Revisiting biological sex as a risk factor for COVID-19: a fact or mirage of numbers?

Abstract

AbstractBiological sex is considered a risk factor for COVID-19. The prevailing view supposes males are about two-fold more impacted than females based on early-stage studies. The observed higher male deaths in COVID-19 are purportedly a result of biological differences that make males more vulnerable to adverse outcomes in infectious diseases. Research and policy paradigms seem to follow a similar line of thought to mitigate COVID-19 impact on populations. The analysis of sex-disaggregated data could help us evaluate the veracity of assertions for a preferred evidence-guided response. The analysis of the sex-disaggregated data available for the top 70 countries contributing about 80% of total deaths (as of 15 September 2021; on average two waves of infections experienced) indicates average Case Sex (Male: Female) ratio (CSR) of 1.09±0.35 (marginally more male cases) and Death Sex ratio (DSR) of 1.48± 0.47. Consideration of only laboratory-confirmed cases indicates the mortality sex ratio (MSR) in COVID-19 (MSR-COVID) to be 1.37±0.30. The prevailing MSR for the same countries was 1.758±0.409. The relative change in the mortality rate for males as compared to females in COVID-19 (ratio: MSR-COVID/prevailing MSR-PP) was 0.818±0.261 much lower than anticipated (2 or higher). Overall, over three-fold more countries (51/70) experienced a higher rate of female mortality than male mortality (15/70). Together, it suggests a more disproportionately severe impact of COVID-19 on females than on males, contrary to the prevailing view. Identification and analysis of country-specific factors contributing to differential impact on sexes, whether biological or environmental, seem warranted.