Biological sex differences play critical roles in health, a circumstance observed in the higher rates of severe outcomes or death among men diagnosed with COVID-19, despite nearly equal infection rates among both sexes. Authors of a recent review suggest that these anomalies may be due to sex-based differences in the number of two proteins: the angiotensin-converting enzyme 2 receptor and the toll-like receptor 7.

The angiotensin-converting enzyme 2 (ACE2) receptor is widely distributed among the body’s tissues. It plays key roles in the maintenance of blood pressure. SARS-CoV-2, the virus that causes COVID-19, exploits ACE2 to gain entry into cells by binding to a cell’s ACE2 receptor and injecting its genetic material into the cytosol, where it can replicate. Normal ACE2 function is markedly impaired in COVID-19 illness. The authors of the review report that women express twice the number of ACE2 receptors as men, providing a sort of “backup” population of receptors to carry out their normal function.

Toll-like receptor 7 (TLR-7) is an element of the body’s immune response. It facilitates pathogen recognition and activates innate immune function. Women express twice the number of TLR-7s than men. The authors report that this translates to a more robust immune response among women than among men.

The authors also pointed out that hormonal differences (such as higher estrogen levels in women) and sociocultural factors influence the differential COVID-19 risk profiles among men and women. They posited that repurposing drugs that affect ACE2, such as ACE2 inhibitors and ACE2 receptor blockers may be useful in treating COVID-19.

• Link to review abstract.