Academic Journal
Is Cellular Senescence a Biological Feature of Long COVID? A Transcriptomic Analysis Across Comparative Postacute Sequelae Phenotypes.
| Τίτλος: | Is Cellular Senescence a Biological Feature of Long COVID? A Transcriptomic Analysis Across Comparative Postacute Sequelae Phenotypes. |
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| Συγγραφείς: | Epsi NJ; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Richard SA; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Morris MJ; Joint Base San Antonio-Fort Sam, Brooke Army Medical Center, Houston, Texas, USA., Lindholm DA; Joint Base San Antonio-Fort Sam, Brooke Army Medical Center, Houston, Texas, USA.; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Ganesan A; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; Division of Infectious Diseases, Walter Reed National Military Medical Center, Bethesda, Maryland, USA., Colombo RE; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.; Division of Infectious Diseases, Madigan Army Medical Center, Joint Base Lewis McChord, Fort Lewis, Washington, USA., Mende K; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; Joint Base San Antonio-Fort Sam, Brooke Army Medical Center, Houston, Texas, USA., Jones MU; Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Malloy AMW; Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Rubin LH; Department of Neurology, Psychiatry and Behavioral Sciences, Molecular and Cellular Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA., Agan BK; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Tribble DR; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Burgess TH; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA., Dalgard C; Department of Anatomy, Physiology and Genetics, Uniformed Services University, Bethesda, Maryland, USA., Puskarich MA; Department of Emergency Medicine, University of Minnesota, Minneapolis, Minnesota, USA., Pollett SD; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA. |
| Πηγή: | The Journal of infectious diseases [J Infect Dis] 2026 Oct 15; Vol. 234 (4), pp. e869-e880. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE |
| Imprint Name(s): | Publication: Jan. 2011- : Oxford : Oxford University Press Original Publication: 1904-2010 : Chicago, IL : University of Chicago Press |
| Ιατρικοί όροι (MeSH): | COVID-19*/genetics , COVID-19*/complications , COVID-19*/pathology , Cellular Senescence*/genetics, Humans ; Post-Acute COVID-19 Syndrome ; Phenotype ; Female ; Gene Expression Profiling ; Male ; Middle Aged ; SARS-CoV-2 ; Aged ; Transcriptome ; Cohort Studies ; Cognitive Dysfunction |
| Περίληψη: | Background: Cellular 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. Methods: Participants 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). Results: SenMayo 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. Conclusions: This study suggests a role of senescence-associated genes in the development of Long COVID, including shared and unique transcriptomic patterns across phenotypes. (© The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America.) |
| Competing Interests: | Potential conflicts of interest. S. D. P., T. H. B., and D. R. T. report that the Uniformed Services University (USU) Infectious Diseases Clinical Research Program (IDCRP), a US Department of War institution, and the Henry M. Jackson Foundation (HJF) were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of War Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both of these trials were part of the US Government COVID-19 response. Neither is related to the work presented here. |
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| Grant Information: | HU00012120103 National Institute of Allergy and Infectious Disease; Y1-AI-5072 United States NH NIH HHS; Department of War; Uniformed Services University of the Health Sciences; Y01 AI005072 United States AI NIAID NIH HHS; HU00012020067 Defense Health Program; Infectious Disease Clinical Research Program; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. |
| Contributed Indexing: | Keywords: COVID-19; SARS-CoV-2; SenMayo; cellular senescence; postacute sequelae |
| Entry Date(s): | Date Created: 20260624 Date Completed: 20261014 Latest Revision: 20261017 |
| Update Code: | 20261017 |
| PubMed Central ID: | PMC13668339 |
| DOI: | 10.1093/infdis/jiag315 |
| PMID: | 42340243 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1537-6613 |
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| DOI: | 10.1093/infdis/jiag315 |