Evidence map›Paper›PMID 38916431›Full record

ArticleThe Journal of infectious diseases2025

Precision Symptom Phenotyping Identifies Early Clinical and Proteomic Predictors of Distinct COVID-19 Sequelae.

Nusrat J Epsi, Josh G Chenoweth, Paul W Blair, David A Lindholm, Anuradha Ganesan, Tahaniyat Lalani, Alfred Smith, Rupal M Mody, Milissa U Jones, Rhonda E Colombo and 26 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing 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.

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

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

  1. Pooled it
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

36 authors.

Nusrat J EpsiInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.ORCID 0000-0001-5363-075X
Josh G ChenowethHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
Paul W BlairHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
David A LindholmDivision of Infectious Diseases, Brooke Army Medical Center, San Antonio, Texas, USA.
Anuradha GanesanInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Tahaniyat LalaniInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.ORCID 0000-0002-9361-2991
Alfred SmithDivision of Infectious Diseases, Naval Medical Center Portsmouth, Portsmouth, Virginia, USA.
Rupal M ModyDivision of Infectious Diseases, William Beaumont Army Medical Center, El Paso, Texas, USA.
Milissa U JonesDivision of Infectious Diseases, Tripler Army Medical Center, Honolulu, Hawaii, USA.
Rhonda E ColomboInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Christopher J ColomboDivision of Infectious Diseases, Madigan Army Medical Center, Tacoma, Washington, USA.ORCID 0000-0001-5499-3368
Christina SchofieldDivision of Infectious Diseases, Madigan Army Medical Center, Tacoma, Washington, USA.
Evan C EwersDepartment of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Derek T LarsonDepartment of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Catherine M BerjohnInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Ryan C MavesInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Anthony C FriesThe Applied Technology and Genomics (PHT) Division, U.S. Air Force School of Aerospace Medicine, Dayton, Ohio, USA.
David ChangDepartment of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Andrew WyattDivision of Infectious Diseases, Landstuhl Regional Medical Center, Landstuhl, Germany.
Ann I ScherDepartment of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Celia ByrneDepartment of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Jennifer RusieckiDepartment of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
David L SaundersDepartment of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Jeffrey LivezeyDepartment of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Allison MalloyDepartment of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Samantha BazanDepartment of Primary Care, Carl R. Darnall Army Medical Center, Fort Cavazos, Texas, USA.
Carlos MaldonadoDepartment of Clinical Investigation, Womack Army Medical Center, Fort Liberty, North Carolina, USA.
Margaret Sanchez EdwardsInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Katrin MendeInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Mark P SimonsInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Robert J O'ConnellInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
David R TribbleInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Brian K AganInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.ORCID 0000-0002-5114-1669
Timothy H BurgessInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Simon D PollettInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Stephanie A RichardInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.ORCID 0000-0002-0530-384X

Funding

Defense Health Program HU00012020067Department of DefenseInfectious Disease Clinical Research ProgramNational Institute of Allergy and Infectious Diseases HU00011920111National Institute of Allergy and Infectious Diseases HU00012020070NIAID NIH HHS Y01 AI005072NIH HHS Y1-AI-5072Uniformed Services University of the Health Sciences
6 · The paper itself

Abstract

backgroundPost-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints.

methodsThis analysis included 1988 SARS-CoV-2 positive U.S. Military Health System beneficiaries who had quantitative post-COVID symptom scores. Among participants who reported moderate-to-severe symptoms on surveys collected 6 months post-SARS-CoV-2 infection, principal component analysis followed by k-means clustering identified distinct clusters of symptoms.

resultsThree symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization than those with no/mild symptoms at 6 months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking and elevated ICAM-1 concentrations to sensory symptoms.

conclusionsWe identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC.

Indexed as

COVID-19AdultFatigueFemaleFibrin Fibrinogen Degradation ProductsHumansInterleukin 1 Receptor Antagonist ProteinMaleMiddle AgedPhenotypePost-Acute COVID-19 SyndromeProteomicsSARS-CoV-2Severity of Illness IndexFibrin Fibrinogen Degradation Productsfibrin fragment DInterleukin 1 Receptor Antagonist ProteinCOVID-19 symptomslong COVIDmachine learningpost-COVID conditionsSARS-CoV-2

Identifiers

PMID38916431
PMCPMC12308661

What OpenQuestion holds

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LicenceCC BY-NC-ND
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 OpenQuestion graph.