Gene that might shield men from severe COVID-19 found

The finding appears to work only until age 74, but a new study has identified a gene variant that protects men from from severe illness and death when COVID-19 lands them in the hospital.

The protective gene appears to help tamp down inflammation, researchers say. It is an interleukin-1 receptor antagonist (1L1RN) variant.

While inflammation is a normal response to infection, if left unchecked, it can damage tissues as part of many diseases, including severe cases of COVID-19.

"Our study results show that among hospitalized patients, while women are still overall less likely than men to die from COVID-19, those men age 74 and younger who possess the IL1RN gene variant rs419598 are much less likely to suffer the severe inflammation tied to SARS-CoV-2 infection and less likely to die from the disease," said study co-author Mukundan Attur, an associate professor of medicine at NYU Langone Health in New York City.

The study found that 124 men (aged 19-74) who had the gene variant were 80% less likely to die from COVID. They were also less likely to become severely ill after being hospitalized with the virus.

Researchers from NYU Grossman School of Medicine called their findings noteworthy because more men than women die from COVID-19. The gene variant appears to protect only men up to about age 74, but not beyond that as the chronic illnesses of aging take hold, they said.

For the study, researchers obtained blood samples from nearly 2,600 men and women hospitalized for COVID-19 at NYU Langone's Tisch Hospital in Manhattan between March 2020 and March 2021.

More than half were 60 or older and obese, putting them at higher risk of death from COVID-19. In all, 240 men and 157 women in the study died from their disease.

Researchers found that average blood levels of an inflammation-fighting protein coded by 1L1RN were 14 times higher in hospitalized men than in healthy male controls.

While they were 10 times higher in 178 hospitalized women than in healthy women, researchers said they did not result in a statistically significant reduction in death risk for women.

Senior study author Dr. Steven Abrahamson, a rheumatologist who serves as chairman of the Department of Medicine at NYU Langone, said the finding points to a pathway to prevent the severe inflammation often seen in COVID-19.

More study is needed to learn whether IL-1-inhibiting therapies such as anakinra, canakinumab and rilonacept are effective against COVID-19, he said.

He plans to investigate whether the IL-1 pathway contributes to Long COVID, the constellation of symptoms that persist months after initial infection.

Abrahamson said the new study adds to evidence about the underlying biology that contributes to gender differences in death rates from COVID-19.

The findings were published Wednesday in The Journal of Infectious Diseases.

More information

The journal Social Science & Medicine has more about gender-related differences in COVID care and survival.