Men more likely to experience severe cases of COVID-19: study

A recent study by a team of researchers from the University of Toronto’s Pandemic and Emerging Infections Consortium (EPIC) has shed light on the biological reasons underlying gender differences in COVID-19 outcomes.

This discovery offers a promising new strategy to prevent the disease and could have a significant impact in the fight against the pandemic.

The research, which was published in the journal iScience, represents an important advance in the understanding of why men are more likely to suffer severe or fatal outcomes from COVID-19 compared to women, despite having similar infection rates.

Since the first days of the pandemic, doctors found that men faced a higher risk of hospitalization, ICU admission and death due to COVID-19, regardless of age and geographic location. This gender disparity in disease severity raised crucial questions that motivated the research.

The study’s lead author, Haibo Zhang, a scientist at the Keenan Research Center for Biomedical Sciences at St. Michael’s Hospital, Unity Health Toronto, and professor of anesthesiology, pain medicine and physiology at U of T’s Temerty School of Medicine, He explained the motivation behind his work.

“The severity and mortality of COVID-19 are much higher in men than women, but the reasons for this are still not well understood,” he said.

Blood pressure and inflammation

The research was conducted in collaboration with five hospital research partners under EPIC, a U of T strategic initiative addressing high-risk, high-burden infectious diseases.

The study focused on the ACE2 protein, which plays a crucial role in controlling blood pressure and inflammation, as well as protecting organs from damage caused by excessive inflammation.

The particularity of ACE2 is that the gene that codes for it is located on the X chromosome, which means that women have two copies of this gene, while men have only one.. Under healthy conditions, this difference does not appear to have a significant impact on ACE2 levels in healthy men and women.

However, after a SARS-CoV-2 infection, researchers observed a dramatic decrease in ACE2 in men, while levels remained constant in women. This suggests that the extra copy of the ACE2 gene on the X chromosome in women could be helping to compensate and maintain higher levels of ACE2 protein, which could have a protective effect.

Additionally, changes in ACE2 levels were correlated with a decrease in estrogen hormone signaling in men. This observation suggests that the hormone estrogen, present in higher amounts in women, could also play a role in gender differences in COVID-19 outcomes.

To test the hypothesis that low levels of ACE2 in men contribute to more severe COVID-19 outcomes, researchers developed a therapeutic approach.

They used an inhaler to deliver lab-made ACE2 proteins directly into the lungs of male patients infected with SARS-CoV-2. The results were encouraging: Men who received this therapy had less virus in their lungs, less lung damage, and higher levels of estrogen signaling.

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