It's X-Related: Biological Bases of Increased COVID-19 Morbidity and Mortality in Men

The document from September 2020 examined why men have higher morbidity and mortality rates from COVID-19 than women. It proposed that the X chromosome, with its immune-related genes, gives women an immunological edge due to their two copies, while men only have one. Estrogen was suggested to offer protection against severe SARS-CoV infections in females, whereas androgens might dampen the immune response in males, leading to poorer outcomes. The interaction between the androgen receptor on the X chromosome and the TMPRSS2 gene, crucial for the virus's entry into cells, was identified as a significant factor in the sex differences in disease severity. Additionally, the lower expression of the androgen receptor in prepubertal children was associated with a decreased risk of SARS-CoV-2 infection. The reasons for worse outcomes in males were considered to be complex, involving a combination of genetic, hormonal, and sex-specific vulnerabilities.