Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection

Authors

Tanayott Thaweethai, Massachusetts General Hospital
Sarah E. Jolley, University of Colorado Anschutz Medical Campus
Elizabeth W. Karlson, Brigham and Women's Hospital
Emily B. Levitan, The University of Alabama at Birmingham
Bruce Levy, Harvard Medical School
Grace A. McComsey, Case Western Reserve University
Lisa McCorkell, Patient-Led Research Collaborative
Girish N. Nadkarni, Icahn School of Medicine at Mount Sinai
Sairam Parthasarathy, University of Arizona College of Medicine – Tucson
Upinder Singh, Stanford University School of Medicine
Tiffany A. Walker, Emory University School of Medicine
Caitlin A. Selvaggi, Massachusetts General Hospital
Daniel J. Shinnick, Massachusetts General Hospital
Carolin C.M. Schulte, Massachusetts General Hospital
Rachel Atchley-Challenner, Mass General Brigham
Leora I. Horwitz, NYU Grossman School of Medicine
Andrea S. Foulkes, Massachusetts General Hospital
George A. Alba, Massachusetts General Hospital
Radica Alicic, University of Washington
Natasha Altman, University of Colorado Anschutz Medical Campus
Khamal Anglin
Urania Argueta
Hassan Ashktorab, Howard University
Gaston Baslet, Brigham and Women's Hospital
Ingrid V. Bassett, Massachusetts General Hospital
Lucinda Bateman, Bateman Horne Center
Brahmchetna Bedi, Emory University School of Medicine
Shamik Bhattacharyya, Brigham and Women's Hospital
Marie Abele Bind, Massachusetts General Hospital
Andra L. Blomkalns, Stanford University
Hector Bonilla, Stanford University
Patricia A. Bush, Kaiser Foundation Health Plan of Georgia, Inc.
Mario Castro, University of Kansas Medical Center
James Chan, Massachusetts General Hospital

Document Type

Article

Publication Date

6-13-2023

Abstract

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

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