WVU expert discusses why COVID-19 kills more men than women

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MORGANTOWN, W.Va. – While men are not more likely to contract COVID-19 than women, once infected, they are more likely to suffer from severe complications or die from it.

This is according to Jennifer Franko, a teaching assistant professor in the West Virginia University School of Medicine, who studies sex differences in immune responses. Franko said there are many factors that contribute to this disparity and one of them is simply that in general, men tend to be more susceptible to infection than women.

“While this difference may or may not be specific to coronaviruses, similar trends were seen in previous coronavirus outbreaks, including Severe Acute Respiratory Syndrome (SARS) in 2003 and Middle East Respiratory Syndrome (MERS) in 2012,” Franko said in a WVU press release. “In both of these instances, higher mortality rates were reported in males versus females. It’s the same situation that we’re seeing now with SARS-CoV-2 (COVID-19).”

Franko said a less robust immune response in males may result in slower viral clearance and poorer outcomes when dealing with COVID-19. Some of these differences between men and women, she said, could be a result of the hormonal or genetic factor.

As an example, Franko said in the release, in females, estrogen and progesterone are typically thought to stimulate the immune system and may provide a higher level of protection against infection. Whereas, in males, testosterone may suppress such a response.

Jennifer Franko

From a genetics standpoint, many immune-related genes are encoded on the X chromosome. Females have two copies of the X chromosome. Males have only one. In order to balance the dosage of X-linked genes between males and females, one female X chromosome is typically inactivated. Interestingly, we are now beginning to realize that not all of those X-chromosome-linked genes are inactive all the time. In some instances, these genes escape inactivation, resulting in a double dosage effect and higher levels of gene expression in females. If these are immune-related genes, they may correlate with stronger immune responses. This may be an additional reason why females respond to infection with more robust responses.

Jennifer Franko – WVU School of Medicine

And Another factor that could account for the disparity, Franko said, is that males may have more underlying conditions that may amplify their risk of severe complications and death. Underlying factors like hypertension or heart disease can lead to worse outcomes when COVID-19 is factored in.

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