Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
Tanayott Thaweethai, Sarah E. Jolley, Elizabeth W. Karlson, Emily B. Levitan, Bruce D. Levy, Grace A. McComsey, Lisa McCorkell, Girish N. Nadkarni, Sairam Parthasarathy, Upinder Singh, Tiffany Walker, Caitlin Selvaggi, Daniel J. Shinnick, Carolin C. M. Schulte, Rachel Atchley-Challenner, Leora I. Horwitz, Andrea S. Foulkes, Judith A. Aberg, Natalie L. Adolphi, Shreya Ahirwar, Shifa Ahmed, Neera Ahuja, Masanori Aikawa, Almary Akerlundh, Teresa Akintonwa, Aseel Al‐Jadiri, Natalya Alekhina, Heather A. Algren, Akram N. Alshawabkeh, Nariman Ammar, Adit Anand, Brett R. Anderson, Lisa Aponte‐Soto, Judy L. Aschner, Mary Atha, Andrew M. Atz, Robin L. Aupperle, Mirna Ayache, Eduardo Azziz‐Baumgartner, L. Charles Bailey, Fiona C. Baker, Venkataraman Balaraman, Jennifer A. Bandy, Dithi Banerjee, Deanna M. Barch, James M. Bardes, Jackson Barlocker, R. Graham Barr, Arielle Baskin–Sommers, Sanjib Basu, Tracy A. Battaglia, Leah Castro Baucom, Carmen Beamon, Casey L. Beaty, Noam D. Beckmann, Jasmine A. Berry, Nahid Bhadelia, Daksh Bhargava, Sultana Bhuiyan, Jiang Bian, Christian Bime, James M. Bjork, Lora Black, Catherine A. Blish, Jason P. Block, Amanda Bogie, Dawn Bolliger, William J. Bonaventura, Seuli Bose‐Brill, Mary Bower, Andrew D. Boyd, Jerusha Boyineni, Steven B. Bradfute, Carolyn T. Bramante, M. Daniel Brannock, J. Douglas Bremner, Shari B. Brosnahan, Natalie C. Buchbinder, Elliott Bueler, Irina A. Buhimschi, Hülya Bükülmez, H. Timothy Bunnell, John B. Buse, Elizabeth A. Calhoun, Tingyi Cao, Michael D. Carrithers, Thomas W. Carton, Abigail Case, B.J. Casey, Faye Victoria C. Casimero, Lauren Castro, Teresa C. Cato, Patricia Ceger, Connie L. Cerullo, Linda Chang, A. Ann Chang, Praneeth Chebrolu, Yong Chen, Long‐Qing Chen, Benjamin K. Chen
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.