There needs to be a broader study of how biological sex differences affect outcomes with COVID-19, researchers argue in a recent paper.
Because these findings are cutting across social and cultural boundaries, that strongly suggests the biological difference between males and females is contributing. That likely doesn’t tell the full story, however—social and lifestyle factors may certainly be influencing the trends, but we need to understand more.
A sex difference in immune responses that control and clear SARS-CoV-2 suggests there there’s a difference between sexes affecting immunity. We have data for other viruses illustrating that sex differences in immunity are caused by genetic as well as hormonal differences between women and men. For example, in females, hormones such as estrogen and progesterone may be protective against the virus, and it’s possible testosterone does the opposite for men.
Scientists are also looking into the role of the ACE-2 receptor, which is found on the cells lining the lung and airways and is used by the SARS-CoV-2 virus to enter cells. From what we know about this receptor, from other conditions such as hypertension and kidney disease, ACE-2 expression is greater in males than in females. We also know from work in the kidneys that estrogen downregulates the expression of ACE-2, which could be a plausible biological explanation for reduced severity of the virus in women.
There are also underlying conditions such as hypertension, heart disease, and diabetes, which men are statistically more likely to have and some of which can be attributed to lifestyle factors, that also amplify risks with COVID-19.