Sex-Bias in COVID-19: A Meta-Analysis and Review of Sex Differences in Disease and Immunity

BACKGROUND: There have been anecdotal reports of a male sex bias in COVID-19. We aimed to perform a meta-analysis of available case reports to investigate whether there was a difference in the proportion of males and females infected with COVID-19 and whether sex associated with a difference in risk of ITU admission or death. METHODS: We performed a meta-analysis of 29 reports. An internet search was performed for reports in any language that included sex as a variable when describing case numbers, ITU admissions or death between 01.01.20-30.03.20. Reports were excluded if they did not reported the sex difference in overall case numbers or where there was possible duplication. Summary level data were extracted from reports. Meta-analyses were used to assess the proportion of males and females in total numbers of confirmed cases, to estimate odds ratios (ORs) with 95% CI associated with sex for ITU admission and death based on pooled average effect measures that were weighted according to the size and precision of each report. Fixed and random effects models were estimated. FINDINGS: 29 studies were eligible with a total of 206,128 cases. The proportion of male cases with COVID-19 was 0.52 (95% CI=0.50,0.53, p=0.12 for random effects model). Male sex associated with an increased risk of ITU admission (OR=2.50, 95% CI=2.25,2.78; 7.3e-64 for random effects model; n=43,075). Male sex associated with an increased risk of mortality (OR=1.60, 95% CI=1.41, 1.82, p=7.4e-13 for random effects model; n=170,983).