Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 2;8(1):e2455430.
doi: 10.1001/jamanetworkopen.2024.55430.

Sex Differences in Long COVID

Dimpy P Shah  1 , Tanayott Thaweethai  2   3 , Elizabeth W Karlson  4 , Hector Bonilla  5 , Benjamin D Horne  6   7 , Janet M Mullington  3   8 , Juan P Wisnivesky  9 , Mady Hornig  10   11 , Daniel J Shinnick  2 , Jonathan D Klein  12   13 , Nathaniel B Erdmann  14 , Shari B Brosnahan  15 , Joyce K Lee-Iannotti  16   17 , Torri D Metz  18 , Christine Maughan  11 , Ighovwerha Ofotokun  19 , Harrison T Reeder  2   3 , Lauren E Stiles  11   20 , Aasma Shaukat  15 , Rachel Hess  21   22 , Hassan Ashktorab  23 , Logan Bartram  9 , Ingrid V Bassett  24 , Jacqueline H Becker  9 , Hassan Brim  23 , Alexander W Charney  9 , Tananshi Chopra  25 , Rebecca G Clifton  26 , Steven G Deeks  27 , Kristine M Erlandson  28 , Daniel S Fierer  9 , Valerie J Flaherman  29   30 , Vivian Fonseca  31 , Jennifer C Gander  32   33 , Sally L Hodder  34 , Vanessa L Jacoby  27 , Pavitra Kotini-Shah  13 , Jerry A Krishnan  13 , Andre Kumar  5 , Bruce D Levy  4 , David Lieberman  35 , Jenny J Lin  9 , Jeffrey N Martin  30 , Grace A McComsey  36 , Talal Moukabary  37 , Megumi J Okumura  27 , Michael J Peluso  27 , Clifford J Rosen  38 , George Saade  39 , Pankil K Shah  1 , Zaki A Sherif  23 , Barbara S Taylor  1 , Katherine R Tuttle  40 , Alfredo E Urdaneta  41 , Julie A Wallick  42 , Zanthia Wiley  19 , David Zhang  43 , Leora I Horwitz  15 , Andrea S Foulkes  2   3 , Nora G Singer  36   44 ; RECOVER Consortium
Collaborators, Affiliations

Sex Differences in Long COVID

Dimpy P Shah et al. JAMA Netw Open. .

Erratum in

  • Errors in Supplement 2.
    [No authors listed] [No authors listed] JAMA Netw Open. 2025 Mar 3;8(3):e254888. doi: 10.1001/jamanetworkopen.2025.4888. JAMA Netw Open. 2025. PMID: 40080028 Free PMC article. No abstract available.

Abstract

Importance: A substantial number of individuals worldwide experience long COVID, or post-COVID condition. Other postviral and autoimmune conditions have a female predominance, but whether the same is true for long COVID, especially within different subgroups, is uncertain.

Objective: To evaluate sex differences in the risk of developing long COVID among adults with SARS-CoV-2 infection.

Design, setting, and participants: This cohort study used data from the National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER)-Adult cohort, which consists of individuals enrolled in and prospectively followed up at 83 sites in 33 US states plus Washington, DC, and Puerto Rico. Data were examined from all participants enrolled between October 29, 2021, and July 5, 2024, who had a qualifying study visit 6 months or more after their initial SARS-CoV-2 infection.

Exposure: Self-reported sex (male, female) assigned at birth.

Main outcomes and measures: Development of long COVID, measured using a self-reported symptom-based questionnaire and scoring guideline at the first study visit that occurred at least 6 months after infection. Propensity score matching was used to estimate risk ratios (RRs) and risk differences (95% CIs). The full model included demographic and clinical characteristics and social determinants of health, and the reduced model included only age, race, and ethnicity.

Results: Among 12 276 participants who had experienced SARS-CoV-2 infection (8969 [73%] female; mean [SD] age at infection, 46 [15] years), female sex was associated with higher risk of long COVID in the primary full (RR, 1.31; 95% CI, 1.06-1.62) and reduced (RR, 1.44; 95% CI, 1.17-1.77) models. This finding was observed across all age groups except 18 to 39 years (RR, 1.04; 95% CI, 0.72-1.49). Female sex was associated with significantly higher overall long COVID risk when the analysis was restricted to nonpregnant participants (RR, 1.50; 95%: CI, 1.27-1.77). Among participants aged 40 to 54 years, the risk ratio was 1.42 (95% CI, 0.99-2.03) in menopausal female participants and 1.45 (95% CI, 1.15-1.83) in nonmenopausal female participants compared with male participants.

Conclusions and relevance: In this prospective cohort study of the NIH RECOVER-Adult cohort, female sex was associated with an increased risk of long COVID compared with male sex, and this association was age, pregnancy, and menopausal status dependent. These findings highlight the need to identify biological mechanisms contributing to sex specificity to facilitate risk stratification, targeted drug development, and improved management of long COVID.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Thaweethai reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Karlson reported receiving grants from the NIH during the conduct of the study and outside the submitted work. Dr Horne reported receiving monies from Pfizer paid to the institution for consulting regarding risk scores; grants from the Task Force for Global Health for serving as site principal investigator (PI) for a COVID-19 study outside the submitted work; and unrelated grants from the Patient-Centered Outcomes Research Institute (PCORI) for being site PI. Dr Mullington reported receiving grants from the NIH during the conduct of the study and from the Open Medicine Foundation and the Patient Led Collaborative outside the submitted work. Dr Wisnivesky reported receiving personal fees or honoraria from PPD, Banook, and Sanofi and grants from Regeneron, Sanofi, and Axella outside the submitted work. Dr Klein reported receiving grants and salary support from the NIH to the University of Illinois at Chicago to support the RECOVER initiative and grants with no salary or other personal financial support from the NIH to Stanford University to support the RECOVER initiative during the conduct of the study. Dr Erdmann reported receiving grants from the University of Alabama at Birmingham during the conduct of the study; receiving personal fees from Prizer for serving on the data and safety monitoring board (DSMB) outside the submitted work; and having a patent for human neutralizing antibodies against SARS-CoV-2/COVID-19 licensed to PlantForm. Dr Brosnahan reported receiving grants from the NIH during the conduct of the study and from the Stony Wold-Herbert Foundation outside the submitted work. Dr Metz reported receiving grants from the NIH during the conduct of the study and from Pfizer for serving as site PI for a SARS-CoV-2 vaccination in pregnancy trial and a pharmacokinetics study of Paxlovid in pregnancy outside the submitted work. Dr Hess reported serving as a DSMB member for Astellas Pharma for fezolinetant trials outside the submitted work. Dr Brim reported receiving grants from Howard University during the conduct of the study. Dr Charney reported receiving grants from the NIH during the conduct of the study. Dr Clifton reported receiving grants from the NIH during the conduct of the study. Dr Deeks reported receiving nonfinancial support from Aerium and Eli Lily and personal fees from BioVie, Enanta Pharmaceuticals, and Pfizer during the conduct of the study and receiving personal fees from American Gene Technologies, AbbVie, Tendel, Renovaro, Hoopika, and Rora; grants from Gilead; and nonfinancial support from Vir and Caring Cross outside the submitted work. Dr Erlandson reported receiving grants from the NIH during the conduct of the study and receiving grants from Gilead and consulting for ViiV and Merck, with all payments to the university, outside the submitted work. Dr Fierer reported receiving grants from the NIH paid to the institution during the conduct of the study and grants from Gilead and Merck paid to the institution outside the submitted work. Dr Flaherman reported receiving grants from the NIH during the conduct of the study. Dr Hodder reported receiving grants from the NIH during the conduct of the study. Dr Jacoby reported receiving grants from the NIH during the conduct of the study. Dr Kotini-Shah reported receiving a pilot grant from the American Heart Association and grants from the National Heart, Lung, and Blood Institute (NHLBI) and National Institute of Neurological Disorders and Stroke outside the submitted work. Dr Krishnan reported receiving grants from the NIH paid to the institution during the conduct of the study; having a research contract from the PCORI for a chronic obstructive pulmonary disease (COPD) clinical trial and grants from the American Lung Association and COPD Foundation outside the submitted work; receiving personal fees from AstraZeneca, paid to the institution, for serving as a consultant for monoclonal antibodies for asthma outside the submitted work; receiving personal fees from CereVu for serving as a medical consultant for a medical device for dyspnea, paid to the institution, outside the submitted work; receiving personal fees from BData, Inc, for serving as a consultant for a severe asthma registry outside the submitted work; receiving personal fees from Verona Pharma, PLC, for serving on the advisory board outside the submitted work; receiving personal fees from the American Board of Internal Medicine for serving as a consultant for board certification exam questions outside the submitted work; receiving personal fees from DynaMed for serving as a consultant for reviewing topics related to pulmonary medicine outside the submitted work; and serving unpaid on the board of directors of the Global Initiative for Asthma and the Respiratory Health Association. Dr Levy reported receiving grants from the NIH during the conduct of the study and personal fees from Merck outside the submitted work. Dr Martin reported receiving grants from the NIH during the conduct of the study. Dr McComsey reported receiving personal fees from Merck, Gilead, and GSK for serving as a consultant and grants from Pfizer, RedHill, and Roche outside the submitted work. Dr Peluso reported receiving grants from the NHLBI, NIH during the conduct of the study and receiving personal fees from Gilead Sciences and AstraZeneca and nonfinancial support from Aerium Therapeutics outside the submitted work. Dr P. Shah reported receiving grants from the National Center for Advancing Translational Sciences (NCATS), NIH during the conduct of the study. Dr Sherif reported receiving grants from the NIH during the conduct of the study. Dr Tuttle reported receiving grants from the NHLBI, NIH during the conduct of the study. Dr Wallick reported receiving grants from the NIH during the conduct of the study. Dr Horwitz reported receiving grants from the NHLBI during the conduct of the study. Dr Foulkes reported receiving grants from the NIH during the conduct of the study. Dr Singer reported receiving grants from Case Western Reserve University and the MetroHealth System during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. Application of Inclusion and Exclusion Criteria to Define the Study Cohort
RECOVER indicates Researching COVID to Enhance Recovery; WHO, World Health Organization. aThe reinfection window for exclusion was 30 days prior to and 7 days after the visit. bParticipants who completed the visit without reaching the end of the visit window are included in this count.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. World Health Organization. WHO COVID-19 dashboard. Accessed September 14, 2024. https://covid19.who.int/region/amro/country/us
    1. Sivan M, Taylor S. NICE guideline on long COVID. BMJ. 2020;371:m4938. doi:10.1136/bmj.m4938 - DOI - PubMed
    1. Demko ZO, Yu T, Mullapudi SK, et al. . Two-year longitudinal study reveals that long COVID symptoms peak and quality of life nadirs at 6-12 months postinfection. Open Forum Infect Dis. 2024;11(3):ofae027. doi:10.1093/ofid/ofae027 - DOI - PMC - PubMed
    1. Haslam A, Olivier T, Prasad V. The definition of long COVID used in interventional studies. Eur J Clin Invest. 2023;53(8):e13989. doi:10.1111/eci.13989 - DOI - PubMed
    1. Dessie ZG, Zewotir T. Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423 117 patients. BMC Infect Dis. 2021;21(1):855. doi:10.1186/s12879-021-06536-3 - DOI - PMC - PubMed

Publication types