New research suggests that levels of the sex hormones estrogen and testosterone could contribute to infection risk and severity of COVID-19. The study is published in the American Journal of Physiology-Lung Cellular and Molecular Physiology. It was chosen as an APSselect article for December.

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SARS-CoV-2, the virus that causes COVID-19, enters the body by adhering to angiotensin converting enzyme-2 (ACE2). ACE2 is present in many organs, including the lungs. Higher ACE2 levels in the body—and how well the enzyme functions—can play a role in the progression and severity of COVID-19. Previous research has also found that men fare worse than women in both severity of and death from COVID-19. It’s not clear whether these sex differences are due to distinct physiological characteristics or the influence of estrogen and testosterone.

Researchers of a new study analyzed lung tissue and airway smooth muscle cells from men and women. They first confirmed that both types of samples expressed ACE2. Then they treated the airway cells from both sexes with estrogen and testosterone. “Female patients show downregulated baseline ACE2 expression compared with males, which may reflect elevated circulating [estrogen] concentrations in females,” the authors wrote. “Perhaps more interestingly, [testosterone] significantly upregulated ACE2 expression in human [airway smooth muscle] cells,” they added. Future studies that explore whether age and metabolism of sex hormones also play a role in ACE2 expression may be helpful, the researchers suggested.