COVID-19 Scientific Advisory Group Rapid Evidence Report · 2020. 8. 21. · COVID-19 Scientific Advisory Group Topic: What risk factors (such as age, medical conditions, or lifestyle

COVID-19 Scientific Advisory Group Rapid Evidence Report

August 21, 2020 © 2020, Alberta Health Services,

COVID-19 Scientific Advisory Group

Topic: What risk factors (such as age, medical conditions, or lifestyle factors) are associated with the development of severe outcomes in COVID-19?

Key Messages from the Evidence Summary

• The bulk of evidence identified was from jurisdictions with significant health system differences, and differences in the severity of COVID-19 spread, in comparison to Alberta. No evidence on risk factors for severe COVID-19 outcomes was identified from jurisdictions with similar structure or outbreak dynamics to Alberta such as continental Europe, the United Kingdom, Australia, or New Zealand. Evidence from the eastern United States arises from early phases of their outbreak and outcomes may be reflective of a systematically different health system.

• The risk of COVID-19 transmission is not influenced by comorbidities but is a direct reflection of community transmission rates and people's exposure history. The data presented herein evaluate the associations of various health conditions with severe outcomes among patients who have tested positive for COVID-19.

• There is consistent evidence to suggest that increasing age has a consistent and high strength association with hospitalization and death from COVID-19, but a low-moderate strength association with ICU admission. The association is strongest in people older than 65 years and is enhanced in the presence of additional comorbidities.

Context • As Alberta reopens, the risk of SARS-CoV-2 transmission will increase as individuals participate

in sports, in-person classroom activities, musical and theatre performances, and other activities where groups of people congregate.

• Questions have arisen regarding the individual risk of developing severe outcomes for people who acquire COVID-19.

• It is understood that age is a major predictor of COVID-19 severity, however, it is unclear what other underlying or comorbid conditions and lifestyle factors are associated with severe outcomes like hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death.

• A rapid evidence brief was conducted in June 2020 to inform a public-facing risk assessment tool that was developed and published by Alberta Health and the Office of the Chief Medical Officer of Health. The interest generated by the initial brief provided support for a full evidence review and committee discussion on this topic.

• The original rapid evidence brief focused on age, comorbid conditions, pregnancy, and immunosuppressed states. In this current rapid review, we focus on age, comorbid conditions, and pregnancy. Because of the variety of immunosuppressed states (eg. transplant, chemotherapy, immunosuppressive medications), the association between various immunosuppressed states and the development of severe outcomes in COVID-19 will be reported in a forthcoming report.

• This review seeks to inform a variety of decisions, including who should be prioritized for vaccination, but also what types of people might need to be most vigilant in maintaining physical distancing, or who should avoid working in high risk environments

Risk Factors for Severe Disease • 2

• On balance, there is a consistent, low-moderate strength association between male biological sex and severe outcomes of COVID-19. There does not appear to be a difference between hospitalization, ICU admission, or mortality.

• Evidence for the effect of race/ethnicity on COVID-19 outcomes is inconsistent and low strength at best. Six studies showed increased odds of hospitalization for Black or Asian people compared to Caucasian people in the United States. It is unclear if this association is mediated by biological factors or by social determinants of health (such as income, education, access to primary care or systemic racism).

• Other than smoking, individual social and lifestyle factors do not have a consistent association with severe COVID-19. One study found that a composite lifestyle score comprised of smoking history, physical activity, alcohol intake, and obesity was associated with risk of hospitalization, but that individual lifestyle factors alone did not increase risk by a substantial amount.

• Obesity is consistently associated with severe COVID-19. On balance, obesity alone has a high strength association with ICU admission/intubation, especially in those with body mass index (BMI) ≥ 35. Obesity alone has a low strength association with hospitalization and mortality. Obesity was poorly defined in the literature, but the associations were strongest in people with a BMI ≥ 30.

• Diabetes has a consistent moderate strength association with hospitalization from COVID-19, and a low strength association with ICU admission or mortality. Of note, the literature did not distinguish between type 1 and type 2 diabetes.

• Hypertension alone does not have a consistent association with severe COVID-19 outcomes; at best, the association is low strength. The association with severe COVID-19 outcomes increases when hypertension, diabetes, and obesity are co-occurring; however, it is unclear if this relationship is additive or synergistic.

• Cardiovascular disease is poorly defined in the literature and has an inconsistent association with severe COVID-19 outcomes, although chronic heart failure may have an association with worse outcomes. Most studies used “cardiovascular disease” or coronary artery disease for modelling. Notably, large studies looking specifically at chronic heart failure, and meta-analyses of cardiovascular disease showed a stronger association with severe COVID-19 outcomes than small hospital-based studies. More research is needed to clearly determine the risk posed by different chronic cardiovascular conditions.

• Pulmonary disease is poorly defined in the literature, although most included studies used chronic obstructive pulmonary disease (COPD) or asthma in their models. COPD appears to have a low strength association with severe COVID-19 outcomes (on balance, less than 2X increased odds of severity) while asthma appears to have no significant risk of severe COVID-19 (on balance). Notably, large studies and meta-analyses showed a stronger association with severe COVID-19 outcomes than small hospital-based studies. More research is needed to clearly determine the risk posed by different pulmonary conditions.

• Kidney disease was poorly defined in the literature. The association between chronic kidney disease (CKD) and severe outcomes of COVID-19 is consistent but varies by outcome. On balance, the odds or risk of death from COVID-19 associated with CKD appears to be low strength. The risk of hospitalization is higher - studies report a moderate strength association between CKD and hospitalization or ICU admission.

• The association between cancer and COVID-19 outcomes was specifically investigated in three studies. Most included studies considered cancer as a covariate (defined as “cancer” or “malignancy”). Cancer appears to have a low strength association with severe COVID-19 on its own, but is a synergistic factor with age, sex, and other comorbidities.

• Inflammatory Bowel Disease (IBD) was specifically identified and studied in two included articles, with opposing findings. More research is needed to determine the association between IBD and severe COVID-19 outcomes.


• Evidence regarding pregnancy and COVID-19 outcomes is limited. Compared to nonpregnant women, pregnant women may be at higher risk of ICU admission. There is conflicting data on the risk of mortality among pregnant women, with the absolute risk of mortality among pregnant women less than 1% in all published studies (which is similar to appropriate age and comorbidity adjusted control groups). These findings should be interpreted with caution as there are few studies with small sample sizes, limiting the reliability of the estimates of absolute and relative risk. Vertical transmission was been identified in 1.4% of cases in one report. No studies in this review examined the relative risk of fetal developmental concerns or the risk of pregnancy loss, although there appeared to be an association between being infected with COVID-19 and having delivery induction and caesarean delivery

• There is little to no data for patients with rare conditions that are thought to confer higher risk of severe COVID-19 outcomes (eg lung transplant patients, cystic fibrosis), presumably because these patients may have been extremely diligent in public health precautions and are not represented within these study samples. It is unlikely that robust data will be available to quantify the risks to patients with these rare conditions. Patient-specific judgment, with extrapolation from other conditions, will likely be required to mitigate risk to these individuals

Table 1. Strength of association, on balance, between risk factors and occurrence of severe COVID-19 complications (hospitalization, ICU, need for ventilation, death). For each risk factor, there is inconsistency in the associations arising from study size, methodology, and population heterogeneity. Risk factors may be additive, and the presence of more than one increases the risk of severe COVID-19. Because the strength of association is based on relative estimates of risk (eg. OR, HR, RR) compared to individuals without the condition in question, this table does not reflect the absolute risks associated with a particular condition, which may be minimal but still have a consistent, high strength association. The consistency of association reflects consistency across examined studies.

Risk Factor Outcome Strength of Association* Consistency of Association** Number of Studies Included

Age >65 Mortality High High 28 ICU Admission Low-moderate Low 8 Hospital Admission Moderate-high High 10

BMI >35 Mortality Low Low 19 ICU Admission High Moderate 12 Hospital Admission Moderate Moderate 10

Diabetes mellitus Mortality Low-moderate Low 23 ICU Admission Low-moderate Low 14 Hospital Admission Moderate-high High 10

Pregnancy Mortality High* (in one study, see text) Low 3

ICU Admission Moderate-high High 2 Hospital Admission unable to determine, see text)

Male Biological Sex Mortality Low-moderate Moderate 17 ICU Admission Low-moderate Moderate 10 Hospital Admission Low-moderate Moderate 9

Black or Asian race/ethnicity

Mortality Low Low 4 ICU Admission Low Low 6 Hospital Admission Moderate Low 3

Smoking Mortality Low Moderate 3 ICU Admission Low High 4 Hospital Admission Low Moderate 3

Hypertension Mortality Low-moderate Low 21 ICU Admission Low-moderate Low 13 Hospital Admission Low-moderate Low 11


Risk Factor Outcome Strength of Association* Consistency of Association** Number of Studies Included

Cardiovascular Disease

Mortality Low-moderate Low 11 ICU Admission Low Low 8 Hospital Admission Low-moderate Low 5

COPD Mortality Low-moderate Low 11 ICU Admission Low Low 4 Hospital Admission Low-moderate Low 5

Asthma Mortality Low High 6 ICU Admission n/a n/a 2 Hospital Admission Low High 2

Kidney disease Mortality Low Low 14 ICU Admission Low-moderate Low 6 Hospital Admission Low-moderate Low 5

*Cutoffs for the measures of association are derived from Chen, Cohen & Chen (2010) and are reconciled with the potential clinical importance by the following terms and cutoff points: low strength associations (not significant (n.s.), OR 2.5). **Consistency of association is determined as follows: High consistency (all relevant studies show an association of similar strength); moderate consistency (≥ 80% relevant studies show an association, but the strength of the association is variable); low consistency (more than 50% of findings show no effect)

Committee Discussion Overall, the committee was in agreement that the body of evidence on which this review is based is of reasonably high methodological quality. However, the committee noted some areas in which the findings of this data are limited. The committee noted that the bulk of evidence identified was from jurisdictions with significant health system differences, and differences in the severity of COVID-19 spread, in comparison to Alberta. For instance, evidence from the eastern United States arises from early phases of their outbreak and outcomes may be reflective of a systematically different health system and geography, and where patients had higher levels of exposure than observed in Alberta. In the US, a large proportion of severe outcomes were experienced by un/under-insured patients with limited access to care, so their risk may be higher than patients with similar conditions in Alberta.

The committee also discussed challenges in disentangling the risks posed by specific medical conditions from factors that may be associated with a particular disease such as race/ethnicity and socioeconomic status. Committee members expressed a desire for more data that might disentangle the relationship between COVID outcomes, specific comorbid medical conditions and race/ethnicity and socioeconomic status. However, the committee felt on balance that the evidence identifying strong associations with higher risk of adverse outcomes with advancing age is robust, and that the elevated risk of ICU admission associated with pregnancy appears concerning.. The committee expressed a desire for more data on both the absolute risks and relative risks of severe COVID-19 disease and severe outcomes in pregnant patients, particularly mortality, including the relationship across pregnancy stage. There was also agreement that drawing strong conclusions on the relationship between COVID-19 outcomes in cardiovascular disease, chronic lung disease, cancer and other rare conditions (eg lung transplant, cystic fibrosis) is challenging given the heterogeneity in how these conditions are defined in the literature, and because of the small sample size of many of the primary studies. Finally, it is acknowledged that immunosuppression is not clearly defined and assessed in these studies and is the subject of a dedicated review that is in progress.

Principal Findings 1. Age is strongly and consistently associated with severe COVID-19 outcomes, including death. The risk is

highest for those 65 years or older, although increased risk is observed for individuals over the age of 50.


2. Pregnancy may be associated with higher risk of ICU admission for COVID-19, compared to nonpregnant patients. One study suggested an elevated mortality risk in pregnancy and severe outcomes appear to be more common in pregnant women with COVID-19 who have comorbidities such as diabetes, and heart and lung conditions. However, the absolute risk of mortality for pregnant patients with COVID-19 is low (


addition, the impact on fetal outcomes is important to understand. A future SAG review focusing on the risk on pregnant women will be undertaken as additional information is available

• A forthcoming study on the clinical epidemiology of COVID-19 in Alberta will be useful for informing public health activities based on the health and pre-existing risk factors that are prevalent in Alberta.

Strength of Evidence The body of evidence included is generally strong. Most of the included studies were peer-reviewed (9 preprint articles were included) and the findings from the included studies were remarkably consistent across jurisdiction, study size, methodology, and specific conditions of interest to the authors. The risk of selection bias for forming cohorts was relatively low, as the prospective studies often used consecutively admitted COVID-19 patients and the retrospective studies often used the entire population of people who tested positive for COVID-19. The systematic reviews were of high quality and included a significant amount of the Chinese epidemiological literature, which was excluded from the primary source review herein due to lack of a similarity with the Alberta population and due to translation challenges.

Limitations of this review The limitations of this review stem from the breadth of the topic and from the unequal distribution of literature arising from specific regional COVID-19 outbreaks. The relative over-representation of cases from New York, Italy, and Mexico may artificially increase the importance of a given risk factor as there may be overlapping datasets (so patients may have been included more than once). Likewise, the included systematic reviews and meta-analyses largely used Chinese studies, so there may be overlapping data across these articles as well.

Databases were searched for English-language evidence published in 2020, thus, evidence from outbreaks in jurisdictions where English is not common has not been included in this review.

Summary of Evidence Sixty-six articles were included in the narrative evidence synthesis below. Of these, there were 12 systematic reviews, 11 prospective cohort studies, 37 retrospective studies, and 6 case series. Two were studies identified ad hoc that related to the relationship between pregnancy and severe COVID-19. Due to the availability of primary literature, no grey literature was included in this review.

The jurisdiction distribution of the studies was as follows: International dataset (1) United States (23 from 3 national datasets and 9 states); Mexico (7); Italy (6); Spain (4); United Kingdom (4); France (3); Sweden (1); Denmark (1); Switzerland (1); and Turkey (1). From the United States, COVID-19 outbreaks from New York (10), Los Angeles (1), Pennsylvania (2), Massachusetts (2), Chicago (1), Rhode Island (1), Georgia (2), Louisiana (1), Detroit (1), and national data (3) were captured. The findings from the individual studies are included in the evidence extraction table (Table 24) in the appendix.

What risk factors (such as age, medical conditions, or lifestyle factors) are associated with the development of severe outcomes in COVID-19? Measures of association between pre-existing medical conditions, biological, or lifestyle determinants of health and severe outcomes of COVID-19 were reported in all 64 included studies. In this review, “severe outcomes” is defined as hospitalization, critical care admission (and mechanical ventilation) and death. Of note, any risk related to immunosuppression was determined to be out of scope of this review, as there is an upcoming rapid review focused on that topic and its nuances. Likewise, risk conferred by characteristics that could only be determined by lab testing was not considered in this review. Risk factors that were commonly considered by study authors are included here: age, sex, race/ethnicity, smoking, obesity, diabetes, hypertension, cardiovascular disease, pulmonary disease, kidney disease, cancer, inflammatory bowel disease, and pregnancy.

Risk Factors for Severe Disease • 7 Many of the conditions identified as risk factors are closely related and co-occurring and may have a synergistic effect on the course of COVID-19 disease. Denova-Gutierrez et al. (2020), Kammar-Garcia et al. (2020), and Wang, Zhong & Hurd (2020) each specifically show that the presence of multiple comorbidities increases the risk of death compared to one comorbidity or no comorbidities. Further, the interaction of non-disease risk factors can influence risk of outcomes, such as between social determinants of health and age (Bello-Chavolla et al., 2020b) between related comorbidities such as diabetes, hypertension, and obesity (Bello-Chavolla et al., 2020a) or between multiple lifestyle factors (Hamer et al., 2020). These associations increase the risk of severe outcomes compared to the risk of one factor alone.

Where available, the associations listed in the tables below are obtained through multivariable analysis, indicating that, in the context of the variables measured, they are independently associated with severe outcomes. Because of varying study designs, the individual measures of association were unable to be pooled in this rapid review. Only five of the included 64 studies used univariate analysis – Collin et al. (2020), Martinez-Portilla et al. (2020), Földi et al., (2020), Lee et al. (2020) and Lippi et al. (2020). All other studies used multivariate methodology to determine association. The interpretation of the strength of association is guided by the observations of Chen, Cohen & Chen (2010), who show the relationship between Cohen’s d and odds ratio (OR), hazard ratio (HR), or risk ratio (RR) . By their rules, a moderate to strong association occurs when most studies show OR>3.47 or HR/RR >2.5; a weak association occurs when most studies show OR 1.68-3.47; HR/RR 1.5-2.5; and no association when OR < 1.67 and HR/RR


Reference Jurisdiction Study Size Age Outcome (Comparator) Association Age 51-60 yrs Hospitalization (≤ 20 yrs) OR 5.27 (4.37-6.36) Age 61-70 yrs Hospitalization (≤ 20 yrs) OR 8.97 (7.39-10.88) Age > 70 yrs Hospitalization (≤ 20 yrs) OR 11.6 (9.48-14.19)

Carrillo-Vega et al., 2020

Mexico 10544 Age 50-74 years

Hospitalization (25-49 yrs)

OR 2.05 (1.81-2.32)

Age ≥ 75 years Hospitalization (25-49 yrs)

OR 3.84 (2.90-5.10)

Ebinger et al., 2020

United States (CA)

442 Older age Severity (per 10 years) OR 1.49 (1.30-1.70)

Golpe et al., 2020 Spain 539 Older age Hospitalization OR 1.04 (1.00-1.08) Killerby et al., 2020

United States (GA)

531 Age 45-64 years

Hospitalization (Age 18-44)

n.s.

Age ≥ 65 years Hospitalization (Age 18-44)

aOR 3.4 (1.6-7.4)

Ko et al., 2020 United States (national)

5416 Age 45-64 years

Hospitalization (18-44 yrs)

aRR 2.0 (1.6-2.3)

Age 65+ years Hospitalization (18-44 yrs)

aRR 2.9 (2.4-3.5)

Martinez-Lopez et al., 2020

Spain 167 Age >65 yrs Hospitalization (Age


Reference Jurisdiction Study Size Age Outcome (Comparator) Association Age 70-79.9

ICU admission (Age


Reference Jurisdiction Study Size Age Outcome (Comparator)

Association

Lieberman-Cribbin et al., 2020

Age >69 + asthma

Mortality (Age 65) OR 0.23 (0.07-0.61)

Nakeshbandi et al., 2020

United States (NY)

504 Age 45-64 Mortality (Age


Reference Jurisdiction Study Size Outcome (Female comparator)

Association

Berumen et al., 2020 Mexico 102875 Hospitalization OR 1.67 (1.6-1.75) Carrillo-Vega et al., 2020 Mexico 10544 Hospitalization OR 1.54 (1.37-1.74) Ebinger et al., 2020 United States (CA) 442 Severity OR 2.01 (1.24-3.04) Golpe et al., 2020 Spain 539 Hospitalization n.s. Killerby et al., 2020 United States (GA) 531 Hospitalization aOR 2.4 (1.4-4.1) Ko et al., 2020 United States

(National) 5416 Hospitalization aRR 1.2 (1.1-1.4)


Spain 167 Hospitalization aOR 2.3 (1.1-4.4)

Petrilli et al., 2020 United States (NY) 5279 Hospitalization OR 2.76 (2.39-3.2) Price-Haywood et al., 2020

United States (LA) 3626 Hospitalization (male comparator)

OR 0.56 (0.48-0.65)

Wang et al., 2020 United States (Mass)

1827 Hospitalization OR 1.75 (1.36-2.24)

Table 6. Association between male sex and ICU admission/intubation from COVID-19. Low strength associations (not significant (n.s.), OR 2.5) are shaded red. Studies where “male” was the referent have not been highlighted.


Association

Argenziano et al., 2020 United States (NY) 1000 Intubation (Male comparator) HR 0.71 (0.54-0.95) Fang et al., 2020 Meta-analysis 61 studies >

10000 each Severity RR 1.20 (1.13-1.27)

Hur et al., 2020 United States (IL) 486 Intubation OR 1.69 (1.04-2.77) Jain et al., 2020 Meta-analysis 1813 ICU admission pOR 1.55 (1.02-2.36) Kim et al., 2020 United States

(National) 2491 ICU admission aRR 1.34 (1.2-1.5)

Kragholm et al., 2020 Denmark 4842 ICU admission RR 2.22 (1.70-2.91) Nakeshbandi et al., 2020 United States (NY) 504 Intubation n.s. Regina et al., 2020 Switzerland 200 Intubation aOR 3.26 (1.21-9.80) Rottoli et al., 2020 Italy (Bologna) 482 ICU admission n.s. Simonnet et al., 2020 France (Lille) 124 Invasive Mechanical

Ventilation OR 2.83 (1.02-7.85)

Suleyman et al., 2020 United States (MI) 463 ICU admission OR 2.0 (1.3-3.2) pOR: pooled Odds Ratio

Table 7. Association between male sex and COVID-19 mortality. Low strength associations (not significant (n.s.), OR 2.5) are shaded red. Studies where “male” was the referent have not been highlighted.


Association

Albitar et al., 2020 International 828 Death aOR 1.08 (1.06-10.9) Argenziano et al., 2020 United States (NY) 1000 Death (Male comparator) n.s. Atkins et al., 2020 United Kingdom 269070 Death OR 2.12 (1.45-3.09) Cariou et al., 2020 France 1317 Death (Male comparator) n.s. Carrillo-Vega et al., 2020 Mexico 10544 Death OR 1.53 (1.30-1.81) Ciceri et al., 2020 Italy (Milan) 410 Death n.s. Cummings et al., 2020 United States (NY) 257 Death n.s. Docherty et al., 2020 United Kingdom 20133 Death (Male comparator) HR 0.81 (0.75-0.86)


Grasselli et al., 2020 Italy (Lombardy) 3988 Death HR 1.57 (1.31-1.88) Kim et al., 2020 United States

(National) 2491 Death aRR 1.30 (1.14-1.49)

Kragholm et al., 2020 Denmark 4842 Death RR 1.53 (1.30-1.80) Lee et al., 2020 United Kingdom 800 Death OR 1.67 (1.19-2.34) Leiberman-Cribbin et al., 2020

United States (NY) 6245 Death (Male comparator) OR 0.70 (0.59-0.82)

Nakeshbandi et al., 2020 United States (NY) 504 Death RR 1.3 (1.0-1.5) Palaiodimos et al., 2020 United States (NY) 200 Death OR 2.74 (1.25-5.98) Price-Haywood et al., 2020

United States (LA) 3626 Death (Male comparator) OR 0.56 (0.49-0.78)

Rivera-Izquierdo et al., 2020

Spain (Granada) 238 Death n.s.

Rotolli et al., 2020 Italy (Bologna) 482 Death HR 1.98 (1.26-3.10) Salacup et al., 2020 United States (PA) 242 Death (Male comparator) n.s. Shah et al., 2020 United States (GA) 522 Death (Male comparator) OR 0.41 (0.24-0.70) Van Gerwen et al., 2020 United States (NY) 3703 IMV & Death OR 2.04 (1.28-3.26) Zheng et al., 2020 Meta-analysis 3027 Critical/Death OR 1.77 (1.43-2.19)

Race/Ethnicity Race/Ethnicity of COVID-19 patients was considered in 13 of the 64 included studies, mostly in evidence from the United States (Table 8). The association between race/ethnicity and severe COVID-19 outcomes is low strength at best and is not consistent across studies. Four studies report a significant association between Black race and severe COVID-19 outcomes or mortality (Atkins et al., 2020; Ebinger et al., 2020; Ko et al., 2020; Price-Haywood et al., 2020). A low strength association between Asian race and hospitalization was reported in three studies (Haijfathalian et al., 2020; Ko et al., 2020; Wang et al., 2020). The other eight studies found no significant association or minimal association between race/ethnicity and COVID-19 severity. It is unclear if this association is mediated by biological factors or by social determinants of health, as these groups are often disadvantaged in the United States and may experience socioeconomic and health disparities that lead to weaker health overall.

No published Canadian data was identified in the literature search, and specifically no data on COVID-19 severity or outcomes among Indigenous Canadians was identified or included in this review.

Table 8. Association between race/ethnicity and severe outcomes of COVID-19. Low strength associations (not significant (n.s.), OR 2.5) are shaded red.

Reference Jurisdiction Study Size Race/Ethnicity Outcome (comparator) Association Atkins et al., 2020 United Kingdom 269070 Black Death (White) OR 2.6 (1.09-6.19)

South Asian Death (White) n.s. Ciceri et al., 2020 Italy (Milan) 410 Non-European Death (European) n.s. Ebinger et al., 2020

United States (CA)

442 African American Severity (non-African American)

OR 2.13 (1.19-3.83)

Hispanic Severity (non-Hispanic) n.s. Haijafathalian et al., 2020

United States (NY)

770 Black / African-American

ICU admission or death (White/Caucasian)

n.s.

Asian ICU admission or death (White/Caucasian)

RR 1.53 (1.08-2.17)

Hur et al., 2020 United States (IL)

486 African American Intubation (non-Hispanic White)

n.s.

Hispanic White Intubation (non-Hispanic White)

n.s.

Asian/other Intubation (non-Hispanic White )

n.s.


Reference Jurisdiction Study Size Race/Ethnicity Outcome (comparator) Association Kalligeros et al., 2020

United States (RI)

103 Non-Hispanic Black

ICU admission (non-Hispanic White)

n.s.

Hispanic ICU admission (non-Hispanic White)

n.s.

Ko et al., 2020 United States (National)


Hospitalization (non-Hispanic White)

aRR 4.0 (3.4-4.8)

Other race/ethnicity

Hospitalization (non-Hispanic White)

aRR 3.3 (2.8-4.0)

Petrilli et al., 2020 United States (NY)

5279 Hispanic Hospitalization (Non-Hispanic/White)

OR 1.63 (1.35-1.97)

Price-Haywood et al., 2020

United States (GA)

3626 Race (Black) Hospitalization (White) OR 1.96 (1.62-2.37)

Mortality (White) n.s. Salacup et al., 2020

United States (PA)

242 Caucasian Mortality (African American)

n.s.

Hispanic Mortality (African American)

n.s.

Shah et al., 2020 United States (GA)

522 Black Mortality (White) n.s.

Suleyman et al., 2020

United States (IL)

463 African American ICU admission (White) n.s.

Van Gerwen et al., 2020

United States (NY)


IMV & Death (NH White)

n.s.

Other race IMV & Death (NH White)

n.s.


1827 Black Hospitalization (White) aOR 1.65 (1.19-2.27)

Asian Hospitalization (White) aOR 3.19 (1.56-6.54)

Hispanic Hospitalization (White) n.s.

Social and Lifestyle Factors Bello-Chavolla et al. (2020b) tested the role of social determinants of health on risk of severe outcomes. Older adults who were socially disadvantaged (measured by the composite Social Lag Index (SLI) measure) had a low strength but significant increase in their odds of hospitalization (1.5X increase), intubation (1.4X increase) and death (1.1X) from COVID-19, compared to older adults who did not face structural barriers to health equity (Bello-Chavolla et al., 2020b).

Lifestyle factors do not appear to be significantly associated with severe outcomes of COVID-19. Hamer et al. (2020) conducted a population-based cohort study based on community data from 387109 UK residents. In their study, risk of hospitalization from COVID-19 had a moderate-high strength association with a composite lifestyle score comprised of smoking history, physical activity, alcohol intake, and obesity. Relative risk of hospitalization increased by 2.4X at a slightly sub-optimal lifestyle, up to a 3.7X increase in risk of hospitalization for those with the “worst” lifestyle (Hamer et al., 2020). Hamer (2020) also showed a low strength risk of hospitalization for those who do no physical activity (RR 1.38 (1.15-1.64)); those who consume more alcohol than recommended guidelines (RR 1.24 (1.03-1.50)), and those who are overweight but not obese (RR 1.32 (1.09-1.60)). A moderate strength association was found between risk of hospitalization and those who rarely consume alcohol (RR 1.57 (1.31-1.88)) and those who are obese (RR 1.97 (1.61-2.42)) (Hamer et al., 2020).

Studies that tested the contribution of smoking status to COVID-19 severity show that there is an inconsistent association that is low strength at best (Table 9). More research is needed to determine the mechanism of this (lack of) association.

Risk Factors for Severe Disease • 14 Table 9. Association between smoking and severe COVID-19 outcomes. Low strength associations (not significant (n.s.), OR 2.5) are shaded red.

Reference Jurisdiction Study Size Smoking Status

Outcome (comparator) Association

Algahtani et al., 2020

Meta-analysis 2473 Current Severe complications (former or never smoker)

RR 1.45 (1.03-2.04)

Argenziano et al., 2020

United States (NY)

1000 Current or Former

Intubation or death (never smoker)

n.s.

Fang et al., 2020 Meta-analysis 61 studies > 10000 each

Current or Former

Severity (never smoker) n.s.

Hamer et al., 2020

United Kingdom 387109 Past smoker Hospitalization (never smoked)

RR 1.36 (1.15-1.59)

Current smoker

Hospitalization (never smoked)

RR 1.36 (1.08-1.71)

Killerby et al., 2020

United States (GA)

531 Past or current smoking

Hospitalization (never smoked)

aOR 2.3 (1.2-4.5)

Palaiodimos et al., 2020

United States (NY)

200 Current or former smoker

Mortality (never smoker) n.s.


United States (NY)

3703 Current or past smoker

IMV & Death (never smoked)

n.s.

Wang, Zhong & Hurd, 2020

United States (NY)

7592 Former smoker Death (never smoked) OR 1.27 (1.01-1.60) Current smoker

Death (never smoked) n.s.


1827 Current or former smoker

Hospitalization (never smoker)

n.s.

Obesity Obesity is consistently associated with severe outcomes of COVID-19. Risk of hospitalization has a low strength association with obesity (Table 10); however, risk of ICU admission/intubation is consistently associated with increasing body mass index (BMI), with a high strength association between BMI >35 and ICU admission or intubation (Table 11). Risk of mortality had low strength association with obesity (Table 12). There is low strength association with mortality at BMI >35, and no association for normal weight or overweight people. Of note, the risk of severe COVID-19 outcomes has been shown to increase when diabetes, hypertension, and obesity are co-occurring, and the risk of hospitalization and death is higher than for any of the three conditions alone (Carrillo-Vega et al., 2020). The synergistic or additive nature of this relationship is unclear.

Table 10. Association between obesity and COVID-19 hospitalization. Low strength associations (not significant (n.s.), OR 2.5) are shaded red. Studies where BMI was undefined are denoted in the table as “—“.

Reference Jurisdiction Study Size BMI range Outcome (comparator)

Association

Bello-Chavolla et al., 2020b

Mexico 20804 -- Hospitalization (no comorbidity)

OR 1.45 (1.45-1.71)

Berumen et al., 2020

Mexico 102875 -- Hospitalization (non-obese)

OR 1.47 (1.39-1.55)


Mexico 10544 -- Hospitalization (no comorbidity)

OR 1.64 (1.37-1.95)


United States (CA)

442 -- Severity (non-obese) OR 1.95 (1.11-3.42)

Hamer et al., 2020

United Kingdom

387109 Overweight Hospitalization (Healthy weight)

RR 1.32 (1.09-1.60)



Association

Obesity Hospitalization (Healthy weight)

RR 1.97 (1.61-2.42)


United States (GA)

531 Obesity Hospitalization (non-obese)

aOR 1.9 (1.1-.3)


5416 Obesity (undefined)

Hospitalization (non-obese)

aRR 2.9 (2.3-3.5)


5279 BMI 30.0-39.9 Hospitalization (BMI < 25)

OR 1.8 (1.47-2.2)

BMI ≥ 40 Hospitalization (BMI < 25)

OR 2.45 (1.78-3.36)

Price-Haywood et al., 2020

United States (GA)

3626 Obesity (undefined)

Hospitalization (non-obese)

OR 1.43 (1.20-1.71)

Table 11. Association between obesity and COVID-19 ICU admission/intubation. Low strength associations (not significant (n.s.), OR 2.5) are shaded red. Studies where BMI was undefined are denoted in the table as “—“.


Association


United States (NY)

1000 -- Intubation (lower BMI) n.s.

Bello-Chavolla et al., 2020b

Mexico 20804 Obesity (undefined)

Intubation (no comorbidity)

OR 1.5 (1.13-2.05)

Denova-Gutierrez et al., 2020

Mexico 22287 Obesity (undefined)

Severe COVID-19 (non-obese)

OR 1.43 (1.11-1.83)

Obesity * Male Severe COVID-19 (non-obese male)

OR 1.75-1.15-2.57)

Obesity * Female

Severe COVID-19 (non-obese female)

OR 1.30-1.03-1.81)

Földi et al., 2020 Meta-analysis 2770 Obesity (BMI ≥ 25)

ICU admission (BMI < 25)

pOR 1.21 (1.00-1.46)

Invasive Mechanical ventilation (BMI < 25)

pOR 2.05 (1.16-3.64)

BMI 25-30 IMV (BMI < 25) pOR 2.18 (1.24-3.56) BMI 30-35 IMV (BMI < 25) pOR 2.34 (1.33-4.10) BMI ≥ 35 IMV (BMI < 25) pOR 5.89 (2.92-11.84) BMI 30-35 IMV (BMI 25-30) pOR 1.85 (1.08-3.17) BMI ≥ 35 IMV (BMI 25-30) pOR 2.95 (1.48-5.89) BMI ≥ 35 IMV (BMI 30-35) pOR 2.52 (1.15-5.50)

Harmouch et al., 2020

United States (PA)

563 -- ICU admission OR 1.04 (1.01-1.08) Invasive Mechanical ventilation

OR 1.04 (1.01-1.08)

Hur et al., 2020 United States (IL)

486 BMI 30-39.99 Intubation (BMI



Association

Invasive Mechanical ventilation (BMI 30)

Intubation (BMI 18.5-24.99)

RR 2.4 (1.5-4.0)

Rottoli et al., 2020 Italy (Bologna) 482 Obesity (BMI ≥ 30)

ICU admission (BMI



Association

Kammar-Garcia et al., 2020

Mexico 13842 -- Mortality (no disease) HR 1.8 (1.6-2.1)

Kim et al., 2020 United States (National)

2491 Obesity (BMI ≥ 30)

Mortality (non-obese) n.s.


United States (NY)

504 Overweight (BMI 25-29.9)

Mortality (BMI 18.5-24.99)

RR 1.4 (1.1-1.9)

Obese (BMI>30)

Mortality (BMI 18.5-24.99)

RR 1.3 (1.0-1.7)


United States (NY)

200 BMI


Table 14. Association between diabetes and COVID-19 ICU admission/intubation. Low strength associations (not significant (n.s.), OR 2.5) are shaded red. The comparator for all studies was “no diabetes”.

Reference Jurisdiction Study Size Outcome (comparator) Association Al-Salameh et al., 2020 France 326 ICU admission OR 2.06 (1.09-3.92) Argenziano et al., 2020 United States (NY) 1000 Intubation or death n.s. Denova-Gutierrez et al., 2020

Mexico 22287 Severe COVID-19 (non-diabetic)

OR 1.87 (1.41-4.26)

Severe COVID-19 (non-diabetic male)

OR 1.87 (1.19-2.94)

Severe COVID-19 (non-diabetic female)

OR 1.86 (1.30-2.64)


Severity RR 1.95 (1.60-2.36)

Huang et al., 2020 Meta-analysis 6452 ICU care n.s. Hur et al., 2020 United States (IL) 486 Intubation OR 1.64 (1.02-2.66) Jain et al., 2020 Meta-analysis 1813 ICU admission n.s. Kalligeros et al., 2020 United States (RI) 103 ICU admission n.s. Kim et al., 2020 United States

(national) 2491 ICU admission aRR 1.13 (1.03-1.24)


United States (NY) 504 Intubation (no disease) n.s.

Roncon et al., 2020 Meta-analysis 1382 ICU admission OR 2.79 (1.85-4.22) Rottoli et al., 2020 Italy (Bologna) 482 ICU admission (no

disease) n.s.

Simonnet et al., 2020 France (Lille) 124 Invasive mechanical ventilation

n.s.

Suleyman et al., 2020 United States (MI) 463 ICU admission n.s.

Table 15. Association between diabetes and COVID-19 mortality. Low strength associations (not significant (n.s.), OR 2.5) are shaded red. The comparator for all studies was “no diabetes”.

Reference Jurisdiction Study Size Outcome (comparator) Association Al-Salameh et al., 2020 France 326 Death n.s. Albitar et al., 2020 International 828 Death aOR 12.2 (4.1-36.3) Atkins et al., 2020 (Type II diabetes)

United Kingdom 269070 Death OR 3.11 (2.06-4.71)

Bello-Chavolla et al., 2020a

Mexico 51633 Death (No diabetes) HR 1.34 (1.26-1.43) Death (Late-onset diabetes)

HR 2.86 (2.19-3.76)


Mexico 10544 Death OR 1.50 (1.13-1.98)

Ciceri et al., 2020 Italy (Milan) 410 Death n.s. Cummings et al., 2020 United States (NY) 257 Death n.s. Docherty et al., 2020 United Kingdom 20133 Death n.s. Grasselli et al., 2020 (Type II diabetes)

Italy (Lombardy) 3988 Death HR 1.18 (1.01-1.39)

Hashemi et al., 2020 United States (Mass) 363 Death n.s. Huang et al., 2020 Meta-analysis 6452 Death RR 2.12 (1.44-3.11)


Reference Jurisdiction Study Size Outcome (comparator) Association Kammar-Garcia et al., 2020

Mexico 13842 Death (non-diabetic) HR 1.9 (1.8-2.2) Death (no COPD) HR 2.4 (1.2-4.8) Death (no hypertension) HR 2.7 (2.2-3.3) Death (no obesity) HR 2.9 (2.1-4.1) Death (no CKD) HR 4.02 (1.7-9.8)

Kim et al., 2020 United States (national)

2491 Mortality aRR 1.19 (1.01-1.40)

Lee et al., 2020 (Active Cancer)

United Kingdom 800 Mortality (no diabetes) OR 1.61 (1.03-2.48)

Martinez-Portilla et al., 2020 (Pregnancy)

Mexico 1241 Mortality (no diabetes) OR 40 (6.20-258.0)


United States (NY) 504 Mortality (no diabetes) n.s.

Palaiodimos et al., 2020 United States (NY) 200 Mortality n.s. Rivera-Izquierdo et al., 2020

Spain (Granada) 238 Death HR 2.42 (1.43-4.09)

Roncon et al., 2020 Meta-analysis 1382 Death OR 3.21 (1.82-5.64) Rottoli et al., 2020 Italy (Bologna) 482 Death (no disease) n.s. Salacup et al., 2020 United States (PA) 242 Death n.s. Shah et al., 2020 United States (GA) 522 Death n.s. Zheng et al., 2020 Meta-analysis 3027 Critical/Death OR 3.68 (2.68-5.03)

Hypertension Hypertension is not consistently associated with severe outcomes of COVID-19 (Tables 16, 17,18). Associations are more commonly seen in large studies (n>1000), but on balance, the association is low strength. Hypertension appears to increase risk– alone, the risk appears to be low, the risk of ICU admission and mortality is increased when combined with other factors such as male sex (Denova-Gutierrez et al., 2020), diabetes and obesity, however it is unclear if the relationship with these factors is additive or synergistic (Carrillo-Vega et al., 2020, Kammar-Garcia et al., 2020) and CKD (Kammar-Garcia et al., 2020).

Anti-hypertensive medications such as angiotensin-converting enzyme (ACE) inhibitors (ACEI) and angiotensin receptor blockers (ARB) were not shown to increase the risk of severe COVID-19 outcomes (Golpe et al. 2020; Guo et al., 2020; Giacomelli et al., 2020).

Table 16. Hypertension and COVID-19 hospitalization. Low strength associations (not significant (n.s.), OR 2.5) are shaded red.

Reference Jurisdiction Study Size Outcome (comparator) Association Berumen et al., 2020 Mexico 102875 Hospitalization OR 2.79 (2.64-2.95) Carrillo-Vega et al., 2020

Mexico 10544 Hospitalization OR 1.54 (1.26-1.88)

Ebinger et al., 2020 United States (CA) 442 Severity n.s. Golpe et al., 2020 Spain 539 Hospitalization (no

ACEI) n.s.

Hospitalization (no ARB)

OR 0.29 (0.10-0.88)

Guo et al., 2020 Meta-analysis 3936 Disease severity (no ACEI/ARB)

n.s.

Killerby et al., 2020 United States (GA) 531 Hospitalization n.s. Ko et al., 2020 United States

(National) 5416 Hospitalization aRR 2.8 (2.3-3.4)

Liu et al., 2020 Meta-analysis 10948 Severe COVID-19 pOR 2.84 (2.22-3.63)


Reference Jurisdiction Study Size Outcome (comparator) Association Martinez-Lopez et al., 2020

Spain 334 Hospitalization n.s.

Petrilli et al., 2020 United States (NY) 5279 Hospitalization OR 1.78 (1.49-2.12) Wang et al., 2020 United States (Mass) 1827 Hospitalization n.s.

Table 17. Hypertension and COVID-19 ICU admission/intubation. Low strength associations (not significant (n.s.), OR 2.5) are shaded red.

Reference Jurisdiction Study Size Outcome (comparator) Association Argenziano et al., 2020

United States (NY) 1000 Intubation n.s.

Denova-Gutierrez et al., 2020

Mexico 22287 Severe COVID-19 (non-hypertensive male)

OR 2.33 (1.56-3.49)

Severe COVID-19 (non-hypertensive female)

OR 1.50 (1.07-2.08)


Severity (non-hypertensive)

RR 2.09 (1.74-2.52)

Jain et al., 2020 Meta-analysis 1813 ICU admission pOR 3.65 (2.22-5.99) Kalligeros et al., 2020 United States (RI) 103 ICU admission n.s. Kim et al., 2020 United States

(National) 2491 Severe outcomes n.s.

Lippi et al., 2020 Meta-analysis 2893 Severe COVID-19 (No hypertension)

pOR 2.49 (1.98-3.12)


United States (NY) 504 Intubation (no disease) n.s.

Pranata et al., 2020 Meta-analysis 6560 ICU care RR 2.11 (1.24-3.33) Regina et al., 2020 Switzerland 200 Mechanical ventilation n.s. Rottoli et al., 2020 Italy (Bologna) 482 ICU admission (no

disease) n.s

Simonnet et al., 2020 France (Lille) 125 Invasive mechanical ventilation

n.s.

Suleyman et al., 2020 United States (MI) 463 ICU admission n.s.

Table 18. Hypertension and COVID-19 mortality. Low strength associations (not significant (n.s.), OR 2.5) are shaded red.

Reference Jurisdiction Study Size Outcome (comparator) Association Albitar et al., 2020 International 828 Death aOR 3.6 (1.7-7.5) Argenziano et al., 2020

United States (NY) 1000 Death HR 1.59 (1.1-2.3)

Atkins et al., 2020 United Kingdom 269070 Death n.s. Cariou et al., 2020 France 1317 Death n.s. Carrillo-Vega et al., 2020

Mexico 10544 Death OR 1.49 (1.15-1.92)

Ciceri et al., 2020 Italy (Milan) 410 Death n.s. Cummings et al., 2020 United States (NY) 257 Death n.s. Giacomelli et al., 2020 Italy (Milan) 233 Death (no anti-

hypertensive meds) n.s.

Grasselli et al., 2020 Italy (Lombardy) 3988 Death n.s. Guo et al., 2020 Meta-analysis 3936 Death (no ACEI/ARB) OR 0.57 (0.38-0.84) Kammar-Garcia et al., 2020

Mexico 13842 Death HR 1.6 (1.5-1.8) Death (no diabetes) HR 2.7 (2.2-3.3)


Reference Jurisdiction Study Size Outcome (comparator) Association Death (no CKD) HR 2.9 (1.6-5.1)

Lee et al., 2020 (Active cancer)

United Kingdom 800 Death OR 1.95 (1.36-2.80)

Lippi et al., 2020 Meta-analysis 2893 Death (No hypertension)

pOR 2.42 (1.51,3.90)


United States (NY) 504 Mortality (no disease) n.s.


United States (NY) 200 Mortality n.s.

Pranata et al., 2020 Meta-analysis 6560 Mortality RR 2.21 (1.74-2.81) Rivera-Izquierdo et al., 2020

Spain (Granada) 238 Death n.s.

Rottoli et al., 2020 Italy (Bologna) 482 Death (no disease) n.s. Shah et al., 2020 United States (GA) 522 Mortality OR 3.36 (1.3-8.6) Van Gerwen et al., 2020

United States (NY) 3703 IMV and Death OR 1.64 (1.11-2.68)

Zheng et al., 2020 Meta-analysis 3027 Critical/Death OR 2.72 (1.60-4.64)

Cardiovascular Disease Cardiovascular disease (CVD) “chronic heart disease” (CHD) was poorly defined in the included studies, but on balance appears to be low strength as a risk factor for severe outcomes of COVID-19 (Table 19). Large studies and meta-analyses appear to show a stronger association, so more research is needed to identify the nuances of “cardiovascular disease” and separate the specific ailments such as coronary artery disease (CAD), congestive heart failure (CHF), atrial fibrillation (AF), or myocardial infarction (MI) that contribute to COVID-19 risk. One large prospective cohort specifically identifies chronic heart failure as having a strong association with adverse outcomes, but there does not appear to be a strong association between either coronary artery disease or atrial fibrillation and adverse outcomes. There is a clear discrepancy between the low strength associations found by single primary studies and the moderate-high strength associations found by large meta-analytic studies. These differences signal higher risk in chronic heart failure, but more research is needed to understand the mechanism and strength of association.

Table 19. Associations between cardiovascular disease and severe COVID-19 outcomes. Low strength associations (not significant (n.s.), OR 2.5) are shaded red.

Reference Jurisdiction Study Size Condition Outcome/ (comparator)

Association

Albitar et al., 2020 International 828 CVD Death (no disease) n.s. Argenziano et al. 2020

United States (NY)

1000 CAD Intubation or death n.s. CHF Intubation or death n.s.

Atkins et al., 2020 United Kingdom

269070 CHD Death (no disease) n.s. Atrial fibrillation Death (no disease) n.s.

Cariou et al., 2020

France 1317 Heart failure Death (no disease) n.s.

Ciceri et al., 2020 Italy (Milan) 410 CAD Death (no disease) HR 2.93 (1.77-4.86) Cummings et al., 2020

United States (NY)

257 CAD or CHF Death (no disease) HR 1.76 (1.08 – 2.86)

Docherty et al., 2020

United Kingdom

20133 Chronic cardiac disease

Death (no disease) HR 1.16 (1.08-1.24)


United States (CA)

442 Prior Heart failure or MI

Severity (no heart failure)

n.s.



Association


Cardiovascular disease

Severity (no disease) RR 2.77 (1.70-4.52)

Coronary heart disease

Severity (no disease) RR 2.03 (1.39-2.15)

Golpe et al., 2020 Spain 539 Chronic heart failure

Hospitalization (no CHF)

n.s.

Coronary disease Hospitalization (no CD) n.s. Valvular heart disease

Hospitalization (no VHD)

n.s.

Atrial fibrillation Hospitalization (no AF) n.s. Hypertensive myocardiopathy

Hospitalization (no HM)

OR 14.0 (1.33-148.26)

Grasselli et al., 2020

Italy (Lombardy)

3988 Heart Disease Death n.s.


United States (PA)

563 Vascular disease (undefined)

Mortality (no vascular disease)

n.s.

Invasive Mechanical ventilation (no disease)

OR 3.18 (1.16-8.49)

Hashemi et al., 2020

United States (Mass)

363 Cardiac diseases Any severe outcome n.s.

Inciardi et al., 2020

Northern Italy 99 Cardiac disease Death RR 2.35 (1.08-5.09)

Kalligeros et al., 2020

United States (RI)

103 Heart disease ICU admission (no HD) n.s. Invasive mechanical ventilation (no HD)

aOR 3.41 (1.05-11.06)


Mexico 13842 CVD Death HR 1.3 (1.01-1.6)


United States (GA)

531 CVD Hospitalization n.s.


2491 CVD ICU admission (no disease)

n.s.

Mortality (no disease) aRR 1.28 (1.03-1.58) Ko et al., 2020 United States

(national) 5416 CAD Hospitalization (no

disease) n.s.


United Kingdom

800 CVD Mortality (no CVD) OR 2.32 (1.47 – 3.64)

Liu et al., 2020 Meta-analysis 10948 CAD/CVD Severe COVID-19 (no disease)

pOR 4.18 (2.87-6.09)


United States (NY)

200 Heart Failure (undefined)

Mortality (no disease) n.s.

CAD Mortality (no disease) n.s. Petrilli et al., 2020 United States

(NY) 5279 Heart Failure Hospitalization (no HF) OR 4.43 (2.59-8.04)

Regina et al., 2020

Switzerland 200 CAD Mechanical ventilation n.s.


Spain (Granada)

238 CVD Death (No disease) n.s.


522 CAD or CHF Death (no disease) n.s.


United States (MI)

463 CAD ICU admission (no disease)

n.s.


United States (NY)

3703 Heart Disease (CAD, AF, CHF)

IMV & Death (no disease)

n.s.


1827 CVD Hospitalization aOR 1.52 (1.16-2.0)



Association

Zheng et al., 2020 Meta-analysis 3027 CVD Critical/Death OR 5.19 (3.25-8.29) pOR: pooled Odds Ratio

Pulmonary Disease Like cardiovascular disease, lung disease is poorly defined in the included literature. The two major categories were chronic obstructive pulmonary disease (COPD) and asthma, and they appear to carry different risks of severe outcomes (Table 20). COPD appears to have a low strength association with severe COVID-19 outcomes (on balance, less than 2X increased odds of severity). Conversely, asthma does not carry significant risk of severe COVID-19 (on balance) and in some cases is shown to be a protective factor (Berumen et al., 2020). Schultze et al. (2020) found an increased odds of severity with asthma and inhaled corticosteroids, which may reflect an association between severe asthma and adverse outcomes, but this association has not yet been demonstrated in other studies. As with cardiovascular disease, there is a clear discrepancy between the low strength associations found by single primary studies and the moderate-high strength associations found by large meta-analytic studies. More research is needed to understand if pulmonary disease has a true association with severe COVID-19 outcomes or if this finding represents a systematic selection bias for severe disease in hospital-based studies.

Table 20. Association between lung diseases and severe outcomes of COVID-19. Low strength associations (not significant (n.s.), OR 2.5) are shaded red.


Association

Albitar et al., 2020 International 828 Chronic lung disease

Death n.s.

Atkins et al., 2020 United Kingdom

269070 Asthma Death (no disease) n.s. COPD Death (no disease) OR 1.91 (1.10-3.32)


Mexico 51633 COPD Death HR 1.40 (1.23-1.59)


Mexico 102875 Asthma Hospitalization (no asthma)

OR 0.7 (.061-0.8)

COPD Hospitalization (no COPD)

OR 3.63 (3.1-4.24)


Mexico 10544 COPD Hospitalization (None) OR 1.73 (1.20-2.50) Death (None) OR 1.68 (1.22-2.31)

Cummings et al., 2020

United States (NY)

257 COPD or interstitial lung disease

Death (patients without pulmonary disease)

HR 2.94 (1.48 – 5.84)


United Kingdom

20133 Chronic pulmonary disease

Death (No disease) HR 1.17 (1.09-1.27)


United States (CA)

442 Prior COPD or asthma

Severity (no disease) n.s.

Grasselli et al., 2020

Italy (Lombardy)

3988 COPD Death (no disease) HR 1.68 (1.28-2.19)

Hashemi et al., 2020

United States (Mass)

363 Pulmonary disorder Any severe outcome (no disease)

n.s.

Jain et al. 2020 Meta-analysis 1813 COPD ICU admission (no disease)

pOR 17.8 (6.56-48.2)

Kalligeros et al., 2020

United States (RI)

103 Lung disease (undefined)

ICU admission (no disease)

n.s.


Mexico 13842 COPD Mortality (no disease) HR 1.6 (1.3-1.9)


United States (GA)

531 Chronic respiratory disease (undefined)

Hospitalization (no disease)

n.s



Association


2491 Chronic lung disease (undefined)

ICU admission (no) aRR 1.17 (1.00-1.37) Mortality (no) aRR 1.31 (1.13-1.52)


5416 Asthma Hospitalization (no disease)

aRR 1.4 (1.1-1.7)

COPD Hospitalization (no disease)

n.s.


United Kingdom

800 COPD Mortality (no disease) n.s.

Liu et al., 2020 Meta-analysis 10948 Chronic pulmonary disease

Severe COVID-19 (no disease)

pOR 3.83 (2.15-6.80)


United States (NY)

200 COPD Mortality (no disease) n.s.


Spain (Granada)

238 Prior lung disease Death (no disease) n.s.

Salacup et al., 2020

United States (PA)

242 COPD and Asthma Death (No disease) n.s.

Schultze et al., 2020

United Kingdom

966461 COPD + Inhaled corticosteroid

Mortality aHR 1.38 (1.08-1.75)

Asthma + High dose ICS

Mortality aHR 1.52 (1.08 - 2.14)


522 COPD or Asthma Mortality (no disease) n.s.


United States (NY)

3703 COPD or Asthma IMV & Death n.s.


United States (NY)

7592 Asthma Death (no disease) n.s.


1827 COPD Hospitalization aOR 1.92 (1.35-2.72) Allergic rhinitis Hospitalization n.s.

Zheng et al., 2020 Meta-analysis 3027 Respiratory Disease

Critical/Death (no disease)

OR 5.15 (2.51-10.57)

Renal Disease Chronic kidney disease (CKD) was poorly defined in the literature. CKD appears to carry different risk for hospitalization and ICU admission compared to mortality (Table 21). On balance, there is no consistent increase in the odds or risk of death from COVID-19 associated with CKD. However, the risk of hospitalization is higher – studies report moderate strength associations between CKD and hospitalization or ICU admission. More research is needed to determine the nuances of risk associated with the different stages of CKD (including end-stage renal disease (ESRD)), kidney transplant, and acute kidney injury.

Table 21. Association between kidney disease and severe COVID-19 outcomes. Low strength associations (not significant (n.s.), OR 2.5) are shaded red.


Association

Albitar et al., 2020 International 828 CKD Death (no kidney disease)

n.s.


United States (NY)

1000 Renal disease Intubation (no renal disease)

n.s.

Death (no disease) HR 1.61 (1.06-2.43) Atkins et al., 2020 United

Kingdom 269070 CKD (undefined) Death (no disease) n.s.



Association


Mexico 51633 CKD (undefined) Death (No CKD) HR 1.99 (1.77-2.23)


Mexico 102875 CKD (undefined) Hospitalization (no CKD)

OR 4.24 (3.61-4.97)


Mexico 10544 CKD Hospitalization (None) OR 2.01 (1.33-3.04) Death (None) OR 1.44 (1.01-2.06)

Ciceri et al., 2020 Italy (Milan) 410 Chronic kidney failure (undefined)

Death (no kidney failure)

n.s.

Cummings et al., 2020

United States (NY)

257 CKD Death (no CKD) n.s.


United Kingdom

20133 CKD Death (No disease) HR 1.28 (1.18-1.39)


CKD (undefined) Severity (no CKD) RR 2.27 (1.55-3.32)


United States (PA)

563 CKD ≥ stage 3 Mortality (CKD < stage 3)

n.s.


Mexico 13842 Chronic kidney disease (undefined)

Mortality (no disease) HR 2.1 (1.6-2.6)


2491 Renal disease (undefined)

ICU admission (no) n.s. Mortality (no) aRR 1.33 (1.10-1.61)


5416 CKD (undefined) Hospitalization (no disease)

aRR 4.0 (3.0-5.2)


Spain 334 Multiple Myeloma + renal disease

Hospitalization (no comorbity)

aOR 4.6 (1.9-11.3)


United States (NY)

200 CKD or ESRD Mortality (no disease) n.s.


5279 CKD Hospitalization (No CKD)

OR 2.6 (1.89-3.61)


Spain (Granada)

238 CKD Death (no disease) n.s.

Rottoli et al. 2020 Italy (Bologna) 482 Moderate/severe renal disease

ICU admission (no disease)

HR 2.83 (1.46-5.49)

Death (no disease) n.s. Salacup et al., 2020

United States (PA)





United States (MI)

463 CKD ICU admission (no disease)

OR 2.0 (1.3-3.3)


United States (NY)

3703 CKD IMV & Death (no disease)

n.s.


United States (NY)

7592 CKD Death (no disease) OR 1.36 (1.01-1.83)

Other Conditions Cancer Cancer was considered as a variable in many of the included studies, however, was very poorly defined (often as just “malignancy” or “cancer”) and could be the subject of a full review on its own.

Three studies were identified that specifically investigated the association between cancer and severe outcomes of COVID-19: Lee et al., 2020; Martinez-Lopez et al., 2020; and Mehta et al., 2020. In a prospective cohort of 800 patients with active cancer who developed COVID-19, Lee (2020) showed that only male genital cancers and

Risk Factors for Severe Disease • 26 non-lymphoma haematological cancers had a low strength association with COVID-19 mortality in univariate analysis (less than 2X odds of mortality for both). Further, neither cancer stage nor treatment modality was associated with COVID-19 mortality in multivariate analysis (Lee et al., 2020).

Both Mehta (2020) and Martinez-Lopez (2020) show that in cancer patients, COVID-19 severity is more closely associated with comorbidity and age rather than cancer. In multiple myeloma patients (MM), specific features of MM such as monoclonal immunoglobulin G (IgG) treatment, renal disease, time since diagnosis or stem cell transplant were not associated with COVID-19 hospitalization, but other factors such as age, non-MM renal disease, and sex were (Martinez-Lopez et al, 2020). Likewise, Mehta et al. (2020) shows that the comorbidity score in cancer patients is associated with significantly increased odds of death (1.5X), compared to cancer patients with no comorbidity.

Inflammatory Bowel Disease Two studies were identified that describe the association between inflammatory bowel disease (IBD) and severe COVID-19 outcomes: Bezzio et al. (2020) and Taxonera et al. (2020). The evidence appears to be mixed for IBD. Bezzio (2020) describes a small prospective cohort (n=79) where active, untreated IBD is associated with 8.5X increased odds of death, and these odds increase with age and with additional comorbidity. Taxonera (2020), conversely, describes a retrospective case series where IBD was not found to have any significant association with COVID-19 mortality. More evidence is needed to determine the true risk to this population.

Pregnancy Few studies were identified that specifically examined the association between pregnancy and maternal risk of severe COVID-19 outcomes: Collin et al. (2020) and Martinez-Portilla et al. (2020). Carrillo-Vega (2020) examines pregnancy as a variable relating to mortality. An ad hoc search also identified a Morbidity and Mortality Weekly Report from the United States Centers for Disease Control and Prevention that calculated measures of association for maternal outcomes (Ellington et al., 2020). No studies were identified that examined the odds or risk to the developing fetus or the risk of pregnancy loss.

In the studies that include a measure of association, both describe a high strength association between severe maternal outcomes from COVID-19 (Table 22). Collin (2020) reported on confirmed COVID-19 cases in pregnant women admitted to Swedish ICUs using a comparator of nonpregnant women of similar age, Pregnant or postpartum women had a 4X higher risk of intubation (0.014% versus 0.003%) and a 5.4X higher risk of requiring intensive care than non-pregnant women (0.007% versus 0.002%). These findings are very similar to those of Ellington (2020), who found a high strength association between pregnancy and risk of hospitalization although hospitalization could be for non COVID causes (5.4X higher risk compared to non-pregnant women) and a moderate strength association between pregnancy and ICU admission/mechanical ventilation (1.5X and 1.7X higher risk, respectively) (Ellington et al., 2020). Martinez-Portilla (2020) suggested that the odds of COVID-19 mortality is increased in pregnant women as maternal age increases above 35 years (7.7X) or the mother has a co-occurring morbidity (6.1X) in a description of 124 pregnant women with COVID-19, with 5 of 7 fatalities in women with comorbid health conditions. Carrillo-Vega (2020) described 9946 patients, of which 48 were pregnant and reported 3.6X higher odds of maternal mortality in pregnant compared to non-pregnant women, although noted that 4/5 of the fatal cases were in women with comorbidities. Conversely, Ellington (2020) did not find a significant association between pregnancy and maternal mortality, with an absolute risk of mortality among both pregnant and non-pregnant women of 0.2%. In both Martinez-Portilla (2020) and Collin (2020), the 95% confidence interval is very wide, limiting the reliability of these findings.

Table 22. Association between pregnancy and severe COVID-19 outcomes. Low strength associations (not significant (n.s.), OR 2.5) are shaded red.


Reference Jurisdiction Study Size Condition Outcome (comparator)

Association


Mexico 10544 people, 48 pregnant, 5 deaths

Pregnancy Death (not pregnant) OR 3.56 (1.17-10.80)

Collin et al., 2020 (univariate association)

Sweden 53 Pregnant or postpartum

Intensive care (non-pregnant)

RR 5.39 (2.89-10.08)

Invasive ventilation (non-pregnant)

RR 4.00 (1.75-9.14)

Ellington et al., 2020

United States (national)

91412 women age 15-44, 8207 pregnant

Pregnant Hospitalization (non-pregnant, includes non COVID hospitalization)

aRR 5.4 (5.1-5.6)

ICU admission (non-pregnant)

aRR 1.5 (1.2-2.4)

Mechanical ventilation (non-pregnant)

aRR 1.7 (1.2-2.4)

Death (non-pregnant)

n.s.

Martinez-Portilla et al., 2020 (Univariate association)

Mexico 1241 (7 deaths)

Pregnancy + Age >35 years

Mortality (Age


Authorship and Committee Members This report was written by Rachael Erdmann and scientifically reviewed by Andrew McRae, Elizabeth MacKay, Anne Hicks, Colleen Norris, Vineet Saini, Lynora Saxinger and Colin Birch. The full Scientific Advisory Group was involved in discussion and revisions of the document: Braden Manns (co-chair), Lynora Saxinger (co-chair), John Conly, Alexander Doroshenko, Nelson Lee, Elizabeth MacKay, Andrew McRae, James Talbot, Shelley Duggan, Jeremy Slobodan, Brandie Walker, and Nathan Zelyas.

© 2020, Alberta Health Services, COVID-19 Scientific Advisory Group

This copyright work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivative 4.0 International license. You are free to copy and distribute the work including in other media and formats for non-commercial purposes, as long as you attribute the work to Alberta Health Services, do not adapt the work, and abide by the other licence terms. To view a copy of this licence, see https://creativecommons.org/licenses/by-nc-nd/4.0/.

The licence does not apply to AHS trademarks, logos or content for which Alberta Health Services is not the copyright owner. Disclaimer: This material is intended for general information only and is provided on an "as is", "where is" basis. Although reasonable efforts were made to confirm the accuracy of the information, Alberta Health Services does not make any representation or warranty, express, implied or statutory, as to the accuracy, reliability, completeness, applicability or fitness for a particular purpose of such information. This material is not a substitute for the advice of a qualified health professional. Alberta Health Services expressly disclaims all liability for the use of these materials, and for any claims, actions, demands or suits arising from such use.

Date question received by advisory group: July 21, 2020

Date report submitted to committee: August 13, 2020

Date of first assessment: August 21, 2020

(If applicable) Date of re-assessment:

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Appendix

List of Abbreviations ACEI: angiotensin-converting enzyme inhibitors

AF: atrial fibrillation

aHR: adjusted hazard ratio

AHS: Alberta Health Services

aOR: adjusted odds ratio

ARB: angiotensin receptor blockers

aRR: adjusted risk ratio

BMI: Body Mass Index

CA: California

CAD: coronary artery disease

CHD: chronic heart disease

CHF: congestive heart failure

CKD: Chronic Kidney Disease

COPD: Chronic Obstructive Pulmonary Disease

COVID-19: Coronavirus Disease-2019

CVD: cardiovascular disease

ESRD: end-stage renal disease

GA: Georgia

HR: hazard ratio

IBD: Inflammatory Bowel Disease

ICS: inhaled corticosteroid

ICU: Intensive Care Unit

IL: Illinois

IMV: Invasive Mechanical Ventilation

KRS: Knowledge Resource Services

LA: Louisiana

Risk Factors for Severe Disease • 30 Mass: Massachusetts

MI: Michigan

MI: myocardial infarction

MM: multiple myeloma

MV: Mechanical Ventilation

n.s.: Not Significant

NY: New York

OR: odds ratio

PA: Pennsylvania

pOR: Pooled Odds Ratio

RI: Rhode Island

RR: risk ratio

SAG: Scientific Advisory Group

SLI: Social Lag Index

UK: United Kingdom

Methods Literature Search A literature search was conducted by Lauren Seal from Knowledge Resources Services (KRS) within the Knowledge Management Department of Alberta Health Services. KRS searched databases for articles published in 2020 and included: Medline, CINAHL, PubMed, LitCOVID, and medRxiv Preprints. The search strategy was expanded from the search used for the initial Rapid Evidence Brief to include specific pre-existing conditions and determinants of health. A second, short search was performed to identify studies specifically pertaining to the association between asthma and severe outcomes from COVID-19. Both search strategies are appended below. Briefly, the strategies involved combinations of keywords and subject headings including:

- Pre-existing KRS COVID-19 search filter - Mortality or artificial respiration or mechanical ventilation or critical care or hospitalization or ICU

admission - Age factors or COPD or Asthma or heart diseases or renal insufficiency or diabetes mellitus or obesity or

hypertension or blood pressure or gastrointestinal disease or nervous system diseases or liver diseases or thyroid diseases or pregnancy or sex

Articles identified by KRS in their search were initially screened by title against the inclusion/exclusion criteria listed in Table 23 below. 321 articles were identified by KRS with references and abstracts provided for further review. 165 studies were excluded based on the title and abstract. 92 studies were excluded following full-text review, and two studies were identified by ad hoc searching. 66 studies were included in the final narrative synthesis.

Risk Factors for Severe Disease • 31 Table 23. Inclusion and exclusion criteria for results of the literature search

Inclusion Criteria Exclusion Criteria - Any population - Epidemiological studies describing

association between age, medical condition, biological determinants, lifestyle factors and severe outcomes of COVID

- Measure of association is calculated - In primary studies, association is derived

from European, North American or ANZAC populations

- Multivariate or univariate analysis - Observational studies, Systematic

reviews, Meta-analyses, grey literature, Preprints

- Article is not from a credible source - Article does not have a clear research

question or issue - Presented data/evidence is not sufficient

to address the research questions - No measure of association calculated - Hypotheses regarding comorbidity and

COVID - Therapeutic implications of comorbidity

and COVID - Association between lab values or COVID

symptoms and disease severity - Prevalence study - In primary studies, association is derived

from Asian, South American, or African populations

- Articles on patient management - Commentary, Case reports, Small case

series (n




Table 24. Evidence Extraction Table of Included Studies.

Reference Jurisdiction Type of Study Characteristic Outcome (Comparator) Associated Risk Model notes: Al-Salameh, A., Lanoix, J.-P., Bennis, Y., Andrejak, C., Brochot, E., Deschasse, G., Dupont, H., Goeb, V., Jaureguy, M., Lion, S., Maizel, J., Moyet, J., Vaysse, B., Desailloud, R., Ganry, O., Schmit, J.-L., & Lalau, J.-D. (2020). Characteristics and outcomes of COVID-19 in hospitalized patients with and without diabetes. Diabetes/Metabolism Research and Reviews, e3388

France Prospective cohort study of adult patients with lab-confirmed COVID-19 (n=326).

Diabetes ICU admission (no diabetes)

OR 2.06 (1.09-3.92)

Multivariate Cox proportional hazards model (factors include age, sex, BMI, cardiac disease, and serum C-reactive protein). BMI was not a significant factor in the model.

Death n.s.

Albitar, O., Ballouze, R., Ooi, J. P., & Sheikh Ghadzi, S. M. (2020). Risk factors for mortality among COVID-19 patients. Diabetes Research and Clinical Practice, 166, 108293

n/a – International open source data set

Retrospective cross-sectional study (n=828)

Age ≥ 65 years Death (< 65 years) aOR 1.08 (1.06-10.9)

Multivariable logistic regression

Sex (male) Death (Female) aOR 1.6 (1.0-2.6) Hypertension Death (Non-hypertensive) aOR 3.6 (1.7-7.5) Diabetes mellitus Death (Non-diabetic) aOR 12.2 (4.1-

36.3) Chronic lung diseases (undefined)

Death (no lung disease) n.s.

Chronic kidney disease (undefined)

Death (no kidney disease)

n.s.

Cardiovascular disease (undefined)

Death (no cardiovascular disease)

n.s.

Alqahtani, J. S., Oyelade, T., Aldhahir, A. M., Alghamdi, S. M., Almehmadi, M., Alqahtani, A. S., Quaderi, S., Mandal, S., & Hurst, J. R. (2020). Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis. PloS One, 15(5).

n/a Systematic review and meta-analysis (n= 2473)

COPD Death (no COPD) RR 1.88 (1.4-2.4) Calculated risk ratio from prevalence estimates

Current smoker Severe complications (never or former smoker)

RR 1.45 (1.03-2.04)

Argenziano, M. G., Bruce, S. L., Slater, C. L., Tiao, J. R., Baldwin, M. R., Barr, R. G., . . . Chen, R. (2020). Characterization and clinical

United States (New York) – New York

Retrospective descriptive study of first

Numeric age (undefined) Intubation (younger age) n.s. Multivariate Cox proportional hazard model

Death (younger age) HR 1.07 (1.05-1.08)


Reference Jurisdiction Type of Study Characteristic Outcome (Comparator) Associated Risk Model notes: course of 1000 patients with coronavirus disease 2019 in new york: Retrospective case series. Bmj, 369, m1996.

Presbyterian / Columbia University

1000 hospitalized patients

Female Intubation (male) HR 0.71 (0.54-0.95)

Death (male) n.s. BMI (undefined) Intubation (lower BMI) n.s.

Death (lower BMI) HR 1.02 (1.0-1.05) Current or former smoker

Intubation or death (never smoker)

n.s.

Coronary artery disease Intubation or death (no CAD)

n.s.

Congestive heart failure Intubation or death (no CHD)

n.s.

Stroke Intubation or death (no stroke)

n.s.

Diabetes mellitus (undefined)

Intubation or death (no diabetes)

n.s.

Hypertension Intubation (no hypertension)

n.s.

Death (no hypertension) HR 1.59 (1.1-2.3) Cirrhosis Intubation or death (no

cirrhosis) n.s

HIV Intubation (no HIV) n.s. Death (no HIV) HR 2.47 (1.05-

5.86) Inflammatory Bowel Disease

Intubation or death (no IBD)

n.s.

Pulmonary disease (undefined)

Intubation or death (no pulmonary disease)

n.s.

Renal Disease (undefined)

Intubation (no renal disease)

n.s.

Death (no renal disease) HR 1.61 (1.06-2.43)

Viral hepatitis Intubation or death (no hepatitis)

n.s.

Cancer (undefined) Intubation or death (no cancer)

n.s.


Reference Jurisdiction Type of Study Characteristic Outcome (Comparator) Associated Risk Model notes: Atkins, J. L., Masoli, J., Delgado, J., Pilling, L. C., Kuo, C. L., Kuchel, G. A., & Melzer, D. (2020). Preexisting Comorbidities Predicting COVID-19 and Mortality in the UK Biobank Community Cohort. The journals of gerontology. Series A, Biological sciences and medical sciences, glaa183.

United Kingdom Retrospective cohort study (Cohort n=269070; COVID+ n=507; Died n=141)

Age 70-74 Death (65-69 yrs) n.s. Multivariate Logistic regression analysis. Models adjusted for age (5 year bands), sex, ethnicity, education, geography, and comorbidities

Age 75-79 Death (65-69 yrs) OR 2.16 (1.27-3.65)

Age 80+ Death (65-69 yrs) OR 2.65 (1.33-5.29)

Male Death (Female) OR 2.12 (1.45-3.09)

Black Death (White) OR 2.6 (1.09-6.19) South Asian Death (White) n.s. No educational qualification

Death (degree attained) OR 1.82 (1.1-2.99)

Chronic Heart Disease (Undefined)

Death (no history of disease)

n.s.

Atrial fibrillation Death (no history of disease)

n.s.

Stroke Death (no history of disease)

n.s.

Hypertension Death (no history of disease)

n.s.

Diabetes Type II Death (no history of disease)

OR 3.11 (2.06-4.71)

Chronic Kidney disease (undefined)

Death (no history of disease)

n.s.

Depression Death (no history of disease)

OR 1.78 (1.07-2.96)

Dementia Death (no history of disease)

OR 7.30 (3.28-16.21)

Asthma Death (no history of disease)

n.s.

COPD Death (no history of disease)

OR 1.91 (1.10-3.32)

Osteoarthritis Death (no history of disease)

n.s.

Osteoporosis Death (no history of disease)

n.s.


Reference Jurisdiction Type of Study Characteristic Outcome (Comparator) Associated Risk Model notes: Bello-Chavolla, O. Y., Bahena-López, J. P., Antonio-Villa, N. E., Vargas-Vázquez, A., González-Díaz, A., Márquez-Salinas, A., . . . Aguilar-Salinas, C. A. (2020a). Predicting mortality due to SARS-CoV-2: A mechanistic score relating obesity and diabetes to COVID-19 outcomes in mexico. The Journal of Clinical Endocrinology and Metabolism, doi:10.1210/clinem/dgaa346

Mexico Retrospective analysis (COVID+ n= 51633)

Age ≥ 65 years Death (Age < 65 years) HR 2.02 (1.89-2.16)

Cox Proportional risk model (Multivariate)

Diabetes mellitus (undefined)

Death (No diabetes) HR 1.34 (1.26-1.43)

Diabetes * Age


Reference Jurisdiction Type of Study Characteristic Outcome (Comparator) Associated Risk Model notes: infection and hospitalization by Covid-19 in Mexico a case-control study. Medrxiv, 1–26

Age 61-70 years Hospitalization (≤ 20 yrs) OR 8.97 (7.39-10.88)

Age > 70 years Hospitalization (≤ 20 yrs) OR 11.6 (9.48-14.19)

Diabetes (undefined) Hospitalization (no diabetes)

OR 3.69 (3.48-3.93)

Obesity (undefined) Hospitalization (no obesity)

OR 1.47 (1.39-1.55)

Hypertension Hospitalization (no hypertension)

OR 2.79 (2.64-2.95)

Asthma Hospitalization (no asthma)

OR 0.7 (.061-0.8)

COPD Hospitalization (no COPD)

OR 3.63 (3.1-4.24)

CKD (undefined) Hospitalization (no CKD) OR 4.24 (3.61-4.97)

Bezzio, C., Saibeni, S., Variola, A., Allocca, M., Massari, A., Gerardi, V., . . . Fiorino, G. (2020). Outcomes of COVID-19 in 79 patients with IBD in italy: An IG-IBD study. Gut, 69(7), 1213-1217. doi:10.1136/gutjnl-2020-321411

Italy Prospective cohort for confirmed IBD and COVID-19 (n= 79)

Age < 65 years Death (Age 1 Death (CCI score =1) OR 16.66 (1.8-

153.9) Active IBD Death (Treated IBD) OR 8.45 (1.26 –

56.56) Ulcerative Colitis diagnosis

Death (No UC) n.s.

Corticosteroid treatment Death (no steroids) n.s. Anti-Tumor Necrosis Factor

Death (no anti-TNF) n.s.

Notes: Pneumonia required hospitalization in 61% of patients. IBD treatments were not associated with either pneumonia or death.

Cariou, B., Hadjadj, S., Wargny, M., Pichelin, M., Al-Salameh, A., Allix, I., Amadou, C., Arnault, G., Baudoux, F., Bauduceau, B., Borot, S., Bourgeon-Ghittori, M., Bourron, O., Boutoille, D., Cazenave-Roblot, F., Chaumeil, C., Cosson, E., Coudol, S., Darmon, P., … Gourdy, P. (2020). Phenotypic characteristics

France CORONADO prospective cohort study of patients with type 1 or 2 diabetes (n=1317)

Age (+1 SD) Death (mean age) OR 2.39 (1.67-3.42)

Multivariable logistic regression (fully adjusted) Female Death (male) n.s.

BMI (+1 SD) Death (mean BMI) n.s. Hypertension Death (no hypertension) n.s. Microvascular diabetic complications

Death (no complications) n.s.


Reference Jurisdiction Type of Study Characteristic Outcome (Comparator) Associated Risk Model notes: and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia, 63(8), 1500–1515

Macrovascular diabetic complications

Death (no complications) OR 2.26 (1.25-4.08)

Heart failure (undefined) Death (no heart failure) n.s. Active cancer (undefined)

Death (no cancer) n.s.

Notes: Univariate analysis suggests that odds of death are significant in males and those with high BMI (undefined). BMI loses significance when applied to a multivariate model.

Carrillo-Vega, M. F., Salinas-Escudero, G., Garcia-Peña, C., Gutierrez-Robledo, L. M., & Parra-Rodriguez, L. (2020). Early estimation of the risk factors for hospitalisation and mortality by COVID-19 in Mexico. MedRxiv, 2020.05.11.20098145.

Mexico Retrospective cohort study (n= 10544)

Male sex Hospitalisation (female) OR 1.54 (1.37-1.74) Multivariable logistic regression Death (female) OR 1.53 (1.30-1.81)

Age 50-74 years Hospitalisation (25-49 yrs)

OR 2.05 (1.81-2.32)

Death (25-49 yrs) OR 1.96 (1.63-2.34) Age ≥ 75 years Hospitalisation (25-49

yrs) OR 3.84 (2.90-5.10)

Death (25-49 yrs) OR 3.74 (2.80-4.98) Chronic Kidney disease Hospitalisation (None) OR 2.01 (1.33-3.04)

Death (None) OR 1.44 (1.01-2.06) COPD Hospitalisation (None) OR 1.73 (1.20-2.50)

Death (None) OR 1.68 (1.22-2.31) Diabetes + Hypertension + Obesity

Hospitalisation (None) OR 1.85 (1.34-2.56)

Death (None) OR 2.10 (1.50-2.93)

Diabetes + hypertension Hospitalisation (None) OR 2.60 (2.04-3.31) Death (None) OR 1.92 (1.48-2.49)

Diabetes + obesity Hospitalisation (None) OR 1.78 (1.22-2.59) Death (None) OR 2.06 (1.35-3.12)

Hypertension + obesity Hospitalisation (None) OR 1.65 (1.24-2.19) Death (None) OR 1.88 (1.33-2.65)

Hypertension Hospitalisation (None) OR 1.54 (1.26-1.88) Death (None) OR 1.49 (1.15-1.92)

Obesity (undefined) Hospitalisation (None) OR 1.64 (1.37-1.95) Death (None) OR 1.72 (1.35-2.26)

Diabetes Hospitalisation (None) OR 2.14 (1.70-2.69) Death (None) OR 1.50 (1.13-1.98)

Pregnancy Death (not pregnant) OR 3.56 (1.17-10.80)


Reference Jurisdiction Type of Study Characteristic Outcome (Comparator) Associated Risk Model notes: Ciceri, F., Castagna, A., Rovere-Querini, P., De Cobelli, F., Ruggieri, A., Galli, L., Conte, C.,… Zangrillo, A. (2020). Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy. Clin Immunol. 217 (108509).

Italy (Milan) Prospective cohort of hospitalized patients (n=410)

Age > 65 years Death (Age


Reference Jurisdiction Type of Study Characteristic Outcome (Comparator) Associated Risk Model notes: CKD nor BMI were significantly associated with mortality in either univariate or multivariate analysis.

Denova-Gutierrez, E., Lopez-Gatell, H., Alomia-Zegarra, J. L., Lopez-Ridaura, R., Zaragoza-Jimenez, C. A., Dyer-Leal, D. D., Cortes-Alcala, R., Villa-Reyes, T., Gutierrez-Vargas, R.

Documents

COVID-19 Scientific Advisory Group Rapid Evidence Report · 2020. 8. 21. · COVID-19 Scientific Advisory Group Topic: What risk factors (such as age, medical conditions, or lifestyle