Breaking it down
The study, conducted at Wake Forest School of Medicine, investigated the role that sex-specific hormones, especially estrogen, play in protecting women from more severe cases of COVID-19.
“We know that coronavirus affects the heart and we know that estrogen is protective against cardiovascular disease in women, so the most likely explanation seemed to be hormonal differences between the sexes,” lead author of the review, Leanne Groban, M.D. said.
The team reviewed previously published preclinical data on sex-specific hormone activity. What they found was that estrogen lowers the level of angiotensin-converting enzyme2 (ACE2) in the heart. ACE2 is the cellular receptor of the coronavirus that brings the virus into the cells of the heart, arteries, kidneys and intestines.
According to the study, by lowering the level of ACE2 in the heart, estrogen helps modulate the severity of COVID-19 in women. This would also explain why, statistically, women experience less severe symptoms of COVID-19 than men.
“We hope that our review regarding the role of estrogenic hormones in ACE2 expression and regulation may explain the gender differences in COVID-19 infection and outcomes, and serve as a guide for current treatment and the development of new therapies,” Groban said.
This study is not the first, however, to show the benefits estrogen has in protecting women from viruses. A 2016 study, published in The American Journal of Physiology, found that estrogen was also effective in protecting women against the flu.
According to the lead investigator of the 2016 study, Sabra Klein, Ph.D., a virus causes sickness by entering a cell and making copies of itself. When released from infected cells, the virus then spreads through the body and even to other people. More replication of the virus means a more severe case and vice versa.
What did they discover?
In this case, researchers discovered that estrogen reduced the replication of the flu virus in nasal cells from women, causing less severe cases of the flu and reducing the likelihood of transmission.
“Other studies have shown that estrogens have antiviral properties against HIV, Ebola and hepatitis viruses,” Klein said. “What makes our study unique is two-fold. First, we conducted our study using primary cells directly isolated from patients, allowing us to directly identify the sex-specific effect of estrogens. Second, this is the first study to identify the estrogen receptor responsible for the antiviral effects of estrogens, bringing us closer to understanding the mechanisms mediating this conserved antiviral effect of estrogens.”
Klein even suggested, in this case, that women on certain forms of birth control or hormone replacements may be better protected than others during flu season.
“Because estrogen levels cycle in premenopausal women, it may be difficult to see this protective effect in the general population,” she said. “But, premenopausal women on certain kinds of birth control or post-menopausal women on hormone replacement may be better protected during seasonal influenza epidemics. We see clinical potential in the finding that therapeutic estrogens that are used for treating infertility and menopause may also protect against the flu.”