key: cord-0851008-m2d82923
authors: Gates, M.; Pillay, J.; Wingert, A.; Guitard, S.; Rahman, S.; Zakher, B.; Gates, A.; Hartling, L.
title: Risk factors associated with severe outcomes of COVID-19: An updated rapid review to inform national guidance on vaccine prioritization in Canada
date: 2021-04-26
journal: nan
DOI: 10.1101/2021.04.23.21256014
sha: ca7500300bb50a6c74062eb79a9ed85d9a1b9c51
doc_id: 851008
cord_uid: m2d82923

Background: To inform vaccine prioritization guidance by the National Advisory Committee on Immunization (NACI), we reviewed evidence on the magnitude of association between risk factors and severe outcomes of COVID-19. Methods: We updated our existing review by searching online databases and websites for cohort studies providing multivariate adjusted associations. One author screened studies and extracted data. Two authors estimated the magnitude of association between exposures and outcomes as little-to-no (odds, risk, or hazard ratio <2.0, or >0.50 for reduction), large (2.0-3.9, or 0.50-0.26 for reduction), or very large (>=4.0, or <=0.25 for reduction), and rated the evidence certainty using GRADE. Results: Of 7,819 unique records we included 111 reports. There is probably (moderate certainty) at least a large increase in mortality from COVID-19 among people aged 60-69 vs. <60 years (11 studies, n=517,217), with 2+ vs. no comorbidities (4 studies, n=189,608), and for people with (vs. without): Down syndrome (1 study, n>8 million), type 1 and 2 diabetes (1 study, n>8 million), end-stage kidney disease (1 study, n>8 million), epilepsy (1 study, n>8 million), motor neuron disease, multiple sclerosis, myasthenia gravis, or Huntingtons disease (as a grouping; 1 study, n>8 million). The magnitude of association with mortality is probably very large for Down syndrome and may (low certainty) be very large for age 60-69 years, and diabetes. There is probably little-to-no increase in severe outcomes with several cardiovascular and respiratory conditions, and for adult males vs. females. Interpretation: Future research should focus on risk factors where evidence is low quality (e.g., social factors) or non-existent (e.g., rare conditions), the pediatric population, combinations of comorbidities that may increase risk, and long-term outcomes. Systematic review registration: PROSPERO #CRD42021230185.

The novel coronavirus disease 2019 (COVID-19) became a worldwide public health concern in early 2020 [1] . About 20% of affected people will experience severe disease (e.g., requiring hospitalization); some may have long-lasting medical complications [2] . In late 2020, Health Canada approved two vaccines for the prevention of COVID-19 (Pfizer-BioNTech and Moderna); this has been followed by the approval of others and continued review of emerging candidates [3] . As anticipated, vaccine distribution has been constrained by logistical challenges and limited supply [4] [5] [6] , necessitating prioritization of populations for vaccination [5, 6] .

The National Advisory Committee on Immunization (NACI) developed preliminary vaccine prioritization guidance in late 2020 "for the efficient, effective and equitable allocation of safe, efficacious severe acute respiratory syndrome children in any of the aforementioned populations. Canadian reports of any design with any analysis type were eligible.

For social risk factors, we included only Canadian reports (considered as most relevant by NACI).

We applied criteria to include only the most informative, good quality studies. Studies needed to take place in Organization for Economic Cooperation and Development (OECD) countries and include ≥1,000 participants (i.e., sufficiently powered for multivariate adjustment). Adjustment by age and sex was required in all studies, except Canadian reports. Findings for age and/or sex required adjustment for at least one pre-existing condition, and findings for most pre-existing conditions required adjustment for body mass index (BMI). When no primary studies were located on a risk factor of high relevance to NACI, we included systematic reviews with broader selection criteria. websites suggested by NACI (6 January -3 February, 2021). We exported records to Endnote X9 (Clarivate Analytics, Philadelphia, PA), removed duplicates and pre-prints, then uploaded the records to Covidence (https://www.covidence.org/). After piloting, a single experienced reviewer screened each record by title and abstract, then by full text. A second reviewer was consulted as needed.

Following screening, we found no studies meeting our criteria for children, asplenia/splenic dysfunction, cystic fibrosis, sickle cell disease, β-thalassemia, and learning disability (potentially important based on inclusion in priority lists from other jurisdictions [15] [16] [17] [18] ). To locate evidence for these, we scanned all studies excluded based on sample size (<1,000 participants), preprints, and systematic reviews that we had located during our scoping exercises (September, 2020) using Smart Searches in Endnote. On 18 February 2021, we conducted targeted searches in Ovid Medline® ALL 1946-for studies and reviews on these risk factors.

After piloting, a single reviewer extracted data from each study into Excel (v. 2016; Microsoft Corporation, Redmond, WA): study and population characteristics, exposures, covariates, outcomes and their definitions, findings for multivariate associations. We held regular team meetings to troubleshoot and ensure consistency. Because we attempted to include only good quality studies, we did not formally assess their quality, but recorded potential risk of bias concerns (Appendix 2) for consideration during certainty of evidence assessments.

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Appendix 2 details our approach to synthesis and drawing conclusions. Results from the Canadian studies, none of which had sufficiently adjusted analysis, were not included in the main synthesis and are reported separately. We did not pool findings statistically due to large heterogeneity in comparisons and measures of association, and at least some overlap in populations across studies. Instead, two reviewers reached consensus on a best estimate of the magnitude of association for each outcome (based on adjusted odds [aOR], risk, or hazard ratios): little-to-no (<2.0, or >0.5 for reduction), large (2.0-3.9, or 0.5-0.26 for reduction), or very large (≥4.0, or ≤0.25 for reduction). Two reviewers assessed the certainty of evidence for each exposure-outcome association, informed by elements of the Grading of Recommendations, Assessment, Development and Evaluations approach [19] .

Ethics approval was not required.

Of 7,819 unique records identified, we included 111 reports (Figure 1 ) . Full text exclusions are listed at [https://doi.org/10.7939/DVN/VDELOG]. Of the included studies, two in children did not meet all of our pre-specified eligibility criteria, but were included since no studies meeting all criteria were found; one had <1,000 participants [32] and both were unadjusted for BMI [32, 64] . We included one systematic review of case series for β-thalassemia [119] .

No studies or reviews were located with relevant findings for asplenia/splenic dysfunction, cystic fibrosis, sickle cell disease, or learning disability. No study reported on long-term outcomes. Table 2 shows a summary of the characteristics of the studies presenting multivariate adjusted findings that were included in the main synthesis (n=102) ; full details by study, including nine Canadian reports [122] [123] [124] [125] [126] [127] [128] [129] [130] , are in Appendix 3. The studies contributing multivariate associations originated primarily from the United States (n=45) and the United Kingdom (n=15), and included more than 74 million participants (median 5,247; range 34 to 61, 414, 470) .

Based on stakeholder input, we considered people with confirmed COVID-19 to be the population of highest relevance, and focus on these in our presentation of findings. When no data were available from the COVID-19 population for a risk factor-outcome comparison, we relied on findings from the general population. Table 3 The certainty of evidence was moderate for at least a large increase in mortality from COVID-19 for people aged 60-69 years versus <60 years (11 studies, n=517,217) [24, 48, 63, 68, 71, 84, 92, 93, 98, 101, 106, 113] , people with two or more versus no comorbidities (4 studies, n=189,608) [48, 59, 101, 105] Huntington's disease (as a grouping; 1 study, n>8 million) [35] . The magnitude of association with mortality is probably (moderate certainty) very large for Down syndrome, and may (low certainty) be very large for age 60-69 years, and diabetes. We located no evidence on the combination of conditions that would place people with two or more comorbidities at increased risk.

The certainty of evidence was low for a large increase in mortality or hospitalization among: people with cerebral palsy (1 study, n>8 million); major psychiatric disorder (schizophrenia, schizoaffective disorder, or bipolar disorder, with drug use for the condition in the past 6 months; 1 study, n=11,122) [ [77, 95] . The magnitude of association with mortality may (low certainty) be very large for recent chemotherapy. There was moderate certainty for a large increase in hospitalization with previous cerebrovascular accident (2 studies, n=12,376) [49, 115] . There was evidence of low certainty for a large reduction in hospitalization for children (0-19 years) versus adults aged 50-59 years (1 study, n=2,199) [105] , and a large increase in hospitalization for children with (versus without): obesity (1 study, n=21,116) [82] ; hypertension (1 study, n=21,116) [82] ; immunodeficiency (1 study, n=21,116) [82] . There was low certainty for a large increase in intensive care unit admission for children: aged <1 month versus >1 month (1 study, n=582) [50] ; who are male versus female (1 study, n=582) [50] ; with (versus without) pre-existing medical conditions (1 study, n=582) [50] . There were several risk factors with moderate certainty evidence for little-to-no association with increased severity of COVID-19, for example many pre-existing conditions (notably several cardiovascular and respiratory conditions), and for adult males versus females (Appendix 2). Table 4 shows the risk factors identified in Canadian reports and potential associations with severe outcomes of COVID-19. All data collected from these studies are in Appendix 2. This evidence was used primarily to draw conclusions about social factors, and was often descriptive and lacking adjustment for important covariates. These studies showed the potential for a large increase in mortality among people living in long-term care (6 reports, n≈2 million) [122, 123, 125, . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 26, 2021. ; https://doi.org/10.1101/2021.04.23.21256014 doi: medRxiv preprint 127, 128] , visible minority groups (mainly South Asian, Chinese, Black, Filipino, Latin American, Arab, Southeast Asian, West Asian, Korean, Japanese; 1 report, n=8,796) [129] , and people living in the general population (off-reserve) versus First Nations people living on-reserve (1 report, n=9,715) [124] .

This review provides a methodologically rigorous synthesis of a large volume of emerging evidence on factors associated with severe outcomes of COVID-19. There is now strong (moderate certainty) evidence of at least a large increase in mortality from COVID-19 among people aged 60 to 69 versus <60 years (and over 70 years from our previous review [117] ), people having two or more versus no comorbidities, and for people affected by (versus unaffected): Down syndrome; type 1 and type 2 diabetes; end-stage kidney disease; epilepsy; motor neuron disease, multiple sclerosis, myasthenia gravis, or Huntington's disease.

Our earlier review suggested a potentially large increase in severe outcomes among males versus females, and for people with some pre-existing conditions (heart failure, dementia, liver disease) [10]. The current evidence no longer supports this increased risk, underscoring the importance of interpreting low certainty evidence cautiously, and of continually reviewing emerging data to support vaccine prioritization guidance. There is now relatively strong evidence for little-to-no increase in severe outcomes for several pre-existing diseases, notably many cardiovascular and respiratory conditions. In contrast, many jurisdictions have identified people with these conditions as priorities for vaccination [15] [16] [17] [18] . The reason for this is not fully clear, because the evidence on which prioritization decisions are made is often not publically available, and such decisions are informed by multiple considerations (e.g., local epidemiology, ethics, risk-benefit analyses, vaccine characteristics and availability [5, 6, 131] ) and varying levels of evidence.

A large reliance on unadjusted data may provide some explanation [132] . The data synthesized within this review have the advantage of accounting for the impact of multiple co-existing conditions, social and demographic factors. For example, in a large study (n=418,794) of the general population in the United Kingdom [94] , a large increase in hospitalization among people with heart failure (OR 2.24) and chronic obstructive pulmonary disease (OR 2.67) was observed. Following adjustment for age, sex, social factors, BMI, and other chronic conditions, these associations were substantially attenuated to the range of little-to-no association (aOR 1.09 and 1.51, respectively) [94] . We observed similar relationships in other studies. The thresholds of magnitude used to define 'large' and 'very large' increases in severe outcomes may also impact the conditions prioritized. Finally, there are some rare conditions (e.g., thalassemia, splenic dysfunction) for which to our knowledge, no large and well-adjusted studies have been published. In these cases, governing bodies may need to rely on evidence available for other infectious diseases, or from smaller cohorts suggesting the potential for increased risk [18, [133] [134] [135] [136] .

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The findings of this review, among other considerations, have informed NACI's vaccine prioritization guidance. Emerging data should continue to be synthesized to improve on the certainty of evidence for some populations and outcomes.

Though children seem to be at reduced risk of severe outcomes of COVID-19 compared to adults [137] , there are few well-adjusted analyses available. Further data from large, high quality studies among the pediatric population may help to inform future guidance. As we did not locate data to inform the combination of comorbidities that may place a person at increased risk of severe outcomes, a focus on this in future research would be valuable. Information from the development of risk prediction models may also provide insight [138] . Finally, while we looked for studies examining a range of factors based on the "P 2 ROGRESS And Other Factors" framework, the majority of studies focused on medical comorbidities. High quality research on P 2 ROGRESS And Other Factors would allow for a more nuanced approach to optimize vaccine rollout [131] .

Because we used a rapid approach, there is a small possibility of undetected errors in study selection or data extraction.

We mitigated this through piloting and engaging experienced reviewers. Though the findings are most applicable to OECD countries, we often relied on data largely from the United States and other countries without universal healthcare systems. We located no evidence relevant to long-term outcomes.

There is strong evidence to support at least a large increase in mortality from COVID-19 among older adults aged 60 to 69 years versus <60 years; people having two or more versus no comorbidities; and for people affected by Down syndrome, type 1 and 2 diabetes, end-stage kidney disease, epilepsy, and motor neuron disease, multiple sclerosis, myasthenia gravis, or Huntington's disease (as a grouping). Future research should focus on risk factors where evidence remains limited (no studies) or of low quality, the pediatric population, combinations of comorbidities that may increase risk, and long-term outcomes.

We thank Kelsey Young, Kelly Farrah, Shainoor Ismail, and Matthew Tunis from the NACI Secretariat for expert input into is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 26, 2021. ; https://doi.org/10.1101/2021.04.23.21256014 doi: medRxiv preprint CONTRIBUTOR'S STATEMENT MG contributed to the conception and design of the work, selection of studies, data extraction, analysis and interpretation of data, and drafted the initial version of the manuscript. JP contributed to the conception and design of the work, analysis and interpretation of data, and revised versions of the manuscript. AW, SG, SR, BZ, and AG contributed to the selection of studies, data extraction, organizing data for analysis, and revised versions of the manuscript. LH contributed to the conception and design of the work, methodological oversight, interpretation of findings, and revised versions of the manuscript. All authors approved of the final version of the manuscript submitted and agree to be accountable for all aspects of the work.

The funders had no role in the conduct of the study nor decision to submit for publication.

The data pertaining to the conclusions are available on reasonable request using the following link:

https://doi.org/10.7939/DVN/VDELOG.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) Factors experienced differently or to a different extent (e.g., different age group). When included, systematic reviews did not require a comparator.

Exclude: Variations in disease severity within the pre-existing disease/condition or disability category (i.e., only interested in presence/absence of this risk factor); studies without a comparator.

Include: Epidemiologic or analytic data from Canadian reports; from all other studies, magnitude of association (based on multivariate analysis adjusting for at minimum age and sex) * between the exposure and any of hospitalization; in-hospital length of stay; ICU admission; ICU length of stay; mechanical ventilation; mortality (all-cause or case fatality); severe disease (composite outcomes as defined by study authors); need for rehabilitation; stroke; kidney, liver, or cardiac injury; generic functionality and/or disability (composite scores of validated scales); generic quality of life (composite scores of validated scales). * Age and sex needed to be adjusted for at least one pre-existing condition. Pre-existing conditions (except neurologic, mental health, frailty) needed to be adjusted for body mass index. b

Exclude: All other outcomes; disease-specific functionality, disability, or quality of life; crude / unadjusted associations; studies where the focus is symptoms, biomarkers, clinical variables collected after disease onset.

Any length of follow-up; at least 28 days for mortality Setting

Organization for Economic Cooperation and Development countries: https://www.oecd.org/about/document/list-oecd-member-countries.htm Systematic reviews could include studies from any country.

English or French COVID-19=novel coronavirus 2019; ICU=intensive care unit; NACI=National Advisory Committee on Immunization . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 26, 2021. a The main scope differences versus the original review were: addition of a sample size requirement; inclusion of Canadian reports of any design; addition of children as an important population; inclusion of Canadian reports only for social factors; requirement of adjustment for more than age and sex for some risk factors; addition of organ injury and long-term outcomes of relevance to NACI. b Decisions for adjustment by body mass index were informed by the findings of our previous review and expert input from the Public Health Agency of Canada. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 26, 2021. COVID-19=novel coronavirus disease 2019; ICU=intensive care unit; RT-PCR=reverse transcription polymerase chain reaction a Categories do not all add to 100%, as it is possible for studies to report on more than one category (e.g., used more than one COVID-19 ascertainment method, analyzed more than one population). b Included for ß-thalassemia as no primary studies meeting the selection criteria were located. c Includes Belgium (n=1), Denmark (n=2), France (n=2), Germany (n=2), multi-country (n=3), Turkey (n=2), UK and Italy (n=1). d 14 studies did not report on patient mean or median age, one study in children did not report on patient sex/gender. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 26, 2021. ICU=intensive care unit; vs.=versus a Magnitude of associations are shown as large (OR or RR ≥2.00, or ≤0.5 for reduction) or very large (OR or RR ≥4.00). b Confidence in the magnitude of the associations was determined by considering primarily consistency in findings across studies, directness of the setting and risk factors (e.g., type of healthcare system, uncertainty about risk factor clearly matching review criteria), precision (e.g., confidence intervals indicating possibility of little to no association), and potential risk of bias. Low confidence indicates that there may be an association and moderate means that the evidence indicates that there probably is an association of the magnitude stated. c The denominator for these risk factors is the general population. These were included when findings for the risk factor-outcome comparison were not available from studies of populations with COVID-19. d These conditions were grouped within a single study; evidence for the individual conditions is either unavailable or of lower certainty. e There was evidence of a large to very large increase in mortality with grades B and C chemotherapy from one large study. However, the stages of chemotherapy were not defined, and could not be ascertained from the study's authors. In the absence of adequate information, we have grouped all stages of chemotherapy (A, B, and C) together for analysis. f Defined by hospital discharge diagnosis, in combination with drug use (filled a prescription) for the condition in the past 6 months. g General population sample that may include community and non-community dwelling people. Measured on scales that include items such as weight loss, exhaustion, physical activity, walking speed, grip strength, overall health, disability, presence of disease, dementia, falls, mental wellbeing. h Includes chromosomal abnormality, chronic kidney disease, chronic pulmonary disease, congenital heart disease, malignancy, neurological disorders, 'other', among children aged 18 years and younger.

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The copyright holder for this preprint this version posted April 26, 2021. ; https://doi.org/10.1101/2021.04.23.21256014 doi: medRxiv preprint TABLE 4. Risk factors identified in Canadian reports and potential associations with severe outcomes of COVID-19

Risk factor Reports (participants)

Living in long-term care 6 (≈2 million) Probably associated with a large increase in mortality; the association may be very large for those in their 60s and 70s. Being part of a visible minority population a 1 (8,796) May be associated with increased mortality; magnitude uncertain and findings rely on ecological data and did not account for important covariates. Living on a First Nations reserve 1 (9,715) Rates of hospitalization and mortality appear lower compared to living off-reserve. The evidence does not account for potentially important covariates such as age. Being a healthcare worker 2 (23, 101) Among those aged 30-70 years, may be associated with a large reduction in hospitalization, ICU admission, and mortality. Among healthcare workers, males appear to have higher rates of hospitalization, ICU admission, and mortality than females. Analyses did not account for important covariates. Homelessness 2 (18, 224) Very uncertain about associations with mortality. Being a homeless shelter worker 1 (1, 734) Very uncertain about associations with mortality.

Age 60-69 vs. <60 years 5 (235,481) May be associated with a large increase in hospitalization, ICU admission, and mortality. For mortality there may also be a large association when compared to 50-59 years. The magnitude of association appears to account for pre-existing medical conditions and seems similar between sexes, though absolute rates are high among men in all age groups, particularly among those not residing in longterm care or delivering healthcare. Findings for hospitalization and ICU admission may be most applicable to those living outside of long-term care as there has been limited transfer to hospital and ICU from this setting. Male vs. female 2 (11,259) Rates of hospitalization and ICU admission appear to be lower among females >30 years; after excluding health care workers, long-term care residents, and school/daycare workers and attendees, the reduction in hospitalization and ICU admission was only observed in those >50 years. Case fatality appears to be lower among females than males in the same age group. Pre-existing conditions One vs. no comorbidities 2 (15, 875) In all age groups, may have little-to-no association with mortality. Two or more vs. <2 comorbidities 1 (6, 350) Among people aged 60-79 years, may be associated with a large increase in mortality. Study data were not adjusted for important covariates like residing in long-term care. Findings for people <60 years were limited by small sample size. Compromised immunity 1 (1,734) May be associated to some extent with an increase in mortality; the magnitude of association is uncertain due to a wide confidence interval. This association was adjusted for age, long-term care residency, smoking, renal disease, diabetes, and chronic obstructive pulmonary disease.

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Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease

SARS-CoV-2 positive hospitalized cancer patients during the Italian outbreak: the cohort study in Reggio Emilia

Age-specific SARS-CoV-2 infection fatality ratio and associated risk factors

Comorbidities, cardiovascular therapies, and COVID-19 mortality: a nationwide, Italian observational study (ItaliCO)

Chronic kidney disease and acute kidney injury in the COVID-19 Spanish outbreak

National disparities in COVID-19 outcomes between Black and White Americans

Determinants of survival after severe acute respiratory syndrome coronavirus 2 infection in Mexican outpatients and hospitalised patients

Hospitalization and mortality among black patients and white patients with Covid-19

Male sex, severe obesity, older age, and chronic kidney disease are associated with COVID-19 severity and mortality

Characteristics and predictors of hospitalization and death in the first 11 122 cases with a positive RT-PCR test for SARS-CoV-2 in Denmark: a nationwide cohort

Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study

Heart failure in COVID-19 patients: prevalence, incidence and prognostic implications

COVID-19 mortality among pregnant women in Mexico: A retrospective cohort study

Association of Hypertension with all-cause mortality among hospitalized patients with COVID-19

Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area

Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study

Poor outcome and prolonged persistence of SARS-CoV-2 RNA in COVID-19 patients with haematological malignancies; King's College Hospital experience

Obesity and mortality among patients diagnosed with COVID-19: results from an integrated health care organization

Outcomes in Hispanics With COVID-19 are similar to those of Caucasian patients in suburban New York

Risk factors and outcomes of COVID-19 in New York City; a retrospective cohort study

Outcomes of patients with hypothyroidism and COVID-19: a retrospective cohort study

Hospitalised COVID-19 patients of the Mount Sinai Health System: a retrospective observational study using the electronic medical records

Association of race with mortality among patients hospitalized with Coronavirus Disease 2019 (COVID-19) at 92 US hospitals

β-Thalassemia Major and boronavirus-19, mortality and morbidity: a systematic review study

Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status -United States

Association of obesity and its genetic predisposition with the risk of severe COVID-19: analysis of population-based cohort data

Risk factors associated with mortality among residents with Coronavirus Disease 2019 (COVID-19) in long-term care facilities in Ontario, Canada

Derivation and validation of clinical prediction rules for COVID-19 mortality in Ontario

Confirmed cases of COVID-19. Ottawa ON: Indigenous Services Canada

COVID-19 in long-term care homes in Ontario and British Columbia

Incidence, clinical features, and outcomes of COVID-19 in Canada: impact of sex and age

COVID-19 death comorbidities in Canada

Statistics Canada

Descriptive epidemiology of deceased cases of COVID-19 reported during the initial wave of the epidemic in Canada

COVID-19 mortality rates in Canada's ethno-cultural neighbourhoods. Ottawa, Canada: Statistics Canada

Heterogeneity in testing, diagnosis and outcome in SARS-CoV-2 infection across outbreak settings in the Greater Toronto Area, Canada: an observational study

Informing COVID-19 vaccination priorities based on the prevalence of risk factors among adults in Canada

COVID-19: risk factors for severe disease and death

Prognosis of patients with sickle cell disease and COVID-19: a French experience

Preliminary data on COVID-19 in patients with hemoglobinopathies: A multicentre ICET-A study

Depletion of circulating IgM memory B cells predicts unfavourable outcome in COVID-19

The global impact of SARS-CoV-2 in 181 people with cystic fibrosis

Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults

Prediction models for diagnosis and prognosis of covid-19: systematic review and critical appraisal

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