Yong, Shin Jie · ACS chemical neuroscience · 2021 · DOI
This paper suggests that long-COVID symptoms may be caused by damage to the brainstem, a part of the brain that controls basic functions like breathing, heart rate, and digestion. The authors propose that the coronavirus may directly infect the brainstem or cause inflammation there, and because brain cells heal slowly, this damage could persist long after the initial infection. This theory could help explain why long-COVID patients experience lasting fatigue, breathing problems, and other widespread symptoms.
This hypothesis is important because it offers a testable mechanistic framework that could unite many seemingly disparate long-COVID symptoms under a single anatomical dysfunction. For ME/CFS researchers and patients, it provides a potential biological explanation that parallels brainstem abnormalities previously implicated in ME/CFS itself, suggesting common pathophysiological pathways across post-viral illnesses.
This paper does not prove that brainstem dysfunction causes long-COVID—it presents a hypothesis based on reviewed literature, not original experimental evidence. The presence of viral RNA in autopsy samples does not establish causation of specific symptoms, and the paper does not rule out other proposed mechanisms (viral persistence, autoimmunity, endothelial dysfunction) or demonstrate that brainstem damage is necessary or sufficient for long-COVID development.
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
Yong, Shin Jie (2021). Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis.. ACS chemical neuroscience. https://doi.org/10.1021/acschemneuro.0c00793
BibTeX
@article{mecfsatlas-yong-2021-persistent-brainstem,
author = {Yong, Shin Jie},
title = {Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis.},
journal = {ACS chemical neuroscience},
year = {2021},
doi = {10.1021/acschemneuro.0c00793},
note = {PubMed: 33538586},
url = {https://www.mecfsatlas.com/evidence/yong-2021-persistent-brainstem},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/yong-2021-persistent-brainstem
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