FEMALES are at significantly higher risk of developing long COVID compared to males, according to a recent cohort study involving over 12,000 participants. The study, conducted as part of the National Institutes of Health (NIH) RECOVER-Adult cohort, highlights age, pregnancy, and menopause as critical factors influencing these disparities, providing new insights into the biologically distinct trajectories of long COVID.
Researchers analyzed data from 83 sites across 33 U.S. states, Washington, D.C., and Puerto Rico, focusing on individuals 6 months or more after their initial SARS-CoV-2 infection. Among the participants, 73% of whom were female, the risk of long COVID was markedly higher in females (relative risk [RR]: 1.31-1.44), with particularly notable differences emerging among those aged 40 to 55.
The findings revealed that females aged 40 to 54 years had an elevated risk of long COVID regardless of menopausal status. For menopausal participants, the relative risk was 1.42, while nonmenopausal individuals exhibited an RR of 1.45 compared to males in the same age group. Pregnant individuals were excluded from this subgroup analysis, emphasizing the nuanced risk posed to nonpregnant people.
Interestingly, this sex-based disparity in long COVID risk was less pronounced in younger adults aged 18 to 39, with no statistically significant differences observed in that cohort.
The study underscores the importance of understanding sex-specific biological mechanisms to better stratify long COVID risk and inform targeted therapeutic approaches. Long COVID—defined through self-reported, symptom-based questionnaires—remains a persistent challenge, with many patients experiencing debilitating symptoms that affect their quality of life and functional status.
The research team emphasizes the critical need to develop interventions tailored to address these sex-specific risks, particularly for middle-aged females, who seem most vulnerable. As long COVID continues to strain healthcare systems worldwide, these findings could guide improved patient management and more equitable care strategies.
Reference: Shah DP et al. Sex Differences in Long COVID. JAMA Netw Open. 2025;8(1):e2455430.