Klein, Jon, Wood, Jamie, Jaycox, Jillian R et al. · Nature · 2023 · DOI
Researchers studied 275 people with and without long COVID to understand what happens in the immune system. They found that people with long COVID have different patterns of immune cells and antibodies, including stronger responses to past viral infections like Epstein-Barr virus, and lower levels of the stress hormone cortisol. Using computer analysis, they identified specific immune markers that could help identify who has long COVID.
This study provides objective, measurable immune biomarkers associated with long COVID, which could accelerate diagnosis and pathophysiologic understanding relevant to post-viral syndromes broadly. For ME/CFS patients specifically, identifying immune dysfunction patterns offers potential for developing targeted treatments and distinguishing long COVID from other post-infectious fatigue syndromes.
This study does not establish whether the observed immune abnormalities cause long COVID symptoms or are merely epiphenomena; it does not prove these biomarkers will be clinically useful for diagnosis in individual patients; and the cross-sectional design cannot determine whether immune dysfunction precedes, accompanies, or follows symptom development. Additionally, findings from SARS-CoV-2 infection may not fully translate to other post-viral syndromes including ME/CFS.
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
Klein, Jon, Wood, Jamie, Jaycox, Jillian R, Dhodapkar, Rahul M, Lu, Peiwen, Gehlhausen, Jeff R, et al. (2023). Distinguishing features of long COVID identified through immune profiling.. Nature. https://doi.org/10.1038/s41586-023-06651-y
BibTeX
@article{mecfsatlas-klein-2023-distinguishing-features,
author = {Klein, Jon and Wood, Jamie and Jaycox, Jillian R and Dhodapkar, Rahul M and Lu, Peiwen and Gehlhausen, Jeff R and Tabachnikova, Alexandra and Greene, Kerrie and Tabacof, Laura and Malik, Amyn A and Silva Monteiro, Valter and Silva, Julio and Kamath, Kathy and Zhang, Minlu and Dhal, Abhilash and Ott, Isabel M and Valle, Gabrielee and Peña-Hernández, Mario and Mao, Tianyang and Bhattacharjee, Bornali and Takahashi, Takehiro and Lucas, Carolina and Song, Eric and McCarthy, Dayna and Breyman, Erica and Tosto-Mancuso, Jenna and Dai, Yile and Perotti, Emily and Akduman, Koray and Tzeng, Tiffany J and Xu, Lan and Geraghty, Anna C and Monje, Michelle and Yildirim, Inci and Shon, John and Medzhitov, Ruslan and Lutchmansingh, Denyse and Possick, Jennifer D and Kaminski, Naftali and Omer, Saad B and Krumholz, Harlan M and Guan, Leying and Dela Cruz, Charles S and van Dijk, David and Ring, Aaron M and Putrino, David and Iwasaki, Akiko},
title = {Distinguishing features of long COVID identified through immune profiling.},
journal = {Nature},
year = {2023},
doi = {10.1038/s41586-023-06651-y},
note = {PubMed: 37748514},
url = {https://www.mecfsatlas.com/evidence/klein-2023-distinguishing-features},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/klein-2023-distinguishing-features
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