Evidence map›Paper›PMID 40321289›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Persistent immune dysregulation and metabolic alterations following SARS-CoV-2 infection.

Silvia Lucena Lage, Katherine Bricker-Holt, Joseph M Rocco, Adam Rupert, Frank X Donovan, Yevgeniya A Abramzon, Settara C Chandrasekharappa, Colton McNinch, Logan Cook, Eduardo Pinheiro Amaral and 10 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

20 authors.

Silvia Lucena LageDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, USA.
Katherine Bricker-HoltDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, USA.
Joseph M RoccoDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, USA.
Adam RupertAIDS Monitoring Laboratory, Frederick National Laboratory for Cancer Research; Frederick, USA.
Frank X DonovanCancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute; Bethesda, USA.
Yevgeniya A AbramzonCancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute; Bethesda, USA.
Settara C ChandrasekharappaCancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute; Bethesda, USA.
Colton McNinchBioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.
Logan CookDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, USA.
Eduardo Pinheiro AmaralInflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, USA.
Gabriel RosenfeldBioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA.
Thomas DalhuisenDepartment of Medicine, University of California, San Francisco; San Francisco, USA.
Avery EunDepartment of Medicine, University of California, San Francisco; San Francisco, USA.
Rebecca HohDepartment of Medicine, University of California, San Francisco; San Francisco, USA.
Emily FehrmanDepartment of Medicine, University of California, San Francisco; San Francisco, USA.
Jeffrey N MartinDepartment of Epidemiology and Biostatistics, University of California, San Francisco; San Francisco, USA.
Steven G DeeksDepartment of Medicine, University of California, San Francisco; San Francisco, USA.ORCID 0000-0001-6371-747X
Timothy J HenrichDepartment of Medicine, University of California, San Francisco; San Francisco, USA.
Michael J PelusoDepartment of Medicine, University of California, San Francisco; San Francisco, USA.
Irini SeretiDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SARS-CoV-2 can cause a variety of post-acute sequelae including Long COVID19 (LC), a complex, multisystem disease characterized by a broad range of symptoms including fatigue, cognitive impairment, and post-exertional malaise. The pathogenesis of LC is incompletely understood. In this study, we performed comprehensive cellular and transcriptional immunometabolic profiling within a cohort that included SARS-CoV-2-naïve controls (NC, N=30) and individuals with prior COVID-19 (~4-months) who fully recovered (RC, N=38) or went on to experience Long COVID symptoms (N=58). Compared to the naïve controls, those with prior COVID-19 demonstrated profound metabolic and immune alterations at the proteomic, cellular, and epigenetic level. Specifically, there was an enrichment in immature monocytes with sustained inflammasome activation and oxidative stress, elevated arachidonic acid levels, decreased tryptophan, and variation in the frequency and phenotype of peripheral T-cells. Those with LC had increased CD8 T-cell senescence and a distinct transcriptional profile within CD4 and CD8 T-cells and monocytes by single cell RNA sequencing. Our findings support a profound and persistent immunometabolic dysfunction that follows SARS-CoV-2 which may form the pathophysiologic substrate for LC. Our findings suggest that trials of therapeutics that help restore immune and metabolic homeostasis may be warranted to prevent, reduce, or resolve LC symptoms.

Indexed as

COVID-19immunosenescenceinflammationLong COVIDmetabolismpost-acute sequelae of SARS-CoV-2

Identifiers

PMID40321289
PMCPMC12047922

What OpenQuestion holds

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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.