Evidence map›Paper›PMID 42340243›Full record

ArticleThe Journal of infectious diseases2026

Is Cellular Senescence a Biological Feature of Long COVID? A Transcriptomic Analysis Across Comparative Postacute Sequelae Phenotypes.

Nusrat J Epsi, Stephanie A Richard, Michael J Morris, David A Lindholm, Anuradha Ganesan, Rhonda E Colombo, Katrin Mende, Milissa U Jones, Allison M W Malloy, Leah H Rubin and 6 more

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In one paragraph

Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 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
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
Michael J MorrisJoint Base San Antonio-Fort Sam, Brooke Army Medical Center, Houston, Texas, USA.ORCID 0000-0003-4903-4343
David A LindholmJoint Base San Antonio-Fort Sam, Brooke Army Medical Center, Houston, Texas, USA.ORCID 0000-0001-5428-7404
Anuradha GanesanInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Rhonda E ColomboInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.ORCID 0000-0003-0154-1928
Katrin MendeInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Milissa U JonesDepartment of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Allison M W MalloyDepartment of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.ORCID 0000-0003-2962-0302
Leah H RubinDepartment of Neurology, Psychiatry and Behavioral Sciences, Molecular and Cellular Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, 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
David R TribbleInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Timothy H BurgessInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.ORCID 0000-0003-1247-8370
Clifton DalgardDepartment of Anatomy, Physiology and Genetics, Uniformed Services University, Bethesda, Maryland, USA.ORCID 0000-0003-2025-8239
Michael A PuskarichDepartment of Emergency Medicine, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0001-6358-4670
Simon D PollettInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Funding

Defense Health Program HU00012020067Department of WarHenry M. Jackson Foundation for the Advancement of Military Medicine, Inc.Infectious Disease Clinical Research ProgramNational Institute of Allergy and Infectious Disease HU00012120103NIAID NIH HHS Y01 AI005072NIH HHS Y1-AI-5072Uniformed Services University of the Health Sciences
6 · The paper itself

Abstract

backgroundCellular senescence, involving cell-cycle arrest and inflammatory factor release, may play a role in Long COVID development. We investigated the role of senescence-associated genes across multiple postacute sequelae phenotypes.

methodsParticipants from a cohort study were grouped into post-COVID-19 groups: (1) sensory, fatigue/difficulty thinking, and difficulty breathing/exercise intolerance, identified through a machine learning analysis of symptom data; (2) cognitive impairment, measured using a screening cognitive assessment tool (BRACE); and (3) persistent dyspnea, identified using a symptom-scale known to correlate with a 6-minute-walk-test. Postinfection whole-blood samples underwent transcriptomic analysis with 47 125 genes used as the reference signature for gene set enrichment analysis against the SenMayo cellular-senescence query gene set (n = 125); enrichment were based on normalized enrichment scores (NES).

resultsSenMayo genes were significantly upregulated in the early postinfection period in (1) 56 individuals who subsequently developed Long COVID symptom phenotypes, compared to 104 who did not develop Long COVID symptoms (NES = 6.04, P = .001); (2) 32 individuals with long-term cognitive impairment compared with 40 without long-term cognitive impairment measured by BRACE (NES = 2.58, P = .032); and (3) 26 participants who had persistent dyspnea compared with 53 without persistent dyspnea measured by the validated dyspnea instrument (NES = 6.29, P = .001). ETS2 was upregulated across all impairment-related phenotypes, while other SenMayo genes showed phenotype-specific variability.

conclusionsThis study suggests a role of senescence-associated genes in the development of Long COVID, including shared and unique transcriptomic patterns across phenotypes.

Indexed as

Cellular SenescenceCOVID-19AgedCognitive DysfunctionCohort StudiesFemaleGene Expression ProfilingHumansMaleMiddle AgedPhenotypePost-Acute COVID-19 SyndromeSARS-CoV-2Transcriptomecellular senescenceCOVID-19postacute sequelaeSARS-CoV-2SenMayo

Identifiers

PMID42340243
PMCPMC13668339

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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.