# Assessment of physical status and analysis of lipidomic and metabolomic alterations in patients with Post-COVID-19 condition

**Authors:** Raúl Pavón, Sandra Parra, Francisco Javier Rubio, Mireia Feliu, Marta Ríos, Simona Iftimie, Conxita Rovira, Nuria Amigó, Lydia Cabau, Neus Martínez-Micaelo, Antoni Castro, Anil Bhatia, Anil Bhatia, Anil Bhatia

PMC · DOI: 10.1371/journal.pone.0341192 · PLOS One · 2026-03-03

## TL;DR

This study explores physical and metabolic changes in long COVID patients, finding muscle weakness and altered lipid and metabolite levels that may explain ongoing symptoms.

## Contribution

The study provides novel insights into the lipidomic and metabolomic profiles of Post-COVID-19 patients, linking these changes to persistent symptoms.

## Key findings

- PCC patients showed reduced muscle strength and exercise tolerance, likely due to peripheral muscle involvement.
- PCC patients had lower HDL-cholesterol and altered glucose/lactate levels, suggesting mitochondrial dysfunction.
- Elevated glycine and reduced glutamate levels in PCC patients may relate to neurological symptoms and metabolic stress.

## Abstract

The development and persistence of symptoms following SARS-CoV-2 infection, known as Post-COVID-19 Condition (PCC) or “long COVID,” represents a global health challenge. In this prospective cross-sectional study, we conducted a detailed assessment of the physical condition of 46 patients using handgrip dynamometry, ergoespirometry, and the 6-minute walk test (6MWT). The results revealed a loss of muscle strength and poor exercise tolerance primarily due to peripheral muscle involvement. To complement and better understand these findings, we compared the blood metabolome and lipidome of 13 patients with PCC, 13 patients with acute COVID-19 infection, and 13 healthy controls using magnetic resonance spectroscopy (1H-NMR). PCC patients showed lower levels of HDL-cholesterol, as well as medium and dense HDL particles, which could contribute to a pro-atherogenic and pro-inflammatory state. Although no significant differences were observed in glycoproteins, we found decreased glucose and increased lactate levels, supporting the hypothesis of mitochondrial dysfunction in PCC patients. Additionally, elevated glycine and reduced glutamate levels may be related to the neurological symptoms associated with the condition. We also observed increased levels of glutamine, leucine, and isoleucine, indicating protein hypercatabolism and metabolic stress. These findings suggest that alterations in the metabolome and lipidome of PCC patients may be contributing to the persistence of their symptoms.

## Linked entities

- **Chemicals:** glucose (PubChem CID 5793), lactate (PubChem CID 61503), glycine (PubChem CID 750), glutamate (PubChem CID 611), glutamine (PubChem CID 738), leucine (PubChem CID 857), isoleucine (PubChem CID 791)

## Full-text entities

- **Genes:** SHROOM4 (shroom family member 4) [NCBI Gene 57477] {aka MRXSSDS, SHAP, shrm4}
- **Diseases:** diabetes (MESH:D003920), neuropsychiatric disorders (MESH:D001523), Alzheimer diseases (MESH:D000544), neurotoxicity (MESH:D020258), dyspnea (MESH:D004417), abdominal pain (MESH:D015746), critically ill (MESH:D016638), muscle involvement (MESH:C566343), neurodegenerative diseases (MESH:D019636), inflammation (MESH:D007249), sarcopenia (MESH:D055948), headaches (MESH:D006261), muscle strength (MESH:D019042), mitochondrial dysfunction (MESH:D028361), respiratory disease (MESH:D012140), atherogenic dyslipidemia (MESH:D050171), ARDS (MESH:D012128), acute infection (MESH:D000208), neurological symptoms (MESH:D009461), autoimmune and inflammatory diseases (MESH:D001327), obesity (MESH:D009765), respiratory failure (MESH:D012131), CCC (MESH:C535313), overweight (MESH:D050177), fatigue (MESH:D005221), Coronavirus Disease 2019 (MESH:D000086382), post (MESH:D000094025), gastrointestinal, cardiovascular, neuropsychiatric, or musculoskeletal (MESH:D005767), cardiovascular disease (MESH:D002318), neurocognitive impairments (MESH:D019965), infection (MESH:D007239), cough (MESH:D003371), arthralgia (MESH:D018771), non-ketotic hyperglycinemia (MESH:D020158), respiratory symptoms (MESH:D012818), viral infections (MESH:D014777), atherogenesis (MESH:D050197), Hypertension (MESH:D006973), hyperglycinemic encephalopathy (MESH:D001927), oncological disease (MESH:D000072716), PCC (MESH:D000094024), infectious disease (MESH:D003141), fog (MESH:D005222), depressive disorder (MESH:D003866), T2D (MESH:D003924), myalgia (MESH:D063806), Parkinson (MESH:D010302), loss of muscle strength (MESH:D009135)
- **Chemicals:** isoleucine (MESH:D007532), lactate (MESH:D019344), omega-3 fatty acids (MESH:D015525), triglycerides (MESH:D014280), oxygen (MESH:D010100), sugar (MESH:D000073893), phosphate (MESH:D010710), glutamate (MESH:D018698), BCAAs (MESH:D000597), Glycine (MESH:D005998), cholesterol (MESH:D002784), ketone bodies (MESH:D007657), D2O (MESH:D017666), leucine (MESH:D007930), amino acid (MESH:D000596), carbohydrate (MESH:D002241), sphingomyelin (MESH:D013109), 1H (-), sphingolipids (MESH:D013107), glucose (MESH:D005947), steroids (MESH:D013256), glutamine (MESH:D005973), Lipid (MESH:D008055)
- **Species:** Nicotiana tabacum (American tobacco, species) [taxon 4097], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12956072/full.md

## References

51 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956072/full.md

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Source: https://tomesphere.com/paper/PMC12956072