Shahbaz, Shima, Bozorgmehr, Najmeh, Rahmati, Amirhossein et al. · Frontiers in immunology · 2026 · DOI
Researchers analyzed immune cells from Long COVID patients with ME/CFS symptoms one year after COVID-19 infection and compared them to people who recovered normally. They found that Long COVID patients have significant problems with multiple immune cell types: fewer protective T cells, exhausted immune cells, and excessive inflammation markers. Interestingly, Long COVID patients showed different immune changes compared to people with ME/CFS from other causes, suggesting Long COVID may damage the immune system in a distinct way.
This study provides the first detailed cellular mechanism distinguishing Long COVID-associated ME/CFS from idiopathic ME/CFS, revealing that post-COVID ME/CFS involves distinct immune dysregulation patterns. Identifying the Galectin-9-TIM-3 pathway as a potential driver of immune cell depletion offers a concrete therapeutic target that could be tested in future interventions. These findings establish measurable immune biomarkers that could improve diagnosis, patient stratification, and development of targeted treatments for Long COVID.
This study does not prove that the identified immune changes are the primary cause of ME/CFS symptoms—they may be consequences of infection rather than disease drivers. The findings are correlative and limited to one timepoint (12 months post-infection); longitudinal data would be needed to establish whether these changes precede, coincide with, or follow symptom onset. The single-cell transcriptional signatures do not directly demonstrate functional impairment of these cells, which would require additional functional assays.
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
Shahbaz, Shima, Bozorgmehr, Najmeh, Rahmati, Amirhossein, Abouda, Amal, Syed, Hussain, Osman, Mohammed, et al. (2026). Single-cell analysis reveals immune remodeling of monocytes, NK cells, T cell exhaustion, and Galectin-9-associated depletion of gamma delta and mucosal-associated invariant T cells in Long COVID with ME/CFS.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1745933
BibTeX
@article{mecfsatlas-shahbaz-2026-single-cell,
author = {Shahbaz, Shima and Bozorgmehr, Najmeh and Rahmati, Amirhossein and Abouda, Amal and Syed, Hussain and Osman, Mohammed and Elahi, Shokrollah},
title = {Single-cell analysis reveals immune remodeling of monocytes, NK cells, T cell exhaustion, and Galectin-9-associated depletion of gamma delta and mucosal-associated invariant T cells in Long COVID with ME/CFS.},
journal = {Frontiers in immunology},
year = {2026},
doi = {10.3389/fimmu.2026.1745933},
note = {PubMed: 41822518},
url = {https://www.mecfsatlas.com/evidence/shahbaz-2026-single-cell},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/shahbaz-2026-single-cell
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