Timing of Long COVID Improvement in Prospectively Followed RECOVER-Adult Participants

Reeder HT 1 , Donohue SE 2 , Martin JN 3 , Hornig M 4 , Mosier JM 5 , Ashktorab H 6 Show all authors , Atieh O 7 , Blomkalns AL 8 , Brim H 6 , Chen Y 9 , Cortez MM 10 , Erdmann NB 11 , Fang M 12 , Flaherman VJ 13 , Goepfert P 11 , Goldman JD 14 , Hamburg NM 15 , Han JE 16 , Heath JR 17 , Jacoby VL 18 , Jolley SE 19 , Kelly JD 3 , Kelly SW 2 , Kim C 20 , Krishnan JA 21 , Letts RJ 20 , Levitan EB 22 , Modes ME 23 , McComsey GA 7 , Metz TD 24 , Mullington JM 25 , Ofotokun I 26 , Okumura MJ 27 , Castillo Paredes C 28 , Patterson TF 28 , Peluso MJ 29 , Reece R 30 , Selvaggi CA 12 , Sherif ZA 6 , Simhan HN 31 , Singh U 32 , Taylor BS 28 , Taylor BD 20 , Thaweethai T 1 , Trinity JD 33 , Troxel AB 9 , Utz PJ 34 , Vasey AJ 35 , Weinberger E 7 , Wiley Z 26 , Wisnivesky JP 36 , Yee LM 37 , Horwitz LI 38 , Foulkes AS 39 , Levy BD 40 , RECOVER-Adult Cohort

Affiliations 

  • 1 Massachusetts General Hospital, Biostatistics, and Harvard Medical School, Harvard University, Boston, Massachusetts (H.T.R., T.T.)
  • 2 Department of Psychiatry and Behavioral Medicine, Illinois Research Network (ILLInet) Hub, and Division of Research Services, University of Illinois College of Medicine Peoria, Peoria, Illinois (S.E.D., S.W.K.)
  • 3 Division of Clinical Epidemiology and Health Services Research, Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California (J.N.M., J.D.K.)
  • 4 RECOVER Initiative, New York, and The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York (M.H.)
  • 5 Departments of Emergency Medicine and Medicine, University of Arizona, and University of Arizona College of Medicine-Tucson, Tucson, Arizona (J.M. Mosier)
  • 6 Departments of Medicine, Pathology, and Biochemistry and Molecular Biology, College of Medicine, Howard University, Washington, DC (H.A., H.B., Z.A.S.)
  • 7 Departments of Pediatrics and Medicine, Case Western Reserve University, Cleveland, Ohio (O.A., G.A.M., E.W.)
  • 8 Department of Emergency Medicine, School of Medicine, Stanford University, Stanford, California (A.L.B.)
  • 9 Department of Population Health, NYU Grossman School of Medicine, New York, New York (Y.C., A.B.T.)
  • 10 Department of Neurology, University of Utah, Salt Lake City, Utah (M.M.C.)
  • 11 Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama (N.B.E., P.G.)
  • 12 Massachusetts General Hospital, Biostatistics, Boston, Massachusetts (M.F., C.A.S.)
  • 13 Department of Pediatrics, University of California San Francisco, San Francisco, California (V.J.F.)
  • 14 Swedish Center for Research and Innovation, Providence Swedish Medical Center, and Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington (J.D.G.)
  • 15 Boston University Chobanian and Avedisian School of Medicine, Boston Medical Center, Boston, Massachusetts (N.M.H.)
  • 16 Division of Pulmonary and Critical Care, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia (J.E.H.)
  • 17 Institute for Systems Biology, Seattle, Washington (J.R.H.)
  • 18 Department of Obstetrics and Gynecology, University of California San Francisco, San Francisco, California (V.L.J.)
  • 19 Division of Pulmonary Sciences and Critical Care, Department of Internal Medicine, University of Colorado Anschutz Medical Campus, Denver, Colorado (S.E.J.)
  • 20 RECOVER Initiative, New York, New York (C.K., R.J.L., B.D.T.)
  • 21 Illinois Research Network (ILLInet) Hub and Department of Medicine, University of Illinois Chicago, Chicago, Illinois (J.A.K.)
  • 22 Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama (E.B.L.)
  • 23 Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, California (M.E.M.)
  • 24 Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah (T.D.M.)
  • 25 Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (J.M.Mullington)
  • 26 Division of Infectious Disease, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia (I.O., Z.W.)
  • 27 Departments of Pediatrics, Internal Medicine, and Health Policy, University of California San Francisco, San Francisco, California (M.J.O.)
  • 28 Division of Infectious Diseases, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas (C.C.P., T.F.P., B.S.T.)
  • 29 Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, California (M.J.P.)
  • 30 Division of Infectious Diseases, Department of Medicine, West Virginia University School of Medicine, Morgantown, West Virginia (R.R.)
  • 31 Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (H.N.S.)
  • 32 Department of Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa (U.S.)
  • 33 Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, Utah (J.D.T.)
  • 34 Department of Medicine, School of Medicine, and Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California (P.J.U.)
  • 35 Division of General Internal Medicine, Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska (A.J.V.)
  • 36 Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (J.P.W.)
  • 37 Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern Medicine, Chicago, Illinois (L.M.Y.)
  • 38 Department of Population Health and Department of Medicine, NYU Grossman School of Medicine, New York, New York (L.I.H.)
  • 39 Massachusetts General Hospital, Biostatistics, Harvard Medical School, and Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts (A.S.F.)
  • 40 Department of Medicine, WashU Medicine, St. Louis, Missouri (B.D.L.)
Ann Intern Med, 2026 Nov 03.
PMID: 42970801 DOI: 10.7326/ANNALS-25-05275

Abstract

BACKGROUND: Long COVID (LC) is widespread; however, limited information has been reported on the likelihood that symptoms remit over time.

OBJECTIVE: To evaluate the likelihood of improvement among persons with likely LC.

DESIGN: Prospective, multisite cohort study (RECOVER-Adult [Researching COVID to Enhance Recovery]).

SETTING: 83 U.S.-based sites across 33 states; Washington, DC; and Puerto Rico.

PARTICIPANTS: 1019 persons in RECOVER-Adult with likely LC (LC Research Index [LCRI] ≥11) 12 months after first SARS-CoV-2 infection.

MEASUREMENTS: The primary outcome was time until 2 consecutive study visits with LCRI less than 11. Secondary outcomes were time until LCRI measure reduced 50% or more and quality of life was good or better, and LCRI decreased to 0. Unadjusted estimates of cumulative incidence and adjusted marginal cumulative incidence by age, sex, SARS-CoV-2 wave, and LC subtype were reported across all follow-up time points.

RESULTS: An estimated 36.2% (95% CI, 33.0% to 39.5%) met the primary outcome by 24 months after infection, and 50.1% (CI, 46.1% to 54.0%) met the primary outcome by 36 months. An estimated 56.4% (CI, 52.2% to 60.4%) and 26.9% (CI, 23.3% to 30.5%), respectively, met the 2 secondary outcomes by 36 months. Among persons who still reported likely LC at 18 months and 24 months after first infection, relative timing of subsequent symptom improvement was similar.

LIMITATION: Findings in this observational cohort are interpretable in a population with prevalent likely LC and do not address causal relationships between individual characteristics and symptom improvement.

CONCLUSION: Among persons with likely LC 12 months after initial SARS-CoV-2 infection, one half experience meaningful reductions in symptoms by 36 months, whereas a quarter experience complete remission of symptoms. These findings underscore both the potential for natural recovery and the urgent need for placebo-controlled therapeutic intervention trials.

PRIMARY FUNDING SOURCE: National Institutes of Health.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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