Clues to Why COVID-19 Hits Men Harder Than Women

WEDNESDAY, Aug. 26, 2020 (HealthDay News) -- Since the pandemic began, it's been clear that men are more vulnerable to getting a severe case of COVID-19 compared to women.

Now, researchers say they've uncovered significant differences in how male and female immune systems respond to the new coronavirus may help explain why men are more likely than women to have severe COVID-19 and to die from the illness.

Worldwide, men account for 60% of COVID-19 deaths, noted a team from Yale University, in New Haven, Conn.

"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," study senior author Akiko Iwasaki said in a Yale news release. She's professor of immunobiology and molecular, cellular and development biology at the university.

The findings "suggest we need different strategies to ensure that treatments and vaccines are equally effective for both women and men," according to Iwasaki, who's also an investigator at Yale's Howard Hughes Medical Institute.

In the new study, her team analyzed nasal, saliva and blood samples from COVID-19 patients and compared them to samples from people who weren't infected by the new coronavirus.

The patients were then followed over time to determine whether initial immune responses differed in patients who recovered from the disease and those who went on to develop more severe illness.

Men and women had significant differences in immune responses during the early phases of coronavirus infection, the researchers said. Their report is scheduled for publication in the Aug. 28 issue of Nature.

For example, men had higher levels of several types of inflammatory proteins called cytokines, which are deployed by the immune system early in an infection to create inflammation as a physical barrier against invading pathogens, the researchers explained.

However, patients with severe COVID-19 become very ill precisely because they develop this excessive build-up of cytokines. This "cytokine storm" causes fluid build-up in the lungs, which reduces oxygen levels and potentially leads to shock, tissue damage and multiple organ failure, the Yale team explained.

Men are at increased risk for these serious problems due to their earlier higher concentrations of cytokines.

In contrast, women had stronger activation than men of T-cells, another component of the immune system. T-cells are white blood cells that can recognize individual invading viruses and then eliminate them.

Poor T-cell responses in men also led to more severe COVID-19, and women who had highly elevated cytokine levels also had more serious illness, the study authors said.

The investigators also found that older men -- but not older women -- had significantly worse T-cell responses than younger patients.

"These findings answer questions about COVID-19 that point the way toward a more effective, targeted response to this disease," Carolyn Mazure, director of women's health research at Yale University, said in the news release. "As Dr. Iwasaki and her colleagues conclude, researchers racing to develop treatments and vaccines should consider separate strategies for women and men so that everyone can benefit," she added.

Dr. Marcus Altfeld is an immunologist at the Heinrich Pette Institute and at the University Medical Center Hamburg-Eppendorf in Germany. He told The New York Times, "You could imagine scenarios where a single shot of a vaccine might be sufficient in young individuals or maybe young women, while older men might need to have three shots of vaccine."

Reading over the Yale findings, Dr. Amesh Adalja, an infectious disease expert and senior scholar at the Center for Health Security at Johns Hopkins University, in Baltimore, agreed that "understanding these responses [based on sex or age] and learning how to fine-tune them to generate better outcomes will be an important task."

According to Adalja, "We are increasingly seeing that a one-size-fits-all strategy is not always possible, and precision medicine -- based on each individual's unique characteristics -- is likely the best approach" to fighting severe COVID-19.

More information

The U.S. Centers for Disease Control and Prevention has more on COVID-19.