The Physiological Mechanisms of the Sex-Based Difference in Outcomes of COVID19 Infection

The scale of the SARS-CoV-2 pandemic has thrust a spotlight on the sex-based differences in response to viral diseases; morbidity and mortality are greater in men than women. We outline the mechanisms by which being female offers a degree of protection from COVID19, that persists even when confounders such as comorbidities are considered. The physiological and immunological mechanisms are fascinating and range from incomplete X chromosome inactivation of immune genes, a crucial role for angiotensin converting enzyme 2 (ACE2), and regulation of both immune activity and ACE2 by sex steroids. From this flows understanding of why lung and other organs are more susceptible to COVID19 damage in men, and how their distinct immunological landscapes need to be acknowledged to guide prognosis and treatment. Pregnancy, menopause, and hormone replacement therapy bring changed hormonal environments and the need for better stratification in COVID19 studies. We end by noting clinical trials based on increasing estrogens or progesterone or anti-testosterone drugs; excellent examples of translational physiology.

Automated summary

The SARS-CoV-2 pandemic has highlighted sex-based differences in response to viral diseases, with men showing higher morbidity and mortality than women. Female protection against COVID19 is linked to fascinating physiological and immunological mechanisms, while men's distinct immunological landscapes make them more susceptible to COVID19 damage, requiring tailored research and treatment approaches. Clinical trials exploring the effects of increasing estrogens, progesterone, or anti-testosterone drugs serve as excellent examples of translational physiology in this context.