Evidence mapPaperPMID 41559790Full record

ArticleJournal of translational medicine2026

Multilayer metabolomic integration reveals bioenergetic disruption in Long COVID.

María C García-Hidalgo, Natàlia Mota-Martorell, Jessica González, Iván D Benítez, Idoia Company-Marín, Mariona Jové, Ferran Barbé, Núria Amigó, Reinald Pamplona, David de Gonzalo-Calvo and 1 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

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

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
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

11 authors.

María C García-Hidalgo *Translational Research in Respiratory Medicine, Arnau de Vilanova and Santa Maria University Hospital, Avda. Alcalde Rovira Roure 80, Lleida, 25198, Spain.
Natàlia Mota-Martorell *Department of Experimental Medicine, University of Lleida (UdL), Lleida Biomedical Research Institute (IRBLleida), Lleida, Spain.
Jessica GonzálezTranslational Research in Respiratory Medicine, Arnau de Vilanova and Santa Maria University Hospital, Avda. Alcalde Rovira Roure 80, Lleida, 25198, Spain.
Iván D BenítezTranslational Research in Respiratory Medicine, Arnau de Vilanova and Santa Maria University Hospital, Avda. Alcalde Rovira Roure 80, Lleida, 25198, Spain.
Idoia Company-MarínDepartment of Experimental Medicine, University of Lleida (UdL), Lleida Biomedical Research Institute (IRBLleida), Lleida, Spain.
Mariona JovéDepartment of Experimental Medicine, University of Lleida (UdL), Lleida Biomedical Research Institute (IRBLleida), Lleida, Spain.
Ferran BarbéTranslational Research in Respiratory Medicine, Arnau de Vilanova and Santa Maria University Hospital, Avda. Alcalde Rovira Roure 80, Lleida, 25198, Spain.
Núria AmigóBiosfer Teslab, Reus, Spain.
Reinald PamplonaDepartment of Experimental Medicine, University of Lleida (UdL), Lleida Biomedical Research Institute (IRBLleida), Lleida, Spain.
David de Gonzalo-Calvo *Translational Research in Respiratory Medicine, Arnau de Vilanova and Santa Maria University Hospital, Avda. Alcalde Rovira Roure 80, Lleida, 25198, Spain. dgonzalo@irblleida.cat.ORCID http://orcid.org/0000-0003-2240-3532
Gerard Torres *Translational Research in Respiratory Medicine, Arnau de Vilanova and Santa Maria University Hospital, Avda. Alcalde Rovira Roure 80, Lleida, 25198, Spain. gtorres@gss.cat.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLong COVID represents a significant health challenge, with 10–20% of patients with COVID-19 experiencing persistent multiorgan symptoms. The heterogeneity of clinical manifestations, combined with an incomplete understanding of the underlying molecular mechanisms, limits the improvement of patient management. Circulating metabolomic profiling constitutes a promising tool to address these limitations. In this context, we aim to investigate long-term metabolic disruptions in Long COVID through multilayer integration of plasma metabolites.

methodsThe study population included 42 survivors of critical COVID-19 who attended a comprehensive clinical evaluation conducted 12 months postdischarge. Plasma biochemicals, including lipoproteins, lipids, glycoproteins and metabolites were quantified using proton nuclear magnetic resonance spectroscopy (H-NMR). Circulating tricarboxylic acid (TCA) cycle intermediates and protein damage markers were detected by gas chromatography‒mass spectrometry (GC/MS). A machine learning-based feature selection approach was employed to identify the multilayered metabolic signature. Generalized additive models (GAMs) were used to explore associations between individual metabolites and specific dimensions of Long COVID.

resultsUnivariate analysis revealed significantly elevated levels of alpha-ketoglutarate (aKG) and reduced levels of creatine in patients with Long COVID. A nine-metabolite and damage marker signature [aKG, carboxymethyl-cysteine (CMC), carboxymethyl-lysine (CML), creatine, fumarate, lactate, low density lipoprotein particle size (LDL-Z), 2-succinyl-cysteine (2SC) and tyrosine] was identified through the integration of Random Forest with Boruta and Sparse Partial Least Squares regression. This signature effectively classified patients with Long COVID (a cross-validated AUC of 0.91). In the GAM models, aKG, CMC, CML and creatine were associated with distinct Long COVID dimensions, including cognitive, functional and respiratory impairments.

conclusionsMultilayer metabolomic integration reveals persistent bioenergetic disruption in patients with Long COVID. The identified metabolic profile offers promising biomarkers for medical decision-making. Modulating key metabolites could potentially mitigate specific symptoms of long COVID.

Indexed as

COVID-19Energy MetabolismMetabolomeMetabolomicsAgedBiomarkersFemaleGas Chromatography-Mass SpectrometryHumansKetoglutaric AcidsMaleMiddle AgedPost-Acute COVID-19 SyndromeSARS-CoV-2BiomarkersKetoglutaric AcidsBiomarkersLong COVIDMetabolomicsMitochondriaMultilayer integration

Identifiers

PMID41559790
PMCPMC12903254

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.