Oxidative stress is a shared characteristic of ME/CFS and Long COVID. Article Swipe
Vishnu Shankar
,
Julie Wilhelmy
,
Ellis J. Curtis
,
Basil Michael
,
Layla Cervantes
,
Vamsee Mallajosyula
,
Ronald W. Davis
,
M Snyder
,
Shady Younis
,
William H. Robinson
,
Sadasivan Shankar
,
Paul S. Mischel
,
Hector Bonilla
,
Mark M. Davis
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2426564122
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2426564122
Over 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition marked by fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). With no clinically approved treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in 25 healthy controls, 27 ME/CFS, and 20 LC donors, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, especially in the memory subset. Using a combination of flow cytometry, RNA-seq, mass spectrometry, and systems chemistry analysis, we observed aberrations in reactive oxygen species (ROS) clearance pathways including elevated glutathione levels, decreases in mitochondrial superoxide dismutase protein levels, and glutathione peroxidase 4-mediated lipid oxidative damage. Strikingly, these redox pathways changes show sex-specific trends. While ME/CFS females exhibit higher total ROS and mitochondrial calcium levels, males have normal ROS levels, with pronounced mitochondrial lipid oxidative damage. In females, these higher ROS levels correlate with T cell hyperproliferation, consistent with the known role of elevated ROS in initiating proliferation. This hyperproliferation can be attenuated by metformin, suggesting this Food and Drug Administration (FDA)-approved drug as a possible treatment, as also suggested by a recent clinical study of LC patients. Moreover, these results suggest a shared mechanistic basis for the systemic phenotypes of ME/CFS and LC, which can be detected by quantitative blood cell measurements, and that effective, patient-tailored drugs might be discovered using standard lymphocyte stimulation assays.
Related Topics
Concepts
Coronavirus disease 2019 (COVID-19)
Oxidative stress
Stress (linguistics)
2019-20 coronavirus outbreak
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Virology
Medicine
Internal medicine
Philosophy
Linguistics
Outbreak
Disease
Infectious disease (medical specialty)
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://pubmed.ncbi.nlm.nih.gov/40627396
- OA Status
- green
- Cited By
- 8
- References
- 1
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412110744
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412110744Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1073/pnas.2426564122Digital Object Identifier
- Title
-
Oxidative stress is a shared characteristic of ME/CFS and Long COVID.Work title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-07-15Full publication date if available
- Authors
-
Vishnu Shankar, Julie Wilhelmy, Ellis J. Curtis, Basil Michael, Layla Cervantes, Vamsee Mallajosyula, Ronald W. Davis, M Snyder, Shady Younis, William H. Robinson, Sadasivan Shankar, Paul S. Mischel, Hector Bonilla, Mark M. DavisList of authors in order
- Landing page
-
https://pubmed.ncbi.nlm.nih.gov/40627396Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/12280928Direct OA link when available
- Concepts
-
Coronavirus disease 2019 (COVID-19), Oxidative stress, Stress (linguistics), 2019-20 coronavirus outbreak, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Virology, Medicine, Internal medicine, Philosophy, Linguistics, Outbreak, Disease, Infectious disease (medical specialty)Top concepts (fields/topics) attached by OpenAlex
- Cited by
-
8Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 8Per-year citation counts (last 5 years)
- References (count)
-
1Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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