Study details

For the study, which was part of the RECOVER study funded by NIH, researchers analyzed data on more than 12,000 people from across 33 states, as well as Puerto Rico and Washington, D.C. These patients, who underwent medical exams and completed surveys between October 2021 and July 2024, reported whether they contracted COVID-19 and if their symptoms persisted.

The researchers found that female participants in the study had a 31% higher risk of developing long COVID following an infection with the coronavirus than the male participants.

They also found that women between the ages of 40 and 54 who were not menopausal had a 45% higher risk of developing long COVID than men in the same age group, and women ages 55 and older had a 34% increased risk of developing long COVID.

However, women ages 40 to 54 who had already experienced menopause and women ages 18 to 39 saw no significant difference in long COVID risk compared to men in the same age groups.

Discussion

According to Dimpy Shah, an assistant professor of population health sciences at the Joe R. and Teresa Lozano Long School of Medicine at the University of Texas Health Science Center and lead author of the study, the results suggest that hormones involved in menopause, fertility, and pregnancy could play a role in someone's risk of developing long COVID — and could be protective factors against the condition.

Estrogen levels in women tend to drop during menopause, Shah said, and while adult women under 40 have high estrogen levels, they also tend to have high levels of progesterone, a hormone that helps balance and regulate estrogen in the body. This is especially the case if they're pregnant.

Estrogen and testosterone both interact with the immune system in ways that aren't fully understood, but, according to the Washington Post, experts say higher levels of estrogen could be associated with chronic longer-term immune responses. This might explain why women are nearly twice as likely as men to be diagnosed with autoimmune diseases.

Iwasaki added that some of her long COVID patients have seen their symptoms improve while taking low-dose testosterone treatments, explaining that testosterone helps regulate the immune system in women and prevents it from being overactive.

The study also found that men and women with long COVID experienced different types of symptoms, which Iwasaki said mirrored the results of research she's done and suggests that in some cases, long COVID in men and women could be different but related conditions.

"When I first saw the study, I thought, 'Wow, a lot of the differences they're seeing are exactly what we see in our work,'" Iwasaki said. "This is revealing more subsets of long COVID that may be triggered by different causes."

According to Catherine Blish, an immunologist and professor of medicine at Stanford University School of Medicine, comparing long COVID in men and women is a good way to understand the disease because there can be such "dramatic differences" in the immune responses between the two.

Blish said that women with long COVID seem to experience more of an autoimmune response. Blish's own research indicated that while women who developed long COVID tended to have normal-looking immune system responses to kill the coronavirus, they then had increased inflammation, even after the virus was eliminated, compared to women who recovered and were able to resolve the inflammation.

Women with long COVID also had increased levels of Xist, a gene that's associated with autoimmune disease, compared to women who didn't develop the condition, Blish said.

In comparison, men with long COVID seem to have a harder time killing the virus in the first place, suggesting that their symptoms could be a result of a more persistent infection, Blish added.

Both immune responses need to be studied further, Blish said, but the study results suggest that the prevention and treatment of long COVID could vary significantly in men and women.

"Even if they end up in the same place, the underlying drivers of disease can be quite different," she said.