Does gender influence clinical expression and disease outcomes in COVID-19? A systematic review and meta-analysis

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) was characterized at the end of 2019, and soon spread around the world, generating a pandemic. It has been suggested that men are more severely affected by the viral disease (COVID-19) than women. Objective: The aim of this systematic literature review (SRL) and meta-analysis was to analyse the influence of gender on COVID-19 mortality, severity, and disease outcomes. A SRL was performed in PubMed and Embase, searching terms corresponding to the ‘PEO’ format: population = adult patients affected with COVID-19; exposure = gender; outcome = any available clinical outcomes by gender, including mortality and disease severity. The search covered the period from January 1 to April 30, 2020. Exclusion criteria were: case reports/series, reviews, commentaries, languages other than English. Full-text, original articles were included. Data on study type, country, and patients’ characteristics were extracted. Study quality was evaluated using the Newcastle–Ottawa scale (NOS). From a total of 950 hits generated by the database search, 85 articles fulfilling the inclusion criteria were selected. Results: A random-effects meta-analysis was performed to compare mortality, recovery rates, and disease severity in men compared with women. The male to female ratio for cases was 1:0.9. A significant association was found between male sex and mortality (OR = 1.81; 95% CI 1.25–2.62), as well as a lower chance of recovery in men (OR = 0.72; 95% CI 0.55–0.95). Male patients were more likely to present with a severe form of COVID-19 (OR = 1.46; 95% CI 1.10–1.94). Conclusions: Males are slightly more susceptible to SARS-CoV2 infection, present with a more severe disease, and have a worse prognosis. Further studies are warranted to unravel the biological mechanisms underlying these observations.