Fevang, Børre, Wyller, Vegard Bruun Bratholm, Mollnes, Tom Eirik et al. · Frontiers in immunology · 2021 · DOI
This study tracked 200 teenagers with mononucleosis (caused by Epstein-Barr virus) for 6 months to understand why some developed chronic fatigue. Researchers found that teenagers who developed chronic fatigue showed persistent signs of immune system activation and inflammation, particularly elevated levels of RANTES (a signaling protein) and other inflammatory markers, both at the start of illness and 6 months later.
This longitudinal study provides immunological evidence that ME/CFS developing after EBV infection involves persistent immune dysregulation, specifically T-cell activation and chronic inflammation. Identifying biomarkers like RANTES and elevated CRP in the CF+ group may help researchers develop targeted treatments and clinicians better predict which acute EBV patients will develop chronic fatigue.
This study does not prove that elevated RANTES or inflammation directly causes chronic fatigue—only that they are associated with it. It does not establish whether these immune abnormalities are the primary driver of fatigue, a consequence of reduced physical activity, or a marker of other underlying processes. The study also does not clarify whether these findings apply to adult-onset ME/CFS or non-EBV-triggered cases.
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
Fevang, Børre, Wyller, Vegard Bruun Bratholm, Mollnes, Tom Eirik, Pedersen, Maria, Asprusten, Tarjei Tørre, Michelsen, Annika, et al. (2021). Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2021.715102
BibTeX
@article{mecfsatlas-fevang-2021-lasting-immunological,
author = {Fevang, Børre and Wyller, Vegard Bruun Bratholm and Mollnes, Tom Eirik and Pedersen, Maria and Asprusten, Tarjei Tørre and Michelsen, Annika and Ueland, Thor and Otterdal, Kari},
title = {Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue.},
journal = {Frontiers in immunology},
year = {2021},
doi = {10.3389/fimmu.2021.715102},
note = {PubMed: 34987499},
url = {https://www.mecfsatlas.com/evidence/fevang-2021-lasting-immunological},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/fevang-2021-lasting-immunological
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