Evidence map›Paper›PMID 40924481›Full record

ArticleThe Journal of clinical investigation2025

A multiomics recovery factor predicts long COVID in the IMPACC study.

Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand and 47 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04378777 (A Prospective Cohort Study to Assess Longitudinal Immune Responses in Hospitalized Patients With COVID-19), which is not on this map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04378777 completednot on this map

A Prospective Cohort Study to Assess Longitudinal Immune Responses in Hospitalized Patients With COVID-19 (DAIT-COVID-19-002)

TypeobservationalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2020 to 2022Enrolled1,227ConditionsCoronavirus Disease 2019 (COVID-19), SARS-CoV-2ArmsBiological sample collection, Data Collection: Clinical Care Assessments
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. VSL#3British journal of biomedical science · 2026
    Trial
  3. Review
  4. Persistent CD4Cellular immunology · 2026
    Article
  5. Review
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

57 authors.

Gisela GabernetYale School of Medicine, New Haven, Connecticut, USA.
Jessica MaciuchNorthwestern Feinberg School of Medicine, Chicago, Illinois, USA.
Jeremy P GygiYale School of Medicine, New Haven, Connecticut, USA.
John F MooreThe University of Texas at Austin, Austin, Texas, USA.
Annmarie HochClinical and Data Coordinating Center (CDCC), Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Caitlin SyphursClinical and Data Coordinating Center (CDCC), Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tianyi ChuYale School of Medicine, New Haven, Connecticut, USA.
Naresh Doni JayaveluBenaroya Research Institute, University of Washington, Seattle, Washington, USA.
David B CorryBaylor College of Medicine and the Center for Translational Research on Inflammatory Diseases, Houston, Texas, USA.
Farrah KheradmandBaylor College of Medicine and the Center for Translational Research on Inflammatory Diseases, Houston, Texas, USA.
Lindsey R BadenBrigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Rafick-Pierre SekalyCase Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
Grace A McComseyCase Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
Elias K HaddadDrexel University, Tower Health Hospital, Philadelphia, Pennsylvania, USA.
Charles B CairnsDrexel University, Tower Health Hospital, Philadelphia, Pennsylvania, USA.
Nadine RouphaelEmory School of Medicine, Atlanta, Georgia, USA.
Ana Fernandez-SesmaIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Viviana SimonIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Jordan P MetcalfOklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA.
Nelson I Agudelo HiguitaOklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA.
Catherine L HoughOregon Healthand Science University, Portland, Oregon, USA.
William B MesserOregon Healthand Science University, Portland, Oregon, USA.
Mark M DavisStanford University School of Medicine, Palo Alto, California, USA.
Kari C NadeauStanford University School of Medicine, Palo Alto, California, USA.
Bali PulendranStanford University School of Medicine, Palo Alto, California, USA.
Monica KraftUniversity of Arizona, Tucson, Arizona, USA.
Chris BimeUniversity of Arizona, Tucson, Arizona, USA.
Elaine F ReedDavid Geffen School of Medicine at the UCLA, Los Angeles California, USA.
Joanna SchaenmanDavid Geffen School of Medicine at the UCLA, Los Angeles California, USA.
David J ErleUCSF, San Francisco, California, USA.
Carolyn S CalfeeUCSF, San Francisco, California, USA.
Mark A AtkinsonUniversity of Florida, Gainesville, Florida, USA.
Scott C BrakenridgeUniversity of Florida, Gainesville, Florida, USA.
Esther MelamedThe University of Texas at Austin, Austin, Texas, USA.
Albert C ShawYale School of Medicine, New Haven, Connecticut, USA.
David A HaflerYale School of Medicine, New Haven, Connecticut, USA.
Alison D AugustineNational Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
Patrice M BeckerNational Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
Al OzonoffClinical and Data Coordinating Center (CDCC), Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Steven E BosingerEmory School of Medicine, Atlanta, Georgia, USA.
Walter EckalbarUCSF, San Francisco, California, USA.
Holden T MaeckerStanford University School of Medicine, Palo Alto, California, USA.
Seunghee Kim-SchulzeIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Hanno SteenPrecision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Maryland, USA.
Florian KrammerIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Kerstin WestendorfLa Jolla Institute for Immunology, La Jolla, California, USA.
IMPACC Network
Bjoern PetersLa Jolla Institute for Immunology, La Jolla, California, USA.
Slim FouratiNorthwestern Feinberg School of Medicine, Chicago, Illinois, USA.
Matthew C AltmanBenaroya Research Institute, University of Washington, Seattle, Washington, USA.
Ofer LevyPrecision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Maryland, USA.
Kinga K SmolenPrecision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Maryland, USA.
Ruth R MontgomeryYale School of Medicine, New Haven, Connecticut, USA.
Joann Diray-ArceClinical and Data Coordinating Center (CDCC), Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Steven H KleinsteinYale School of Medicine, New Haven, Connecticut, USA.
Leying GuanYale School of Medicine, New Haven, Connecticut, USA.
Lauren Ir EhrlichThe University of Texas at Austin, Austin, Texas, USA.

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
Translation of immunologic technologies from basic research into pre-clinical nonU19AI062629 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI COGGESHALL, KENNETH MARK · 2004 to 2023
$56.2M
Systems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI Albert C Shaw · 2010 to 2026
$50.4M
Project 3 - Ex vivo immune profiling of dengue viruses and vaccinesU19AI118610 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HARRIS, EVA · 2015 to 2021
$46.6M
Systems Biological Analysis of Innate and Adaptive Responses to VaccinationU19AI090023 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI, LI, SHUZHAO · 2010 to 2021
$45.0M
Understanding Asthma EndotypesU19AI077439 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PRESCOTT G WOODRUFF · 2008 to 2026
$41.1M
Clinical and Translational Science Collaborative of Northern Ohio, Catalyzing Linkages to Equity in Health (CLE Health)UM1TR004528 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI GRACE A MCCOMSEY · 2023 to 2026
$32.1M
Transcriptomics to define biomarkers of neonatal vaccine immunogenicityU19AI118608 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2017 to 2021
$24.7M
HIPC Data Coordinating CenterU01AI167892 · NIAID · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI Steven H. Kleinstein, Bjoern Peters · 2022 to 2026
$18.7M
Tollip inhibits IL-33 signaling during airway influenza virus infectionU19AI125357 · NIAID · UNIVERSITY OF ARIZONA · PI KRAFT, MONICA, VERCELLI, DONATA · 2016 to 2025
$14.7M
Systems Immunology profiling of respiratory viral infections in vulnerable populationsU19AI167891 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI Erik Wambre · 2022 to 2026
$14.0M
NCATS NIH HHS UL1 TR002369NCATS NIH HHS UM1 TR004528NIAID NIH HHS R01 AI104870NIAID NIH HHS R01 AI122220NIAID NIH HHS R01 AI132774NIAID NIH HHS R01 AI135803NIAID NIH HHS R01 AI145835NIAID NIH HHS U01 AI167892NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI062629NIAID NIH HHS U19 AI077439NIAID NIH HHS U19 AI089992NIAID NIH HHS U19 AI090023NIAID NIH HHS U19 AI118608NIAID NIH HHS U19 AI118610NIAID NIH HHS U19 AI125357NIAID NIH HHS U19 AI128910NIAID NIH HHS U19 AI128913NIAID NIH HHS U19 AI167891NIAID NIH HHS U19 AI167903NIAID NIH HHS U54 AI142766NIDA NIH HHS T32 DA018926
6 · The paper itself

Abstract

BACKGROUNDFollowing SARS-CoV-2 infection, approximately 10%-35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.METHODSWe utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics "recovery factor," trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor scores were tested for association with LC, disease severity, clinical parameters, and immune subset frequencies. Enrichment analyses identified biologic pathways associated with recovery factor scores.RESULTSParticipants with LC had lower recovery factor scores compared with recovered participants. Recovery factor scores predicted LC as early as hospital admission, irrespective of acute COVID-19 severity. Biologic characterization revealed increased inflammatory mediators, elevated signatures of heme metabolism, and decreased androgenic steroids as predictive and ongoing biomarkers of LC. Lower recovery factor scores were associated with reduced lymphocyte and increased myeloid cell frequencies. The observed signatures are consistent with persistent inflammation driving anemia and stress erythropoiesis as major biologic underpinnings of LC.CONCLUSIONThe multiomics recovery factor identifies patients at risk of LC early after SARS-CoV-2 infection and reveals LC biomarkers and potential treatment targets.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID), NIH (3U01AI167892-03S2, 3U01AI167892-01S2, 5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI057229-18, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07S1, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-1, 3U19AI1289130, U19AI128913-04S1, R01AI122220); NIH (UM1TR004528); and National Science Foundation (NSF) (DMS2310836).

Indexed as

COVID-19SARS-CoV-2AdultAgedFemaleHumansMachine LearningMaleMetabolomicsMiddle AgedMultiomicsBiomarkersCOVID-19ImmunologyInfectious diseaseMachine learning

Identifiers

PMID40924481
PMCPMC12582403

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.