People whose sex is male have a greater risk of developing severe Covid-19 infections and ultimately dying from the disease. Not only is that a trend doctors have observed since the beginning of the pandemic, it’s also the finding of a recent study that pooled data from over 3 million people from 47 countries. The paper, published in December in the journal Nature Communications, found that males were 2.84 times more likely to be admitted to the intensive care unit and 1.39 times more likely to die from Covid-19 than females. Notably, males and females had similar rates of infection with SARS-CoV-2, so the differences didn’t stem from men’s greater exposure to the virus but more serious outcomes once they were infected.
“When I see those kinds of epidemiological data that cut across countries, that cut across societal cultural norms, and within countries are cutting across age, that’s when I think there’s something biological going on,” says Sabra Klein, PhD, a professor at the Johns Hopkins Bloomberg School of Public Health.
The question is, what?
T cells and cytokines
One potential answer involves the body’s immune response.
A study published last summer in the journal Nature found that men and women have different immune responses to Covid-19, which influenced how severe their infections were. To research this, Yale professor of immunobiology Akiko Iwasaki, PhD, and her team took blood samples from people who showed up to the hospital with Covid-19 and then followed them to see how they progressed. The scientists discovered that, compared to women, men had lower activity of T cells — immune cells necessary to both fight off the virus and help produce antibodies. What’s more, men with the lowest T cell activity went on to have more severe disease.
In contrast, men had higher levels of two specific cytokines — immune proteins — than women. These cytokines, called IL-8 and IL-18, are signals of a hyperactive immune response that can cause inflammation and tissue damage. Interestingly, when women had elevated levels of these same inflammatory immune proteins, they developed more severe cases of Covid-19…