Why Men Are More Likely To Suffer A Severe Case Of Covid-19

Colorized scanning electron micrograph of an apoptotic cell (blue) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. NIAID

Covid-19 doesn’t care who it infects. However, there’s a fair amount of evidence that shows men, especially older men, are more vulnerable to a severe infection than women. 

In a new study, researchers at Yale Unversity investigated this apparent sex-based difference and revealed a possible explanation for why men are more likely than women to suffer severe and deadly cases of Covid-19.

It has to do with key differences in the immune response during the early phases of infection. Reported in the journal Nature this week, the small study saw the team assess 98 patients (average age of 61 to 64 years of age) admitted to the Yale New Haven Hospital in the United States with mild to moderate confirmed cases of Covid-19. Using nasal, saliva, and blood samples from the patients and non-infected control subjects, the team looked at how the body mounted an immune response to the disease. 

They found that women appear to produce a “more robust and sustained” T-cell response than male patients. T-cells are a type of white blood cell that serve as important soldiers of the immune system, attacking specific foreign particles. Better T-cell responses, therefore, tend to be associated with better disease outcomes. 

Along with this, men were found to produce more of a different type of cell known as cytokines, signaling molecules that recruit immune cells to sites of inflammation. Although part of the immune system, their role can be counterproductive in severe Covid-19 cases because of what’s referred to as a “cytokine storm.” This is when the immune system overreacts in an attempt to control the infection, releasing too many pro-inflammatory cytokines, which leads to hyperinflammation. Excessive inflammation can then cause fluid to build up in the lungs, tissue damage, multiple organ failure, and a bunch of other problems. 

So, in sum: Women tend to produce more T-cells, while men tend to produce more cytokines. 

The researchers say this knowledge could be used by doctors to tailor their treatments for people with severe Covid-19. For example, men may benefit from therapies that elevate T-cell responses, while women may benefit from therapies that dampen early innate immune responses.

“We now have clear data suggesting that the immune landscape in COVID-19 patients is considerably different between the sexes and that these differences may underlie heightened disease susceptibility in men,” senior study author Akiko Iwasaki, a Waldemar Von Zedtwitz Professor of Immunobiology and Molecular, Cellar and Development Biology, and an investigator of the Howard Hughes Medical Institute, said in a statement

“Collectively, these data suggest we need different strategies to ensure that treatments and vaccines are equally effective for both women and men.”

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