Sex‐ and Age‐Specific Differences in <scp>COVID</scp> ‐19 Testing, Cases, and Outcomes: A Population‐Wide Study in Ontario, Canada

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in late 2019 and spread globally, resulting in the COVID-19 pandemic. During the two previous coronavirus epidemics, severe acute respiratory syndrome and Middle East respiratory syndrome, male sex was associated with worse clinical outcomes.1 Emerging COVID-19 incidence and outcome data indicate that men, especially older men, may also be more affected.2-6 It is unclear whether these findings may be skewed because of unreported sex-based differences in SARS-CoV-2 testing and the age distributions of study populations.7, 8 This population-wide cohort study included all residents of Ontario, Canada, who received a nasopharyngeal swab for SARS-CoV-2 between January 23, 2020 (date swab was performed for first reported case of COVID-19 in Canada) and May 26, 2020. We excluded individuals with unknown sex. Ontario is Canada's most populous province and home to nearly 15 million residents who receive universal access to medically necessary services including laboratory testing for SARS-CoV-2 under a publicly funded provincial health insurance program. We obtained data for this study from the Ontario Ministry of Health as part of the province's emergency “modeling table,” including deidentified line level data on all SARS-CoV-2 testing via the Ontario Laboratories Information System and from the integrated Public Health Information System for all reported COVID-19 cases and related clinical outcomes. We reported sex- and age-disaggregated data on SARS-CoV-2 testing, COVID-19 cases and related rates of hospitalization, intensive care unit (ICU) admission, and death. We used census data from Statistics Canada to compare sex-based testing by age with the sex and age distribution of the Ontario population. Among laboratory-confirmed COVID-19 cases, we used logistic regression to estimate sex-based odds ratios for hospitalization, ICU admission, and death, adjusting for 10-year age intervals, with the level of statistical significance set at α = .05. All analyses were performed using SAS statistical software, v.9.4 (SAS Institute Inc). The study was approved by the research ethics board of the University of Toronto. A total of 233,566 unique Ontario residents (150,195 females [64.3%] vs 83,371 males [35.7%]) received testing for SARS-CoV-2 between January 23, 2020, and May 26, 2020 (Table 1). With the exception of two age groups (ages 0–9 years and 70–79 years), males received less testing for SARS-CoV-2 than would be expected for their age-based representation in the Ontario population (Table 1). Compared with females, males had a higher rate of laboratory-confirmed COVID-19 infection (11,285 males [13.5%] vs 14,678 females [9.8%]), a finding consistent across all age groups (Table 1). Among all individuals with COVID-19 infection, males had higher rates of hospitalization (1,764 males [15.6%] vs 1,520 females [10.4%]), ICU admission (458 males [4.1%] vs 256 females [1.7%]), and death (980 males [8.7%] vs 1,116 females [7.6%]) (Table 2). In age-adjusted analyses, male sex was associated with a higher odds of hospitalization (adjusted odds ratio [aOR] = 1.76; 95% confidence interval [CI] = 1.63–1.90; P < .001), ICU admission (aOR = 2.24; 95% CI = 1.91–2.62; P < .001), and death (aOR = 1.70; 95% CI = 1.54–1.88; P < .001) (Table 2). We found that although more females than males were tested for SARS-CoV-2, males had a higher rate of laboratory-confirmed COVID-19 infection, hospitalization, ICU admission, and death. These findings were consistent even with age adjustment, suggesting that the observed differences in outcomes between females and males were not explained by age or systematic differences in testing by sex. Instead, they may be due to sex-based immunological or other gendered differences, such as higher rates of smoking leading to cardiovascular disease.4-6, 9 The study is limited to a single region and could not control for underlying differences in sociodemographic characteristics and comorbidities between females and males. A recent multinational analysis reported that compared with women, men had higher COVID-19 case fatality rates that were not completely explained by their higher prevalence of comorbidities.10 We also could not identify healthcare workers, most of whom are women, which could explain some of the sex-based differences in SARS-CoV-2 testing. With most regional health systems failing to report fully sex-disaggregated data on COVID-19, our study highlights how sex-specific reporting can guide a more gender-responsive approach to the global pandemic.1, 2, 9 In particular, our findings can inform pathways for COVID-19 care including targeting older men as a particularly at-risk group that may benefit from intensified prevention and earlier intervention.1, 5, 8 This research was not funded. Nathan Stall is supported by the Department of Medicine's Eliot Phillipson Clinician-Scientist Training Program and the Clinician Investigator Program at the University of Toronto, and the Vanier Canada Graduate Scholarship. David Fisman is supported by a grant from the Canadian Institutes of Health Research (2019 COVID-19 rapid research funding OV4-170360). Paula Rochon holds the RTOERO Chair in Geriatric Medicine at the University of Toronto. All the authors have declared no conflicts of interest for this article. Nathan Stall, Lauren Lapointe-Shaw, and Paula Rochon contributed to the conception and design of the work. All of the authors acquired, analyzed, and interpreted the data. Wei Wu performed the statistical analysis. Nathan Stall drafted the manuscript. All of the authors critically revised the manuscript for important intellectual content and agreed to be accountable for all aspects of the work. None.

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