 > 90% or PaO2 > 60 mmHg (by nasal cannula, non-rebreathing mask),

Simple O2 mask is NOT recommended for SARS. Avoid nebulizer or nebulized aerosol medication thro

ughout the treatment course.

Indication for intubation

1. Absolute indication: PaO2/FiO2 < 150 mmHg , or non-rebreathing mask PaO2 < 100 mmHg)

2. Relative indication: PaO2 < 200 mmHg or PaCO2 > 50 mmHg or pH < 7.25 (due to respiratory acidosis)

# Note: (1) Non-invasive ventilation (BiPAP, CPAP, NIPPV) is NOT

recommended for SARS(2) Intubation should be performed early once the patie

nt had reached the criteria, and safely, after adequate induction.

Ventilatory care after intubation

1. As usually care for patients with ARDS (adjust FiO2 and PEEP to maintain oxygenation; VT 6-8 cm/kg; plateau pressure < 30-35 cmH2O)

2. Adjunctive procedures that may be helpful for arterial oxygenation (suggested by initial experience): prone positioning (usually effective); albumin infusion and negative I/O balance

Immunomodulating agents for infectious diseases

Cytomegalovirus interstitial pneumonitis in bone marrow recipients: ganciclovir + IVIG

HCV: ribavirin + IFN-2b Respiratory syncytial virus: aerosol ribavirin +/- IVIG (pn

eumonia in immunocompromised patients) (Whimbey et al. BMT 1995;16:393)

EBV: no (IVIG for hemophagocysis) Dengue (endothelial cell injury): no Pneumocystis carinii pneumonia with moderate to seve

re hypoxia: Septrin + steroid (within 72 hr)

Steroid ARDS late stage (>= 7days) (current practice, under st

udy): 1-3mg/kg/day (Marin et al. NEJM 1995; 332:27-37)

Acute interstitial pneumonitis (evidence-base): >1 mg/kg/day

Viral pneumonitis with ARDS (controversial)

The use of steroid after initiation of ribavirin therapy is still controversial and should be judged case-by case Do not use within 48 h of initiation of ribavirin, usuall

y should be after day 7 of disease onset Considered when significant disease progression afte

r ribavirin, (persistent fever with multiple lobe pneumonia, plus multiple laboratory abnormalities, such as hyponatremia, elevated CPK, GOT/GPT, LDH), surge or resurge of CRP, or SpO2 < 95% under nasal O2 5 L/min.

Recommended dose: methylprednisolone 2 mg/kg/day or higher (no evidence support pulse therapy with methylprednisolone 0.5 g ~1g/day is better than lower dose steroid)

The use of IVIG after initiation of ribavirin therapy is also controversial

Clinical observation suggests the potential benefits in cases with evidence suggesting hemophagocytosis (leukopenia in progression, thrombocytopenia, anemia with elevated ferritin), especially when given in accompany with steroids.

Recommended dose: 1gm/kg/day for 2 days.

Adverse reactions to IVIG < 5%

Anaphylaxis

Headache, chills, nausea, fatigue, myalgia, arthralgia, back pain,

Increased blood pressure in patients at risk for hypertension

acute aseptic meningitis wit pleocytosis occur within 48~72 hr

Michel et al. NEJM 2001; 345:747-755

Adverse reactions to IVIG < 5%

Transient increase in creatinine levels within 2~5 days

Acute renal failure is related to tubular damage induced by sucrose in the IVIG preparation, particularly in elderly patients, patients with diabetes or impaired renal function

Transmission of blood-borne agents ?

Pathophysiology of SARS

Incubation Onset of symptoms Progression of disease

CoronavirusHyperinflammationAltered immune response Lymphoid depletion Hemophagocytosis

Viremic phase ARDS

Antiviral + Immunomodulating agent(s)

The Correlation Between Clinical Courses and Serum C-Reactive Protein

Level

All 6 patients developed most severe respiratory distress when they had highest serum CRP level.

The peak levels of 6 patients were all 8 mg/dL, and those of 4 patients who needed mechanical ventilation were all 12 mg/dL.

All 6 patients had deferverence when serum CRP level fell.

A secondary bump in the CRP level occurred during the hospital course with secondary infections.

Goals

Prevent transmission: reduce viral shedding

Reduce mortality

Prevent intubation: improve oxygenation, stop clinical progression to ARDS

Shorten hospitalization: rapid recovery

Reduce long-term sequelae