Females have a 31% higher associated risk of developing long COVID, with women aged 40 to 55 years having the highest propensity, according to a study led by The University of Texas Health Science Center at San Antonio (UT Health San Antonio) funded by the National Institutes of Health.

The findings are part of a nationwide initiative launched by NIH, called Researching COVID to Enhance Recovery, or RECOVER, to understand the long-term health effects of COVID-19.

The latest study followed 12,276 participants over time to identify the risk of developing long COVID, and found females with a “risk ratio” of 1.31 compared with males, equating to 31% higher associated risk – even when considering factors like race, ethnicity, COVID variant, severity of COVID infection and other non-medical social factors that affect health.

The risk among females for developing long COVID was dependent on age, pregnancy and menopausal status.

These findings show that patients and health care teams should consider the differences in long COVID risk as it relates to sex assigned at birth. Understanding these differences can help us recognize and treat patients with long COVID more effectively.”

Dimpy Shah, MD, PhD, assistant professor of population health sciences with the Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio

Shah is corresponding author of the study, titled, “Sex Differences in Long COVID,” published Jan. 22, 2025, in JAMA Network Open.

“This important study from the RECOVER cohort identifies risk factors for long COVID that are critical in providing insights for prevention and treatment of this often debilitating disease,” said Thomas Patterson, MD, MACP, professor of medicine and chief of the Division of Infectious Diseases with the Long School of Medicine at UT Health San Antonio, and principal investigator for PREVAIL South Texas, the UT Health San Antonio RECOVER hub.

Largest cohort study for long COVID

Worldwide, SARS-CoV-2, a strain of coronavirus that causes COVID-19, has infected more than 700 million people, with an estimated 7 million deaths, the study notes. Although many individuals recover from acute COVID-19, a substantial portion experience long-term effects, called long COVID, or post-COVID condition.

Other post-viral and autoimmune conditions have a female predominance, but whether the same is true for long COVID, especially within different subgroups, has been uncertain.

Numerous studies had shown that males have more severe acute COVID-19 cases and higher mortality than females. However, emerging literature suggested that females may be at greater risk for new and persisting symptoms following initial infection.

Studies had yet to fully account for factors that may distort the true estimate of biological sex-related risk – like age, menstrual status, comorbidities, vaccination status, variants of concern, severity of acute illness and differential engagement in health care. Some studies relied upon relatively small sample sizes or those lacking ethnic or racial diversity.

The RECOVER researchers set out to evaluate sex differences in the risk of developing long COVID among adults with SARS-CoV-2 infections, accounting for distorting factors and representing the largest cohort to date followed up in a natural history study of long COVID. The cohort study used data from the NIH RECOVER-Adult cohort, consisting of individuals enrolled in and prospectively followed up at 83 sites in 33 states, Washington, D.C., and Puerto Rico.

Data was examined from participants enrolled from Oct. 29, 2021, to July 5, 2024, who had a qualifying study visit 6 months or more after their initial COVID-19 infection. Gender was defined as self-reported sex assigned at birth.

The scientists measured development of long COVID using a self-reported symptom-based questionnaire and scoring guideline at the first study visit. They used propensity score matching to estimate risk ratios and risk differences. The full model included demographic and clinical characteristics, and social determinants of health, with a reduced model including only age, race and ethnicity.

The full model found the 31% higher risk for females, with a mean age of infection at 46 years. Among participants aged 40 to 54 years, the risk was even higher – at 42% higher in menopausal participants and 45% higher in non-menopausal female participants, compared with male participants.

“This study gives us new knowledge and builds on other studies that also looked at sex assigned at birth and long COVID,” Shah said. “Because of the size of the RECOVER study and the diversity of participants, we had a special opportunity to look at sex assigned at birth while also considering things like vaccination status, autoimmune disease, diabetes, BMI and COVID variant.

“We hope this encourages other researchers to explore why there are differences in the risk of developing long COVID based on your assigned sex at birth,” she said.

Other researchers in the study also are with the Long School at UT Health San Antonio, as well as Massachusetts General Hospital Biostatistics; Harvard Medical School; Brigham and Women’s Hospital; Stanford University; Intermountain Health; Beth Israel Deaconess Medical Center; Icahn School of Medicine at Mount Sinai; Columbia University; RECOVER Patient, Caregiver or Community Representative, New York; University of Illinois Chicago; University of Alabama at Birmingham; NYU; University of Arizona; University of Utah Health; Emory University; University of Utah; Stony Brook University; Howard University; Cedars-Sinai Medical Center; and The George Washington University.

Also, University of California San Francisco; University of Colorado-Anschutz Medical Campus; Tulane University Health Sciences Center; Kaiser Permanente of Georgia; Centre College; West Virginia University; Banner Health; Case Western Reserve University; MaineHealth Institute for Research; The University of Texas Medical Branch-Galveston; Providence Inland Northwest Health; Swedish Health Services; University of Chicago; and MetroHealth Medical Center.