Weber-Fahr et al. (2026)
- Authors: Wolfgang Weber-Fahr, Sandra Dommke, Markus Sack, Nabil Alzein, Robert Becker, Traute Demirakca, Gabriele Ende, Claudia Schilling
- Institutes: Department Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
- Publisher: Biological Psychiatry
- Link: DOI
Summary
This study offers the first direct evidence of impaired energy metabolism in the brains of patients with Post-COVID Condition (PCCo), highlighting a biological basis for cognitive symptoms like brain fog. By demonstrating reduced energy availability in the cingulate cortex, the research reinforces the theory that mitochondrial dysfunction is a core driver of the illness. Furthermore, the findings show that metabolic abnormalities in PCCo overlap significantly with those seen in ME/CFS, suggesting shared underlying mechanisms across these post-viral syndromes.
What was researched?
The study investigated high-energy phosphate metabolism in the brains of individuals with neuropsychiatric Post-COVID Condition (PCCo) to identify potential bioenergetic abnormalities.
Why was it researched?
Researchers sought to explore the hypothesis that mitochondrial dysfunction and disturbed cell energy metabolism are responsible for the cognitive and psychiatric symptoms observed in Long COVID.
How was it researched?
The team used 31P magnetic resonance spectroscopic imaging (31P-MRSI) at 3T to compare 27 PCCo patients with 23 fully recovered controls. They measured ATP-to-phosphocreatine (ATP/PCr) ratios across the brain and correlated these metabolic markers with cognitive performance tests like the Montreal Cognitive Assessment.
What has been found?
PCCo patients displayed significantly lower ATP/PCr ratios throughout the cingulate cortex, specifically in the anterior, mid, and posterior regions. Lower energy ratios in the anterior cingulate cortex were directly linked to poorer cognitive performance. Additionally, a subgroup analysis revealed that patients meeting the diagnostic criteria for ME/CFS exhibited the same metabolic impairments.
Discussion
A key finding was a unique negative relationship between intracellular pH and energy ratios found only in the patient group, suggesting a broader disruption of cellular homeostasis. The study’s cross-sectional design and small sample size are noted limitations that prevent establishing a definite cause-and-effect relationship.
Conclusion & Future Work
The results provide in vivo evidence that brain energy metabolism is impaired in PCCo and is directly associated with cognitive deficits. These findings support the development of therapies targeting mitochondrial function to treat post-viral conditions.