Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID.
Stefano, George B · Medical science monitor : international medical journal of experimental and clinical research · 2021 · DOI
Quick Summary
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.
Why It Matters
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.
Observed Findings
Altered cognition ('brain fog') appears as a common symptom across multiple historical viral pandemics including Russian flu, Spanish flu, and encephalitis lethargica
Similarities exist between chronic fatigue syndrome symptoms and cognitive complaints reported in long COVID
Viral infections may share common neural targeting mechanisms that persist across different viruses and time periods
Cerebral hypoxia potentially resulting from mitochondrial dysfunction has been proposed as a mechanism in long COVID
Inferred Conclusions
Post-infectious neurological and psychiatric sequelae represent a recurring pattern across multiple pandemics, suggesting shared viral mechanisms rather than unique COVID phenomena
Mitochondrial dysfunction and resulting cerebral hypoxia may be a unifying mechanism explaining cognitive dysfunction across different post-viral conditions
Neural tropism appears to be an evolutionary advantage for certain viruses, potentially explaining why cognitive symptoms appear consistently in post-viral syndromes
Remaining Questions
What specific viral proteins or mechanisms trigger mitochondrial dysfunction across different viral infections?
Are the historical descriptions of post-flu cognitive symptoms directly comparable to modern long COVID brain fog using standardized cognitive assessments?
What This Study Does Not Prove
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 →