An Unsolved Mystery: Why Do More Men Die of Covid-19?

Azita Ghahramani worried she wouldn’t survive Covid-19 because of her health conditions, including high blood pressure. So she and her husband, Scott Downing, and their son became hypervigilant. They moved to a remote part of Maine and avoided most social interactions. Even so, all three got Covid-19 in March 2021, possibly from exposure during a family funeral. But it wasn’t Ms. Ghahramani who nearly died of the disease; it was her husband.

Despite being in his 50s and an avid tennis player, eating healthfully and having no medical conditions, Mr. Downing ended up in the intensive care unit. Nearly eight months later, he remains out of work on sick leave and only recently started weaning off supplemental oxygen at night.

Ms. Ghahramani is an acquaintance of my family, and her husband’s case is a good example of a persistent pandemic issue. Men are much more likely than women to die of Covid-19 and are more likely to be intubated and have long hospitalizations. This disparity in Covid-related deaths has existed since early in the pandemic, before there were any vaccines. Men are also more likely to develop certain rare complications from some Covid-19 vaccines and to experience a faster decline in measures of immunity once vaccinated. The reasons remain unclear.

Historically, women have been largely excluded from medical studies, and health issues that predominantly affect women have been underresearched. This is both morally wrong and medically foolish because it limits physicians’ ability to deliver optimal care. Rather than ignore sex differences in Covid-19 outcomes, scientists should pay attention to them to better understand the disease and how to treat it.

Data from the Centers for Disease Control and Prevention shows that in the United States, women account for 45.6 percent of Covid-19 deaths so far and men account for 54.4 percent. (Men make up slightly less than half the U.S. population.) Among Americans ages 65 to 84 — the group at highest risk for severe Covid-19 — the gap is even larger: 57.9 percent of deaths have occurred among men and 42.1 percent among women. According to the Brookings Institution, at least 65,000 more men than women have died of Covid-19 in the United States. Globally, the death rate has been about 50 percent higher for men.

A July 2021 study found that compared to women, men with Covid-19 had an almost 50 percent higher rate of respiratory intubation and a 22 percent longer hospital stay.

Certain complications from Covid-19 vaccines, though rare, seem to happen more often among men than women. A recent study from Israel on the Pfizer-BioNTech vaccine showed that the incidence of myocarditis — inflammation of the heart muscle — was nearly 18 times as high among men as among women over age 16.

There is also evidence that immunity from the Pfizer vaccine wanes more rapidly among men. Another recent study from Israel found that six months after the second dose of the vaccine, levels of antibodies were “substantially lower among men than among women.” Among men age 65 and older, certain antibody levels after vaccination were 46 percent lower than among vaccinated women of the same age.

What might account for these differences?

Some think the higher Covid-19 death rates among men are due to lower vaccination rates. Just over 50 percent of American men are fully vaccinated, compared to 55 percent of women. However, vaccination rates alone cannot account for all the worse Covid-19 outcomes among men, since the disparities in deaths and other complications predate the availability of the vaccines.

Some researchers suggest that the higher death rate among men is spurious, an unrelated curiosity. Others contend that factors like adherence to mask wearing or underlying health conditions most likely explain the differences. Early on, for example, it was suggested that this sex difference might be traced to higher rates of smoking among men in China, where the disparity was first observed.

Work and other social factors like masking might have a role, though women make up a very high proportion of essential workers and are more likely to hold jobs as home health aides and nursing home caregivers, which can expose them to Covid-19.

There are also biological explanations for differences that must be elucidated or at least deserve further study.

Yale University researchers noted that there are well-established differences in immune responses to infections between men and women. Diseases like tuberculosis are more common among men, for example, and men tend to have higher viral loads of hepatitis C virus and H.I.V. The same researchers found differences in men’s and women’s immune responses to Covid-19. Men with Covid-19 had higher blood levels of inflammatory proteins that regulate immune responses, for example. This could lead to an overexuberant immune response to the coronavirus.

Other researchers argue that hormonal factors might be at play. Testosterone may tamp down men’s immune response, while estrogen may play a role in women’s tendency to have more immune B cells, which produce antibodies. Estrogen may inhibit the kind of immune cells that are thought to play a role in myocarditis.

Still, the reasons men seem to fare worse remain mostly a mystery. Much more research is needed to understand it, and there are most likely several factors at play.

The medical community needs to be more open to exploring sex differences in disease. One way to respond to the Covid-19 death-rate disparity now is to target men for vaccines and boosters.

The National Institutes of Health recently awarded $470 million to over 30 institutions to support research into long Covid, another pandemic phenomenon. Much could be gained from an equivalent research effort 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.

Ezekiel J. Emanuel (@ZekeEmanuel) is the vice provost of global initiatives and a professor of medical ethics and health policy at the University of Pennsylvania.

The Times is committed to publishing a diversity of letters to the editor. We’d like to hear what you think about this or any of our articles. Here are some tips. And here’s our email: [email protected].

Follow The New York Times Opinion section on Facebook, Twitter (@NYTopinion) and Instagram.