Gupta, Gautam, Buonsenso, Danilo, Wood, John et al. · Comprehensive Physiology · 2025 · DOI
This review examines how Long Covid causes persistent symptoms affecting multiple body systems. The research suggests that SARS-CoV-2 virus may hide in body tissues, trigger ongoing immune problems, and damage how cells produce energy, which could explain fatigue and post-exertion crashes. These mechanisms appear similar to ME/CFS, suggesting the two conditions may share common biological pathways.
This study is important because it directly compares Long Covid and ME/CFS mechanisms, suggesting findings from one condition may inform understanding of the other. Identifying shared pathways—particularly mitochondrial dysfunction and post-exertion malaise—could accelerate development of treatments applicable to both patient populations. Understanding these mechanisms may also validate ME/CFS patients' experiences by grounding symptoms in identifiable biological processes.
This review does not prove that viral persistence or specific immune markers definitively cause Long Covid symptoms—it synthesizes existing evidence of associations and proposed mechanisms. It does not establish causation from correlation, nor does it validate which proposed mechanisms are primary drivers versus secondary consequences. The strength of evidence varies across mechanisms discussed, and some proposed pathways remain speculative pending further validation.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Gupta, Gautam, Buonsenso, Danilo, Wood, John, Mohandas, Sindhu, & Warburton, David (2025). Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.. Comprehensive Physiology. https://doi.org/10.1002/cph4.70019
BibTeX
@article{mecfsatlas-gupta-2025-mechanistic-insights,
author = {Gupta, Gautam and Buonsenso, Danilo and Wood, John and Mohandas, Sindhu and Warburton, David},
title = {Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.},
journal = {Comprehensive Physiology},
year = {2025},
doi = {10.1002/cph4.70019},
note = {PubMed: 40474772},
url = {https://www.mecfsatlas.com/evidence/gupta-2025-mechanistic-insights},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/gupta-2025-mechanistic-insights
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