Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort

Tanayott Thaweethai, Sarah E. Donohue, Jeffrey N. Martin, Mady Hornig, Jarrod M. Mosier, Daniel J. Shinnick, Hassan Ashktorab, Ornina Atieh, Andra Blomkalns, Hassan Brim, Yu Chen, Melissa M. Cortez, Nathan B. Erdmann, Valerie Flaherman, Paul Goepfert, Jason D. Goldman, Naomi M. Hamburg, Jenny E. Han, James R. Heath, Vanessa Jacoby, Sarah E. Jolley, J. Daniel Kelly, Sara W. Kelly, C. Kim, Jerry A. Krishnan, Rebecca Letts, Emily B. Levitan, Matthew E. Modes, Grace A. McComsey, Torri D. Metz, Janet M. Mullington, Igho Ofotokun, Megumi J. Okumura, Claudia Castillo Paredes, Thomas F. Patterson, Michael J. Peluso, Rebecca Reece, Zaki A. Sherif, Hyagriv N. Simhan, Christopher Simmons, Upinder Singh, Barbara S. Taylor, Brittany D. Taylor, Joel D. Trinity, Andrea B. Troxel, Paul J. Utz, Andrew J. Vasey, Elisheva Weinberger, Zanthia Wiley, Juan Wisnivesky, Lynn M. Yee, Leora Horwitz, Andrea S. Foulkes and Bruce D. Levy ()
Additional contact information
Tanayott Thaweethai: Massachusetts General Hospital Biostatistics
Sarah E. Donohue: University of Illinois College of Medicine Peoria
Jeffrey N. Martin: University of California San Francisco
Mady Hornig: or Community Advocate Representative
Jarrod M. Mosier: Department of Emergency Medicine University of Arizona College of Medicine-Tucson
Daniel J. Shinnick: Massachusetts General Hospital Biostatistics
Hassan Ashktorab: Howard University College of Medicine
Ornina Atieh: Case Western Reserve University
Andra Blomkalns: Stanford University School of Medicine
Hassan Brim: Howard University College of Medicine
Yu Chen: NYU Grossman School of Medicine
Melissa M. Cortez: University of Utah
Nathan B. Erdmann: University of Alabama at Birmingham
Valerie Flaherman: University of California San Francisco
Paul Goepfert: University of Alabama at Birmingham
Jason D. Goldman: Providence Swedish Medical Center
Naomi M. Hamburg: Boston University Chobanian and Avedisian School of Medicine
Jenny E. Han: Emory University School of Medicine
James R. Heath: Institute for Systems Biology
Vanessa Jacoby: University of California San Francisco
Sarah E. Jolley: University of Colorado Anschutz Medical Campus
J. Daniel Kelly: University of California San Francisco
Sara W. Kelly: University of Illinois College of Medicine Peoria
C. Kim: or Community Advocate Representative
Jerry A. Krishnan: University of Illinois Chicago
Rebecca Letts: or Community Advocate Representative
Emily B. Levitan: University of Alabama at Birmingham School of Public Health
Matthew E. Modes: Cedars-Sinai Medical Center
Grace A. McComsey: Case Western Reserve University
Torri D. Metz: University of Utah Health
Janet M. Mullington: Beth Israel Deaconess Medical Center
Igho Ofotokun: Emory University School of Medicine
Megumi J. Okumura: University of California San Francisco
Claudia Castillo Paredes: University of Texas Health Science Center at San Antonio
Thomas F. Patterson: University of Texas Health Science Center at San Antonio
Michael J. Peluso: San Francisco
Rebecca Reece: West Virginia University School of Medicine
Zaki A. Sherif: Howard University College of Medicine
Hyagriv N. Simhan: University of Pittsburgh School of Medicine
Christopher Simmons: University of Kentucky College of Medicine
Upinder Singh: University of Iowa Carver College of Medicine
Barbara S. Taylor: University of Texas Health Science Center at San Antonio
Brittany D. Taylor: or Community Advocate Representative
Joel D. Trinity: University of Utah
Andrea B. Troxel: NYU Grossman School of Medicine
Paul J. Utz: Stanford University School of Medicine
Andrew J. Vasey: University of Nebraska Medical Center
Elisheva Weinberger: MetroHealth Medical Center
Zanthia Wiley: Emory University School of Medicine
Juan Wisnivesky: Icahn School of Medicine at Mount Sinai
Lynn M. Yee: Northwestern University Feinberg School of Medicine
Leora Horwitz: NYU Grossman School of Medicine
Andrea S. Foulkes: Massachusetts General Hospital Biostatistics
Bruce D. Levy: Harvard Medical School

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract Longitudinal trajectories of Long COVID remain ill-defined, yet are critically needed to advance clinical trials, patient care, and public health initiatives for millions of individuals with this condition. Long COVID trajectories were determined prospectively among 3,659 participants (69% female; 99.6% Omicron era) in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Adult Cohort. Finite mixture modeling was used to identify distinct longitudinal profiles based on a Long COVID research index measured 3 to 15 months after infection. Eight longitudinal profiles were identified. Overall, 195 (5%) had persistently high Long COVID symptom burden, 443 (12%) had non-resolving, intermittently high symptom burden, and 526 (14%) did not meet criteria for Long COVID at 3 months but had increasing symptoms by 15 months, suggestive of distinct pathophysiologic features. At 3 months, 377 (10%) met the research index threshold for Long COVID. Of these, 175 (46%) had persistent Long COVID, 132 (35%) had moderate symptoms, and 70 (19%) appeared to recover. Identification of these Long COVID symptom trajectories is critically important for targeting enrollment for future studies of pathophysiologic mechanisms, preventive strategies, clinical trials and treatments.

Date: 2025
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DOI: 10.1038/s41467-025-65239-4

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