Journal article
A multi-omics recovery factor predicts long COVID in the IMPACC study
The Journal of clinical investigation, v 135(21), Forthcoming
09 Sep 2025
PMID: 40924481
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Following SARS-CoV-2 infection, ~10-35% of COVID-19 patients experience long COVID (LC), in which debilitating symptoms persist for at least three months. Elucidating biologic underpinnings of LC could identify therapeutic opportunities.
We utilized machine learning methods on biologic analytes provided over 12-months after hospital discharge from >500 COVID-19 patients in the IMPACC cohort to identify a multi-omics "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 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.
LC participants had lower recovery factor scores compared to 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.
The multi-omics recovery factor identifies patients at risk of LC early after SARS-CoV-2 infection and reveals LC biomarkers and potential treatment targets.
gov NCT04378777.
This study was funded by NIH, NIAID and NSF.
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Details
- Title
- A multi-omics recovery factor predicts long COVID in the IMPACC study
- Creators
- Gisela Gabernet - Yale UniversityJessica Maciuch - Northwestern UniversityJeremy P Gygi - Yale UniversityJohn F Moore - The University of Texas at AustinAnnmarie Hoch - Boston Children's HospitalCaitlin Syphurs - Boston UniversityTianyi Chu - Yale School of MedicineNaresh Doni Jayavelu - University of WashingtonDavid B Corry - Baylor College of MedicineFarrah Kheradmand - Baylor College of MedicineLindsey R Baden - Brigham and Women's HospitalRafick-Pierre Sekaly - Case Western Reserve UniversityGrace A McComsey - University Hospitals of ClevelandElias K Haddad - Drexel UniversityCharles B Cairns - Drexel UniversityNadine Rouphael - Emory UniversityAna Fernandez-Sesma - Icahn School of Medicine at Mount SinaiViviana Simon - Icahn School of Medicine at Mount SinaiJordan P Metcalf - University of Oklahoma Health Sciences CenterNelson I Agudelo Higuita - OU HealthCatherine L Hough - Oregon Health & Science UniversityWilliam B Messer - Oregon Health & Science UniversityMark M Davis - Stanford UniversityKari C Nadeau - Stanford UniversityBali Pulendran - Palo Alto UniversityMonica Kraft - University of ArizonaChris Bime - University of ArizonaElaine F Reed - University of California, Los AngelesJoanna Schaenman - University of California, Los AngelesDavid J Erle - University of California, San FranciscoCarolyn S Calfee - University of California, San FranciscoMark A Atkinson - University of FloridaScott C Brakenridge - University of FloridaEsther Melamed - The University of Texas at AustinAlbert C Shaw - Yale UniversityDavid A Hafler - Yale UniversityAlison D Augustine - National Institute of Allergy and Infectious DiseasesPatrice M Becker - National Institute of Allergy and Infectious DiseasesAl Ozonoff - Boston Children's HospitalSteven E Bosinger - Emory UniversityWalter Eckalbar - University of California, San FranciscoHolden T Maecker - Stanford UniversitySeunghee Kim-Schulze - Icahn School of Medicine at Mount SinaiHanno Steen - Harvard UniversityFlorian Krammer - Icahn School of Medicine at Mount SinaiKerstin Westendorf - La Jolla Institute for ImmunologyImpacc Network - Cohort (United Kingdom)Bjoern Peters - La Jolla Institute for ImmunologySlim Fourati - Northwestern UniversityMatthew C Altman - Seattle UniversityOfer Levy - Boston Children's HospitalKinga K Smolen - Boston Children's HospitalRuth R Montgomery - Yale UniversityJoann Diray-Arce - Boston Children's HospitalSteven H Kleinstein - Yale UniversityLeying Guan - Yale UniversityLauren Ir Ehrlich - The University of Texas at Austin
- Publication Details
- The Journal of clinical investigation, v 135(21), Forthcoming
- Publisher
- American Society for Clinical Investigation
- Number of pages
- 17
- Grant note
- 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, 5T32DA018926-1, 3U19AI1289130, U19AI128913-04S1, R01AI122220 NIH: UM1TR004528 NSF: DMS2310836
This work is the result of NIH funding, in whole or in part, and is subject to the NIH Public Access Policy. Through acceptance of this federal funding, the NIH has been given a right to make the work publicly available in PubMed Central. center dot 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). center dot NIH (UM1TR004528). center dot NSF (DMS2310836).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Emergency Medicine
- Web of Science ID
- WOS:001650704800001
- Scopus ID
- 2-s2.0-105020798716
- Other Identifier
- 991022092353504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medicine, Research & Experimental