Data from COVID-19 cases around the world suggest that the new coronavirus hits men harder than women.
Differences in men’s and women’s immune responses to the virus may help explain why.
In a new study, researchers found when infected by the new coronavirus, women may mount a more potent adaptive immune response than do men.
By comparison, the male immune response appears to progress less effectively, fostering inflammation that’s harmful to the body.
This study is the first to delve into sex differences in how the immune system defends itself against the virus SARS-CoV-2.
It could help explain why men can fall more severely ill.
The research was conducted by a team at Howard Hughes Medical Institute.
Since SARS-CoV-2 emerged in Wuhan, China, researchers have shown that the virus is hardly indiscriminate.
It poses more of a threat to certain categories of people, including the elderly, those with certain medical conditions, and African Americans.
And early reports from Wuhan, the epicenter of the pandemic, indicated that infections hit men harder, a trend later confirmed elsewhere in the world.
The degree of this disparity between men and women varies.
Data from the US Centers for Disease Control and Prevention through early June shows that men account for 54 percent of COVID-19-related deaths.
Meanwhile, an analysis of data from more than 1,000 infected Chinese patients found that 2.4 times more men died than women.
Experts have suggested a long list of potential contributors to this disparity, including male sex hormones, men placing less priority on their health, and levels of a molecule the virus needs to invade cells.
In the study, the team focused on the immune responses of 93 COVID-19 patients admitted to Yale New Haven Hospital.
They tested how men and women’s immunological differences might play out in COVID-19.
Using blood, saliva, and nasal swabs collected from hospital patients, the team concentrated primarily on a group of men and women who had the moderate illness.
They found there was a big contrast between how women respond to the virus that causes COVID-19 and the way men respond.
The researchers identified a difference originating in the immune system’s two layers of defense. When a viral infection begins, the first layer responds rapidly.
Infected cells sound the alarm, sending out cytokine proteins that summon immune cells to fight the infection.
Although a necessity, this process, known as inflammation, can be dangerous if not controlled. In COVID-19, runaway inflammation known as a cytokine storm can cause death.
Within days, the immune system’s second layer of defense kicks in. This finely-tuned response enlists so-called T and B cells that learn to recognize the enemy and eradicate it.
The team found that female patients had more of the virus-fighting T cells, while men had higher levels of inflammation-promoting cytokines.
This suggests men are stuck in the first layer of the immune response. Because men don’t properly activate the second, more targeted defense system, inflammation appears to ramp up, she explains.
The team also tracked the severity of the patients’ illnesses. Men whose condition remained stable generated strong T cell responses, not unlike the women’s.
However, men lacking a strong T-cell response fared worse—they needed to move to the intensive care unit or use a ventilator to breathe.
Some of the women struggled, too, but for a different reason: they failed to bring their cytokine signaling under control.
Overall, the results suggest that women fare better than men because of their T cells. While men’s T cell levels declined with age, levels remained strong for women into their 90s.
These discoveries hint that male patients may benefit from treatments to enhance their T cells.
The sex-based differences revealed in this study suggest that treatments could be tailored to better suit male versus female patients.
One author of the study is Howard Hughes Medical Institute Investigator Akiko Iwasaki.
The study is published in Medrxiv.
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