Evidence map›Paper›PMID 41212055›Full record

ArticleJCI insight2025

Minimalistic transcriptomic signatures permit accurate early prediction of COVID-19 mortality.

Rithwik Narendra, Emily C Lydon, Hoang Van Phan, Natasha Spottiswoode, Lucile P Neyton, Joann Diray-Arce, IMPACC Network, COMET Consortium, EARLI Consortium, Patrice M Becker and 31 more

Abstract readMulticenter Study
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Reply to Liu et al. and Chen et al.American journal of respiratory and critical care medicine · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

41 authors.

Rithwik NarendraUCSF, San Francisco, California, USA.
Emily C LydonUCSF, San Francisco, California, USA.
Hoang Van PhanUCSF, San Francisco, California, USA.
Natasha SpottiswoodeUCSF, San Francisco, California, USA.
Lucile P NeytonUCSF, San Francisco, California, USA.
Joann Diray-ArcePrecision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
IMPACC Network
COMET Consortium
EARLI Consortium
Patrice M BeckerNational Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Seunghee Kim-SchulzeIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Annmarie HochPrecision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Harry PickeringUCLA, Los Angeles, California, USA.
Patrick van ZalmPrecision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Charles B CairnsDrexel University, Tower Health Hospital, Philadelphia, Pennsylvania, USA.
Matthew C AltmanBenaroya Research Institute, University of Washington, Seattle, Washington, USA.
Alison D AugustineNational Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Steve BosingerEmory School of Medicine, Atlanta, Georgia, USA.
Walter EckalbarUCSF, San Francisco, California, USA.
Leying GuanYale School of Public Health, New Haven, Connecticut, USA.
Naresh Doni JayaveluBenaroya Research Institute, University of Washington, Seattle, Washington, USA.
Steven H KleinsteinYale School of Medicine, New Haven, Connecticut, USA.
Florian KrammerIcahn School of Medicine at Mount Sinai, New York, New York, USA.
Holden T MaeckerStanford University School of Medicine, Palo Alto, California, USA.
Al OzonoffPrecision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Bjoern PetersLa Jolla Institute for Immunology, La Jolla, California, USA.
Nadine RouphaelEmory School of Medicine, Atlanta, Georgia, USA.
Ruth R MontgomeryYale School of Medicine, New Haven, Connecticut, USA.
Elaine ReedUCLA, Los Angeles, California, USA.
Joanna SchaenmanUCLA, Los Angeles, California, USA.
Hanno SteenPrecision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ofer LevyPrecision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sidney C HallerUCSF, San Francisco, California, USA.
David ErleUCSF, San Francisco, California, USA.
Carolyn M HendricksonUCSF, San Francisco, California, USA.
Matthew F KrummelUCSF, San Francisco, California, USA.
Michael A MatthayUCSF, San Francisco, California, USA.
Prescott WoodruffUCSF, San Francisco, California, USA.
Elias K HaddadDrexel University, Tower Health Hospital, Philadelphia, Pennsylvania, USA.
Carolyn S CalfeeUCSF, San Francisco, California, USA.
Charles R LangelierUCSF, San Francisco, California, 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
Translation of immunologic technologies from basic research into pre-clinical nonU19AI062629 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI FARRIS, A DARISE · 2004 to 2023
$56.2M
Systems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI Steven H. Kleinstein · 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 MERAD, MIRIAM · 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
Transcriptomics to define biomarkers of neonatal vaccine immunogenicityU19AI118608 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LEVY, OFER · 2017 to 2021
$24.7M
Tollip inhibits IL-33 signaling during airway influenza virus infectionU19AI125357 · NIAID · UNIVERSITY OF ARIZONA · PI KRAFT, MONICA · 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
Project 3: Mapping the Evolution of Chronic Transplant Injury in the Context of CMV InfectionU19AI128913 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REED, ELAINE F, SARWAL, MINNIE M · 2017 to 2021
$11.2M
The contribution of GPCRs to thymocyte medullary entry and central toleranceR01AI104870 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI Lauren Ilyse Richie EHRLICH · 2014 to 2026
$7.6M
Investigating the impact of helminth infection on microbioma composition and innate immunity generated during HepB vaccination. U19AI128910 · NIAID · DREXEL UNIVERSITY · PI HADDAD, ELIAS K · 2017 to 2021
$7.0M
NHLBI NIH HHS R35 HL140026NIAID NIH HHS R01 AI104870NIAID NIH HHS R01 AI132774NIAID NIH HHS R01 AI135803NIAID NIH HHS R01 AI145835NIAID NIH HHS T32 AI007641NIAID 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 U54 AI142766
6 · The paper itself

Abstract

BACKGROUNDAccurate prognostic assays for COVID-19 represent an unmet clinical need. We sought to identify and validate early parsimonious transcriptomic signatures that accurately predict fatal outcomes.METHODSWe studied 894 patients enrolled in the prospective, multicenter Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) with peripheral blood mononuclear cells (PBMC) and nasal swabs collected within 48 hours of admission. Host gene expression was measured with RNA-Seq. We trained parsimonious prognostic classifiers incorporating host gene expression, age, and SARS-CoV-2 viral load to predict 28-day mortality in 70% of the cohort. Classifier performance was determined in the remaining 30% and externally validated in a contemporary COVID-19 cohort (n = 137) with vaccinated patients.RESULTSFatal COVID-19 was characterized by 4,189 differentially expressed genes in the peripheral blood. A COVID-specific 3-gene peripheral blood classifier (CD83, ATP1B2, DAAM2) combined with age and SARS-CoV-2 viral load achieved an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI, 0.82-0.94). A 3-gene nasal classifier (SLC5A5, CD200R1, FCER1A), in comparison, yielded an AUC of 0.74 (95% CI, 0.64-0.83). Notably, OLAH, the most strongly upregulated gene in both PBMC and nasal swab and recently implicated in severe viral infection pathogenesis, yielded AUCs of 0.86 (0.79-0.93) and 0.78 (95% CI, 0.69-0.86), respectively. Both peripheral blood classifiers demonstrated comparable performance in an independent contemporary cohort of vaccinated patients (AUCs 0.74-0.80).CONCLUSIONOur parsimonious blood- and nasal-based classifiers accurately predicted COVID-19 mortality and merit further study as accessible prognostic tools to guide triage, resource allocation, and early therapeutic interventions.FUNDINGNIH: 5R01AI135803-03, R35HL140026, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, 5T32DA018926-18, and K0826161611. National Institute of Allergy and Infectious Diseases, NIH: 3U19AI1289130, U19AI128913-04S1, and R01AI122220. National Center for Advancing Translational Sciences, NIH: UM1TR004528. The National Science Foundation: DMS2310836. The Chan Zuckerberg Biohub San Francisco.

Indexed as

COVID-19TranscriptomeAdultAgedFemaleGene Expression ProfilingHumansLeukocytes, MononuclearMaleMiddle AgedPrognosisProspective StudiesSARS-CoV-2Viral LoadBiomarkersCOVID-19Infectious diseaseMachine learningPulmonology

Identifiers

PMID41212055
PMCPMC12643502

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.