Sexual dimorphism in COVID-19: potential clinical and public health implications

Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.

Automated summary

Current evidence shows that COVID-19 severity and mortality are higher in men compared to women, while women may be at a higher risk of reinfection and long-term COVID-19 development. Differences between sexes have also been observed in other infectious diseases and vaccine responses. This could be explained by sex-specific expression patterns of proteins involved in virus binding and entry, as well as divergent reactions of the immune and endocrine systems to acute stress. Understanding the role of sex hormones, comorbidities, and sex chromosome complement in COVID-19 could have implications for disease treatment, public health measures, and follow-up of patients predisposed to long COVID. Considering sex differences in future pandemic surveillance and COVID-19 patient treatment may lead to better disease stratification and improved outcomes.