Nonmenopausal females aged 40 to 54 years have a 48% higher risk of developing long COVID compared to males in the same age group, while menopausal females show a slightly lower but still elevated risk, according to a recent study.
Researchers conducted a cohort study evaluating sex-based differences in the risk of long COVID among adults leveraging data from the Researching COVID to Enhance Recovery-Adult cohort. The study, published in JAMA Network Open, encompassed 12,276 participants aged 18 years and older across 83 U.S. sites, including Puerto Rico and Washington, DC, between October 2021 and July 2024.
Participants completed symptom surveys and underwent physical exams. Long COVID was defined based on a validated symptom-based scoring algorithm applied 6 months or more after SARS–CoV-2 infection. Propensity score matching accounted for demographic, clinical, and social determinants of health.
Among the participants, 73% were female (n = 8,969), and the mean age was 46 years (standard deviation = 15). Females demonstrated a significantly higher risk of long COVID than males across multiple models. In the primary full model, which adjusted for clinical and sociodemographic factors, the risk ratio (RR) for females was 1.31 (95% confidence interval [CI] = 1.06–1.62), noted first author Dimpy P. Shah, MD, PhD, of Long School of Medicine, University of Texas Health Science Center, San Antonio, and colleagues. In a reduced model including only age, race, and ethnicity, the RR increased to 1.44 (95% CI = 1.17–1.77).
Age and menopausal status modified the association. Among females aged 40 to 54 years, the RR for long COVID was 1.48 (95% CI = 1.19–1.84) compared with males of the same age group. Further stratification revealed that nonmenopausal females aged 40 to 54 years had a higher risk (RR = 1.45; 95% CI = 1.15–1.83), while the risk was attenuated for menopausal females (RR = 1.42; 95% CI = 0.99–2.03). In contrast, females aged 18 to 39 years had no significant difference in risk compared to males (RR = 1.04; 95% CI = 0.72–1.49).
Sensitivity analyses excluding pregnant participants (20% of females) and stratifying by hospitalization during initial infection, variant era, or comorbidities confirmed the robustness of the findings. Notably, comorbidities like myalgic encephalomyelitis/chronic fatigue syndrome—which are more common in females—mediated some risk differences.
The researchers emphasized the importance of investigating sex-specific mechanisms underlying long COVID, suggesting that factors such as age, hormonal status, and immune modulation may contribute to the observed differential risk.
Full disclosures can be found in the published study.