Study explores biological sex as a determinant for COVID-19

A physician fills out medical charts for a COVID-19 research study

SARS-COV-2, the pathogen that causes the novel coronavirus, has affected millions of people in hundreds of countries since December 2019. Patient registries from China and Italy show men have had higher infection, hospitalization, and death rates compared to women. Researchers at Wake Forest University explore these trends in a review, “Is Sex a Determinant of COVID-19 Infection? Truth or Myth?,” funded by the National Heart, Lung, and Blood Institute and published in Current Hypertension Reports.

The authors note estrogen, a reproductive female sex hormone, provides a protective effect against cardiovascular disease. On average, between 15-30% of COVID-19 patients have high blood pressure and 2.5-15% have coronary artery disease.

“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,” Leanne Groban, M.D., lead study author, said in a release issued by Wake Forest Baptist Health.

The researchers explain angiotensin-converting enzyme 2 (ACE2), the pathway for SARS-COV-2 to enter cells and cause infection, is found on endothelial cells, which line blood vessels, and epithelial cells, which provide a barrier between skin and other organs in the body. The lung, heart, kidney, testis, and gastrointestinal tract are common sites for SARS-COV-2 infection, or COVID-19.

The researchers note the role estrogen receptors, X chromosomes, and environmental factors have in influencing ACE2 expression may account for differences in how men and women respond to the virus. Tracking sex-based differences in global data banks is one way to collect ongoing data about biological sex as a determinant of COVID-19.

Collecting additional information about circulating hormone levels, which vary with age and menopause, or as a result of taking hormone therapies, may also help clinicians recommend or create new therapies. Two clinical trials in the U.S. are testing the role estrogen may have in helping hospitalized men and older women recover from COVID-19.

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