The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) put an unprecedented burden on the global healthcare system, with more than 425 million infections and 5.8 million deaths to date (March 2022). Regarding disease severity, a gender difference has been observed worldwide, with women developing less severe infections than men.

Why are men more susceptible to severe COVID-19 than women?

There are many genetic, immunological, and lifestyle or behavioral factors that might increase the risk of disease severity in men.

Genetic susceptibility   

Infection with SARS-CoV-2 is initiated by the binding of the viral spike protein to host cell receptor angiotensin-converting enzyme 2 (ACE2) present on respiratory epithelial cells. This is followed by the fusion of the viral envelope with the host cell membrane and the transportation of viral RNA into the host cell.

Immunological susceptibility

Women in general exhibit a higher immune response to viral or bacterial infection than men. This could be because women have two X chromosomes instead of the one observed in men.

Lifestyle factors

Besides lifestyle and behavioral factors, certain occupational risk factors may also put men at higher risk for COVID-19. In low-skilled occupations like transportation, food processing, delivery, construction, and manufacturing, the number of male workers is significantly higher than female workers. Studies have shown that workers in these occupations are at higher risk of severe COVID-19 and mortality.