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

Abstract

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.

Gender differences in COVID-19

“…On the other hand, women appear to be at greater risk of reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, the persistence of symptoms over a long period of time after infection, a condition known as long COVID, is more common in women than in men [1] , [4] , [5] . Another interesting observation is that women are more likely to experience, or at least to report more frequently, side-effects after COVID-19 vaccination, including fever and pain at the site of injection [4] , [5] .…”

“…Also, the persistence of symptoms over a long period of time after infection, a condition known as long COVID, is more common in women than in men [1] , [4] , [5] . Another interesting observation is that women are more likely to experience, or at least to report more frequently, side-effects after COVID-19 vaccination, including fever and pain at the site of injection [4] , [5] . Moreover, it seems that the transient endothelial and inflammatory response after vaccination is larger in women, which may indicate greater protection in women [6] .…”

“…Interestingly, the substantial divergence in various characteristics and functions between males and females is reflected in sex-specific differences in disease susceptibility and outcomes. Biological sex is ultimately associated with a difference in human life span, as women have a higher life expectancy [5] .…”

“…How do the above gender differences affect the clinical course of COVID-19? Overall lower life expectancy in men has already been ruled out as a major contributor to their increased mortality due to COVID-19 [4] , [5] . However, patients with comorbidities, such as diabetes mellitus, hypertension and cardiovascular disease, have a higher risk of serious disease [7] .…”

“…However, patients with comorbidities, such as diabetes mellitus, hypertension and cardiovascular disease, have a higher risk of serious disease [7] . Indeed, men are more likely to present such comorbidities than women [1] , [4] , [5] . Moreover, there are distinct gender differences in metabolism regulation, including insulin sensitivity and lipid metabolism [8] .…”