COVID-19: What’s Sex Got to Do with It?

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The ongoing COVID-19 pandemic continues to challenge the scientific community. Scientists across the globe are still trying to figure out the risk factors for severe COVID-19. Being male seems to be a higher risk, and many researchers are looking into why males experience COVID-19 symptoms more severely than females.

My lab studied the role of sex steroids, estrogen and testosterone in the COVID-19 pathophysiology. We found the sex-skewed occurrence of COVID-19—which showed that more men were becoming sick than women—to be eye-opening. We used airway smooth muscle cells to investigate the crucial role that the ACE2 receptor plays on sex hormones (also called sex steroids) in the body in the context of COVID-19. The SARS-CoV-2 virus binds to ACE2 receptors to get into the human body—it’s the virus’ “entry ticket.” Learning more about this receptor is hot topic for researchers who are trying to find answers to the COVID-19 question. In 2020, my research team looked to unravel the expression of this crucial receptor, ACE2, in the airway smooth muscle cells. Our research brought up some questions about ACE2 and biological sex.

Our findings suggested that ACE2 does not present equally across the sexes, which potentially explains why more men were becoming infected with the SARS-CoV-2 virus than women. We found significantly lower expression of the ACE2 receptor in women of all ages, ranging from the child-bearing years to menopause, as compared to men.

A major difference between biological males and females is the levels of circulating sex steroids in the body. While males secrete high levels of testosterone, they do have a small amount of estrogen in their bloodstream. However, females have much more estrogen, which helps to regulate the menstrual cycle and other reproductive functions. Our research found that testosterone contributes to higher ACE2 expression in airway cells, while estrogen leads to less expression. This in part explains why men have a higher risk of developing more severe COVID-19 symptoms than women.

As the pandemic continues, so does research about the SARS-CoV-2 virus and the disease it causes, COVID-19. Scientists don’t have all the answers yet, and we can’t control our biological sex. However, as researchers, we can improve our practice and scientific approach toward research that is inclusive of both sexes. Over the next few years, I hope to see more progress in sex and gender-specific studies and therapeutics to help treat and potentially prevent lung diseases such as COVID-19.

Niyati Borkar is a PhD student in pharmaceutical sciences at North Dakota State University. Her research focuses on understanding the role of sex steroids in the sex-skewed occurrence of asthma. Borkar is a Graduate Student Ambassador for the American Physiological Society and is an avid scientific communicator. 

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