Stefano, George B · Medical science monitor : international medical journal of experimental and clinical research · 2021 · DOI
This review examines how long COVID causes long-term symptoms similar to those seen after other viral infections throughout history, particularly focusing on 'brain fog' and difficulty thinking clearly. By looking at past pandemics like the 1918 flu and other viral illnesses, researchers found that many infections can cause similar cognitive problems and fatigue that persist long after the initial infection. The study suggests that viruses may damage the brain's energy-producing structures (mitochondria), leading to reduced oxygen in the brain and chronic symptoms like those seen in ME/CFS and long COVID.
This study provides historical context showing that post-viral fatigue and cognitive dysfunction are not new phenomena unique to COVID-19, validating similar experiences in ME/CFS patients. Understanding shared mechanisms across different viral infections may help identify treatment targets applicable to ME/CFS and long COVID. The proposed mitochondrial dysfunction hypothesis offers a biological explanation that could guide research into energy metabolism dysfunction seen in both conditions.
This review does not prove that SARS-CoV-2 causes ME/CFS or that they are identical conditions. It does not establish direct causation between mitochondrial dysfunction and cognitive symptoms—these remain correlational observations from historical records. The study cannot confirm specific molecular mechanisms in living patients, as it relies on historical literature review rather than original experimental data.
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
Stefano, George B (2021). Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID.. Medical science monitor : international medical journal of experimental and clinical research. https://doi.org/10.12659/MSM.931447
BibTeX
@article{mecfsatlas-stefano-2021-historical-insight,
author = {Stefano, George B},
title = {Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
year = {2021},
doi = {10.12659/MSM.931447},
note = {PubMed: 33633106},
url = {https://www.mecfsatlas.com/evidence/stefano-2021-historical-insight},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/stefano-2021-historical-insight
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