Why COVID-19 Hits Men Harder Than Women

One explanation researchers have zeroed in on: Men don't produce as powerful an immune response as women. In a recent study, Iwasaki and her colleagues followed about 40 COVID-19 patients admitted to the Yale New Haven Hospital between March 18 and May 9, and found a few key differences in how men and women responded to the disease biologically.

For starters, “male patients had a difficult time developing T cell immune response, whereas female patients had much better T cell activation,” explains Iwasaki, whose research was recently published in the journal Nature. T cells help protect the body from an infection and keep it from spreading.

Male patients who developed a diminished T cell response “ended up doing worse with the disease,” Iwasaki notes. “Whereas female patients were able to mount a T cell response and were able to control the virus infection.” T cell activation was especially low in older male patients, but not in older female patients, which may explain the disparity in deaths between men and women in certain age groups.

Another finding from the study: Men had higher levels of inflammatory proteins known as cytokines, which when released, tell the immune system to kick into gear. However, in severe cases of COVID-19, the body can release too many cytokines too quickly, causing the immune system to attack the body instead of the virus. This can lead to serious damage, including multi-organ failure, and “the earlier higher concentrations of cytokines in men make these outcomes more likely,” the researchers surmise. (A few of the women with higher cytokine levels also did worse in fighting off COVID-19.)

What the findings point to, Iwasaki says, is the need for a vaccine “to stimulate T cell response” in men. “If we actually have such a vaccine, men can mount T cell immunity and potentially recover from this infection much better.” Different treatment strategies for men and women may also be warranted, Iwasaki adds.

Additional research published since the start of the pandemic highlights sex differences, in everything from hormones and cell receptors to X chromosome-linked genetics, as potential reasons for why women are better able to fight off a coronavirus infection. Iwasaki says “knowing what kinds of responses are driving the disease and what's lacking in each sex and each age group would be much more informative in terms of appropriate treatment.”

"High-risk behaviors” and chronic conditions also play a role

While a biological component “is definitely there,” social and behavioral factors related to gender could also be tipping the trends in COVID-19 mortality, explains Derek M. Griffith, a professor of medicine and founding director for the Center for Research on Men's Health at Vanderbilt University.

For example, men are more likely than women to engage in “high-risk behaviors” that make them vulnerable to a coronavirus infection, Griffith and his colleagues write in a July CDC report. They have lower rates of handwashing, mask wearing and social distancing than women. And according to a recent Gallup poll, they are less worried about getting COVID-19, despite the fact that many low-paid essential jobs that increase exposure to the virus (food processing, transportation, delivery, etc.) are often filled by men.

What's more, men are more likely than women to smoke and to have heart disease and high blood pressure, and they are also more likely to be overweight or obese — all of which are factors that increase the risk for severe illness from a coronavirus infection.

Griffith says prevention efforts targeted specifically to men and women are critical in the fight against COVID-19. “We know that the one-size-fits-all approach doesn't usually work,” he adds. Decreasing barriers to testing and increasing access to preventive care for men with underlying conditions, for example, could help to close the gender gap of coronavirus-related hospitalizations and deaths.

So could tailored messages reinforcing the importance of public health approaches that help to slow the spread of the virus, Griffith says — especially in the absence of a vaccine.

"Regardless of sex, this virus can cause very severe disease, even in younger people. So until a vaccine is absolutely distributed, we still need to keep [up with] social distancing measures and masks and all the precautions,” Iwasaki adds.