Why do men have worse COVID-19-related outcomes? A systematic review and meta-analysis with sex adjusted for age

We aimed to study the mechanism behind worse coronavirus disease-19 (COVID-19) outcomes in men and whether the differences between sexes regarding mortality as well as disease severity are influenced by sex hormones. To do so, we used age as a covariate in the meta-regression and subgroup analyses. This was a systematic search and meta-analysis of observational cohorts reporting COVID-19 outcomes. The PubMed (Medline) and Cochrane Library databases were searched. The primary outcome was COVID-19-associated mortality and the secondary outcome was COVID-19 severity. The study was registered at PROSPERO: 42020182924. For mortality, men had a relative risk of 1.36 (95%CI: 1.17 to 1.59; I-2 63%, P for heterogeneity <0.01) compared to women. Age was not a significant covariate in meta-analysis heterogeneity (P=0.393) or subgroup analysis. For disease severity, being male was associated with a relative risk of 1.29 (95%CI: 1.19 to 1.40; I-2 48%, P for heterogeneity <0.01) compared to the relative risk of women. Again, age did not influence the outcomes of the metaregression (P=0.914) or subgroup analysis. Men had a higher risk of COVID-19 mortality and severity regardless of age, decreasing the odds of hormonal influences in the described outcomes.

Automated summary

This study aimed to investigate the mechanism behind worse COVID-19 outcomes in men and whether the differences in mortality and severity between sexes are influenced by sex hormones. The findings showed that men had a higher risk of COVID-19 mortality and severity compared to women, regardless of age, suggesting a limited role of sex hormones in these outcomes.