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Multicenter Study
. 2025 Aug 1;8(8):e2526506.
doi: 10.1001/jamanetworkopen.2025.26506.

Variability in Long COVID Definitions and Validation of Published Prevalence Rates

Lauren E Wisk  1 , Michelle L'Hommedieu  1 , Kate Diaz Roldan  1 , Imtiaz Ebna Mannan  2 , Erica S Spatz  3   4 , Robert A Weinstein  5   6 , Arjun K Venkatesh  3   7 , Michael Gottlieb  8 , Ryan Huebinger  9 , Kristin L Rising  10   11 , Juan Carlos C Montoy  12 , Kari A Stephens  13   14 , Robert M Rodriguez  15 , Mandy J Hill  9 , Kelli N O'Laughlin  16   17 , Nicole L Gentile  13   18   19 , Ahamed H Idris  20 , Shu-Xia Li  3 , Michelle Santangelo  8 , Efrat R Kean  10 , Samuel A McDonald  20   21 , Kristyn Gatling  5 , Joann G Elmore  1 ; INSPIRE Group
Collaborators, Affiliations
Multicenter Study

Variability in Long COVID Definitions and Validation of Published Prevalence Rates

Lauren E Wisk et al. JAMA Netw Open. .

Abstract

Importance: Long COVID definitions vary widely, and no consensus exists on how to accurately measure its prevalence, complicating both clinical care and research.

Objective: To assess long COVID prevalence using various definitions from published literature.

Design, setting, and participants: This prospective, multicenter cohort study used data from the longitudinal Innovative Support for Patients With SARS-CoV-2 Infections Registry (INSPIRE). Participants aged 18 years or older with symptoms suggestive of COVID-19 illness at the time of their index SARS-CoV-2 test enrolled at 8 sites across the US from December 11, 2020, through August 29, 2022, with follow-up surveys collected through February 28, 2023.

Exposure: Positive or negative SARS-CoV-2 test result at the time of acute symptoms.

Main outcomes and measures: Long COVID prevalence among INSPIRE participants with a positive vs negative index SARS-CoV-2 test, based on long COVID definitions in published literature. Secondary outcomes were sensitivity and specificity of published definitions compared with self-reported long COVID.

Results: A total of 4575 INSPIRE participants were included (mean [SD] age, 40.40 [14.58] years). Most were female (3013 of 4448 [67.7%]) and aged 18 to 49 years (3338 of 4541 [73.5%]). Applying 5 published definitions for long COVID yielded a prevalence that ranged from 30.84% (95% CI, 29.33%-32.40%) to 42.01% (95% CI, 40.37%-43.66%) at 3 months and 14.23% (95% CI, 13.01%-15.55%) to 21.94% (95% CI, 20.47%-23.47%) at 6 months postinfection; in the 5 comparator studies, reported prevalence of long COVID at 1 to 5 months postinfection ranged from 2.6% (≥84 days) to 47.4% (3-5 months) and at 6 or more months postinfection ranged from 10.0% (95% CI, 8.8%-11.0%) to 61.9% (6-11 months). Using participants' self-reported long COVID as a criterion standard, existing published definitions had low-to-moderate sensitivity (up to 66.32% [95% CI, 62.59%-69.90%] at 3 months and 45.53% [95% CI, 41.51%-49.60%] at 6 months) and high specificity (up to 81.29% [95% CI, 79.32%-83.15%] at 3 months and 94.26% [95% CI, 92.98%-95.37%]) at 6 months.

Conclusions and relevance: In this cohort study, variability in long COVID prevalence across published definitions highlights the need for a standardized, validated definition to improve clinical recognition and research comparability, ultimately guiding more accurate diagnosis and treatment strategies.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Wisk reported receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases outside the submitted work. Dr L’Hommedieu reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study and from the Patient-Centered Outcomes Research Institute and the California Breast Cancer Research Program outside the submitted work. Dr Venkatesh reported receiving grants from the SAEM Foundation and Centers for Medicare & Medicaid Services outside the submitted work. Dr Gottlieb reported receiving grants from the Bill and Melinda Gates Foundation and the Biomedical Advanced Research and Development Authority during the conduct of the study. Dr Rising reported receiving grants from the NIH, Abbott, Healgen, Prenosis, and MeMed outside the submitted work. Dr Montoy reported receiving grants from the Centers for Disease Control and Prevention (CDC), the Substance Abuse and Mental Health Services Administration, and the US Food & Drug Administration outside the submitted work. Dr Stephens reported receiving grants from the NIH outside the submitted work. Dr Rodriguez reported receiving funding from the National Institute of Allergy and Infectious Diseases and from Pfizer Inc during the conduct of the study. Dr O’Laughlin reported receiving funding from the NIH during the conduct of the study. Dr Gentile reported receiving grants from the Agency for Healthcare Research and Quality, National Center for Complementary and Integrative Health, and National Institute on Aging outside the submitted work and being codirector of a long COVID clinic at the University of Washington. Dr Idris reported receiving grants from the National Heart, Lung, and Blood Institute outside the submitted work and serving as an unpaid volunteer on both the American Heart Association Emergency Cardiovascular Care Committee and the clinical advisory board of Stryker Belfast, Inc. Dr Elmore reported serving as editor-in-chief of adult primary care topics for UpToDate and as director of the National Clinician Scholars Program at the University of California, Los Angeles. No other disclosures were reported.

Figures

Figure.
Figure.. Comparison of Long COVID Prevalence Among the INSPIRE Participants When Using 5 Different Published Definitions
The long COVID definition from each study was applied to eligible Innovative Support for Patients With SARS-CoV-2 Infections Registry (INSPIRE) participants who completed the surveys at 3 months and/or 6 months. The INSPIRE cohort eligible for the 3-month follow-up survey had 4575 participants and for both the 3- and 6-month surveys, 3897 participants. Prevalences were calculated based on persistence of 1 or more symptoms (constituting source definitions) at baseline and 3 months (for 3-month prevalence) and at baseline, 3 months, and 6 months (for 6-month prevalence). Error bars indicate 95% CIs. aPagen et al presented 6 definitions of long-term symptoms, but we chose to replicate definition 6 because we also defined long COVID as participants having COVID-19 symptoms after 3 months.
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