Sex and gender differences in COVID-19: a narrative review

The coronavirus disease 19 (COVID-19) pandemic is a major challenge for all healthcare systems, as well as for social stability and the economy. The clinical spectrum of COVID-19 is: asymptomatic; mild to moderate; severe; and critical disease, leading to different fatality rates. Although countless studies have been published to better understand the pathophysiology of this infectious disease, the mechanisms of action of the virus, and the immunological responses, further research is needed to unravel the precise host factors determining COVID-19 susceptibility and severity. A considerable interest from the media and the general public has focused on the disproportionately high COVID-19-related mortality in men. This sex discrepancy may be attributed to biological, genetic and lifestyle differences between males and females, since sex is one of the variables affecting innate and adaptive immune responses, resulting in sex-specific outcomes in patients with infectious and autoimmune disorders. Therefore, in this paper we will review the available data on sex- and gender-related differences in COVID-19 susceptibility and severity.