COVID: the Risk of Death is 70% Higher for Male than for Female Patients

Evidence increasingly indicates that male sex is a risk factor for more severe disease and death from COVID-19. Male bias in COVID-19 mortality is observed in nearly all countries with available sex-disaggregated data, and the risk of death in males is ∼1.7 times higher than in females. Aging is strongly associated with higher risk of death in both sexes, but at all ages above 30 years, males have a significantly higher mortality risk, rendering older males the most vulnerable group. Sex differences are intertwined with differences in gender roles socially and with behavioral factors, which also influence COVID-19 incidence and outcomes. However, there are also possible biological mechanisms of male sex bias that affect the severity of COVID-19, particularly with respect to immune responses.

Sex differences beyond sex organs are present across species and extend to physiological systems, including the immune system. Infection by different pathogens results in differential immune responses and disease outcomes by sex, and although the pattern depends on age and other host factors, male sex is more often associated with lower immune responses and higher susceptibility and/or vulnerability to infections in animals. This is generally also the case in humans: Male patients have higher viral loads for hepatitis B virus (HBV) and HIV. Conversely, females generally mount a more robust immune response to vaccines, such as influenza vaccines. However, the heightened immune responses in females can also lead to detrimental immunopathology in infections.

The physiological response to virus infection is initiated when virus replication is detected by pattern recognition receptors. This leads to two antiviral programs by the infected cells.