Evidence map›Paper›PMID 40649860›Full record

ArticleInternational journal of molecular sciences2025

Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID.

Gong-Hua Li, Fei-Fei Han, Efthymios Kalafatis, Qing-Peng Kong, Wenzhong Xiao

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
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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

5 authors.

Gong-Hua LiState Key Laboratory of Genetic Evolution and Animal Models, Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China.ORCID 0000-0002-9311-6613
Fei-Fei HanComputational Research Center for Complex Chronic Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Efthymios KalafatisIndependent Researcher, 185 37 Pireas, Greece.ORCID 0009-0007-9228-7780
Qing-Peng KongState Key Laboratory of Genetic Evolution and Animal Models, Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China.ORCID 0000-0002-6046-4494
Wenzhong XiaoComputational Research Center for Complex Chronic Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0003-4944-6380

Funding

Open Medicine Foundation Research Fund
6 · The paper itself

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID are complex multisystem conditions that pose significant challenges in healthcare. Accumulated research evidence suggests that ME/CFS and Long COVID exhibit overlapping metabolic symptoms, indicating potential shared metabolic dysfunctions. This study aims to systematically explore shared metabolic disturbances in the muscle tissue of patients. Utilizing genome-wide metabolic modeling, we identified key metabolic irregularities in the muscle of patients with ME/CFS, notably the downregulation of the alanine and aspartate metabolism pathway and the arginine and proline metabolism pathway. Further, in silico knockout analyses suggested that supplementation with aspartate (ASP) or asparagine (ASN) could potentially ameliorate these metabolic deficiencies. In addition, assessments of metabolomic levels in Long COVID patients also showed the significant downregulation of ASP during post-exertional malaise (PEM) in both muscle and blood. Consequently, we propose that a combination of l-ornithine and l-aspartate (LOLA) is a potential candidate to alleviate metabolic symptoms in ME/CFS and Long COVID for future clinical trials.

Indexed as

COVID-19Fatigue Syndrome, ChronicAdultAlanineAsparagineAspartic AcidFemaleHumansMaleMetabolic Networks and PathwaysMetabolomeMetabolomicsProlineSARS-CoV-2AlanineAsparagineAspartic AcidProlineLong COVIDl-ornithine and l-aspartateME/CFSmetabolic dysfunctionmetabolic modelingmuscle

Identifiers

PMID40649860
PMCPMC12250530

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.