Low, Russell N, Low, Ryan J, Akrami, Athena · Frontiers in medicine · 2023 · DOI
This review examines how Long COVID may develop through a chain reaction of immune system problems. When the virus infects the body, it can trigger ongoing inflammation that affects both the immune system and the brain, potentially causing blood clots in small vessels. This combination may explain symptoms like fatigue, brain fog, and pain that Long COVID and ME/CFS patients experience.
This study is significant because it provides a unifying biological framework connecting Long COVID and ME/CFS, two conditions with substantial symptom overlap but historically separate research bases. Understanding shared inflammatory and microglial mechanisms could accelerate development of targeted treatments and improve patient care for both conditions. The emphasis on cytokine dysregulation offers testable hypotheses for future mechanistic studies.
This review does not establish causality or validate the proposed pathways through original experimental or clinical data—it synthesizes existing literature into a theoretical model. The study does not prove that cytokine dysregulation is the primary driver of Long COVID symptoms, nor does it demonstrate that all Long COVID patients follow this particular pathophysiological trajectory. The connection between Long COVID and ME/CFS progression remains speculative and requires prospective clinical investigation.
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
Low, Russell N, Low, Ryan J, & Akrami, Athena (2023). A review of cytokine-based pathophysiology of Long COVID symptoms.. Frontiers in medicine. https://doi.org/10.3389/fmed.2023.1011936
BibTeX
@article{mecfsatlas-low-2023-review-cytokine,
author = {Low, Russell N and Low, Ryan J and Akrami, Athena},
title = {A review of cytokine-based pathophysiology of Long COVID symptoms.},
journal = {Frontiers in medicine},
year = {2023},
doi = {10.3389/fmed.2023.1011936},
note = {PubMed: 37064029},
url = {https://www.mecfsatlas.com/evidence/low-2023-review-cytokine},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/low-2023-review-cytokine
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