Sex Differences and COVID-19

Biological sex and psychosocial gender both play a role in many disease outcomes, and the novel coronavirus disease (COVID-19) is no different. Clinical observations in COVID-19 patient data delineate clear disparities between males and females, indicating males are at a higher risk for poorer disease outcomes. Although we are yet to understand the sex and gender-based disparities specific to COVID-19, there is evidence for sex-based differences in the endocrine, immune and renin–angiotensin system, all systems implicated in COVID-19 outcomes. Such disparities are largely thought to be driven by sex chromosomes and modulating sex hormones, which are known to vary between sex, and across the reproductive lifespan. Understanding and exploiting these driving factors are critical to understanding the pathobiology of SARS-CoV-2 virus and may lead to the development of novel therapies and increase the efficacy of preventative vaccine strategies currently under development. This chapter focuses on the endocrine, immune and renin–angiotensin system and genetic sex-based differences that could account for the meaningful differences observed in the outcomes of the SARS-CoV-2 infection.