Q. Why have more men than women died from or been severely affected by the coronavirus that causes Covid-19?
Researchers have found that the immune systems of men and women differ in important ways. For example, women have higher numbers of specific immune cells (including a type known as “helper” cells) and a more favorable ratio of certain immune cell types than same-aged men. When challenged with a specific pathogen, women on average generate higher levels of antibodies (specific immune proteins to battle the pathogen) than men do. Women also have historically been shown to generate a stronger immune response to numerous vaccines, including those given to prevent smallpox, influenza, and herpes zoster.
It’s not completely clear what accounts for women’s apparent immune edge. One popular hypothesis is that the female hormones estrogen and progesterone exert a positive effect on the immune system. Lab studies have shown, for example, that exposing key virus-fighting cells (called natural killer cells) to estrogen increases their activity; estrogen also appears to help regulate the production of cytokines, inflammatory proteins that the immune system uses to battle infection.
In contrast, some research suggests that male hormones (androgens, such as testosterone) may negatively affect immunity. For instance, men who are naturally deficient in androgens have been found to mount better antibody responses to infection and to have more favorable immune cell ratios (as mentioned above), compared to men who have normal androgen levels.
An Italian study published in the Annals of Oncology in May 2020 lends some support to the hormone hypothesis when it comes to Covid. The investigators looked at data from men with prostate cancer in the Veneto region of Italy, which was heavily affected by the coronavirus outbreak. Men who were receiving androgen deprivation therapy—a treatment that blocks androgens such as testosterone that can fuel tumor progression—had less than one-quarter the likelihood of testing positive for Covid than men not receiving the therapy. This suggests that their lower androgen levels may have helped protect them against infection.
