Ikeda, Gentaro, Koike-Ieki, Mariko, Inoue, Hiroyuki et al. · Open forum infectious diseases · 2026 · DOI
Researchers analyzed tiny cell particles called extracellular vesicles in blood samples from people with Long COVID, ME/CFS, and healthy controls. They observed that both Long COVID and ME/CFS groups had elevated levels of certain immune cell-derived particles and alterations in mitochondrial (energy-producing) markers within B cells and other immune cells, though the findings were not identical between groups. These preliminary results suggest there may be shared immune and metabolic changes in these conditions, but the meaning of these changes for patient health remains unclear and needs further study.
This study provides one of the first direct comparisons of immune cell-derived extracellular vesicles in both Long COVID and ME/CFS, identifying potential shared plasma biomarker signatures (elevated EV concentrations, altered leukocyte populations) and divergent mitochondrial markers. For ME/CFS patients, the observation of B cell-associated mitochondrial alterations may eventually contribute to objective diagnostic or mechanistic understanding, though such biomarkers are not yet clinically validated. The partial overlap between Long COVID and ME/CFS phenotypes supports the hypothesis that these conditions may share some pathophysiological features, though relevance to the broader ME/CFS population remains to be established.
This cross-sectional design does not establish causation; it cannot show whether EV alterations drive symptom progression or simply reflect concurrent immune activation. The study does not validate extracellular vesicle profiling as a diagnostic test or prognostic tool—it reports associations in selected cohorts, not clinical utility. Results from Long COVID and ME/CFS overlap groups may not generalise to ME/CFS patients without post-infectious onset, and case definition quality and peer review status are unreported, limiting confidence in cohort characterisation.
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 →
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Primary citation
Ikeda, Gentaro, Koike-Ieki, Mariko, Inoue, Hiroyuki, Dadhania, Arya V, El Kamari, Vanessa, Jagannathan, Prasanna, et al. (2026). Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.. Open forum infectious diseases. https://doi.org/10.1093/ofid/ofag209
BibTeX
@article{mecfsatlas-ikeda-2026-plasma-extracellular,
author = {Ikeda, Gentaro and Koike-Ieki, Mariko and Inoue, Hiroyuki and Dadhania, Arya V and El Kamari, Vanessa and Jagannathan, Prasanna and Geng, Linda N and Miglis, Mitchell G and Shafer, Robert W and Yang, Phillip C and Bonilla, Hector Fabio},
title = {Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.},
journal = {Open forum infectious diseases},
year = {2026},
doi = {10.1093/ofid/ofag209},
note = {PubMed: 42131622},
url = {https://www.mecfsatlas.com/evidence/ikeda-2026-plasma-extracellular},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-25. https://www.mecfsatlas.com/evidence/ikeda-2026-plasma-extracellular
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