According to CDC data, men are more likely than women to experience worse outcomes from Covid-19, including more severe symptoms and death—but the reason why is unclear. Writing for the New York Times, Ezekiel Emanuel, the vice provost of global initiatives and a professor of medical ethics and health policy at the University of Pennsylvania, explains some potential factors behind this disparity, and why more research is needed to explore these sex differences.

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Men face worse Covid-19 outcomes than women

According to Emanuel, there are significant sex differences when it comes to Covid-19 outcomes, with men faring worse than women on several different measures.

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For example, men are more likely experience severe effects of Covid-19. A study published in PLoS One found that male Covid-19 patients had an almost 50% higher rate of respiratory intubation and a 22% longer hospital stay than female Covid-19 patients.

Men are also more likely to die from Covid-19 than women, a disparity which Emanuel writes has existed "since early in the pandemic, before there were any vaccines."

According to CDC data, women currently make up 45.6% of Covid-19 deaths in the United States, while men, who make up slightly less than half of the U.S. population, account for 54.4% of Covid deaths. This difference widens even further among Americans ages 65 to 84, who are at the highest risk of severe Covid-19, Emanuel writes. Among this group, 57.9% of Covid-19 deaths have occurred in men, compared to 42.1% in women. Overall, the Brookings Institution estimates that at least 65,000 more men in the United States have died from Covid-19 than women.

In addition, Emanuel writes that there may be differences in how men and women respond to Covid-19 vaccines. In particular, men may be more likely to develop certain rare complications after Covid-19 vaccination than women. A study from Israel examining the effects of the Pfizer-BioNTech Covid-19 vaccine that the rate of myocarditis, an inflammation of the heart muscle, was almost 18 times higher in men than women ages 16 and older.

There is also evidence suggesting that immunity from vaccination wanes more quickly in men than women. Another study from Israel found that antibody levels were "substantially lower among men than women" six months after the second dose of Pfizer-BioNTech's vaccine. Among vaccinated men age 65 and older, certain antibody levels were 46% lower than vaccinated women of the same age.

The potential reasons behind the disparity

Why men experience worse Covid-19 outcomes than women is "mostly a mystery," Emanuel writes, but researchers have posited several possible explanations.

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According to Emanuel, some researchers believe that higher Covid-19 death rates are largely due to lower vaccination rates. In the United States, just over 50% of men are fully vaccinated, but 55% of women are fully vaccinated. However, Emanuel notes that vaccination cannot account for all these Covid-19 disparities, since many of them were observed even before the vaccines were available.

Other researchers have suggested that factors such as work, mask wearing, or underlying health conditions may play a role in the differences between men and women. For example, in China, men's higher smoking rates may have caused them to experience more severe Covid-19 outcomes.

There are also potential biological explanations for the differences between men and women, Emanuel writes. In an article published in Nature, researchers from Yale University noted that there are well-established differences in men's immune responses to infections when compared with women. The same researchers found differences in men's and women's responses to Covid-19, finding that men had higher blood levels of inflammatory proteins that regulate immune responses, which could have led to "an overexuberant immune response to the coronavirus," Emanuel writes.

In addition, hormones may play a role in how men and women respond to the coronavirus. Testosterone may dampen men's immune response, leading to more severe Covid-19. Estrogen, on the other hand, may be why women have more antibody-producing B cells and may inhibit immune cells that cause myocarditis.

Although an exact cause of the disparity in Covid-19 outcomes is still unknown, Emanuel writes that "[t]he medical community needs to be more open to exploring sex differences in disease."

He adds, "One way to respond to the Covid-19 death-rate disparity now is to target men for vaccines and boosters."

Overall, Emanuel encourages more research into the higher rate of Covid-19 deaths, complications, and waning immunity among men. "Rigorously looking at the differences in Covid-19's toll and discovering the underlying causes is imperative to better understanding this disease—as well as other infectious diseases—and how to treat it," he writes. (Emanuel, New York Times, 11/2)