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Concentration problems, brain fog, slowed thinking: cognitive complaints are among the most common and debilitating symptoms of post-COVID condition. Researchers at the Central Institute of Mental Health (CIMH) have now found evidence that the energy metabolism in the brains of those affected is measurably altered. In a study using a special magnetic resonance imaging method, patients with post-COVID condition showed an altered ratio of important energy carriers in the brain, which was correlated with performance in cognitive tests.
It is estimated that around 5 to 10 percent of people develop post-COVID condition after a SARS-CoV-2 infection. In addition to exhaustion and sleep problems, many sufferers report cognitive impairments that can significantly affect their everyday lives and work. The causes of these impairments are not yet fully understood. A central scientific hypothesis is that a disruption in cellular energy supply could be involved in the symptoms.
Investigating energy-rich phosphates in the living brain
To investigate this question, the study team at the Central Institute of Mental Health (CIMH) in Mannheim used a special variant of magnetic resonance imaging (MRI) in the NEULOCO study, known as phosphorus magnetic resonance spectroscopy (31P-MRS). This procedure makes it possible to examine certain high-energy phosphates in the living brain (“in vivo”) that are crucial for cell metabolism. The researchers were interested in adenosine triphosphate (ATP) – simply put, the “fuel of the cell” – and phosphocreatine (PCr), a “short-term energy store” that can quickly replenish ATP.
The study examined 27 patients with post-COVID condition and 23 control subjects who had fully recovered from SARS-CoV-2 infection. In addition, all participants completed cognitive tests, the results of which were compared with the metabolic measurements. “With 31P-MRS, we can measure key energy sources in the brain not only indirectly, but also quite directly. This allows us to visualize changes in energy supply in the living brain,” says Prof. Dr. Gabriele Ende, head of the Core Facility ZIPP at the CIMH, explaining the choice of method.
Key finding: reduced ATP/PCr ratio
This enabled the researchers to detect a reduced ATP to PCr ratio (ATP/PCr) in people with post-COVID condition. This suggests that the supply of energy for cell metabolism in the brain may be impaired. The changes were evident in an extensive area around the cingulate cortex, a brain structure involved in, among other things, the control and organization of thought processes. “The data suggest that this is not an isolated change, but rather a larger interconnected system in the brain,” says Dr. Wolfgang Weber-Fahr, working group leader at the CIMH.
Particularly relevant: Lower ATP/PCr levels in the anterior cingulate cortex were associated with poorer performance in cognitive tests. “We see a connection between energy markers in the anterior cingulate cortex and cognitive performance. This suggests that impaired energy supply in this region of the brain could contribute to the thinking and concentration problems associated with post-COVID,” says Dr. Claudia Schilling, head of the sleep laboratory at the CIMH.
Subgroup with additional ME/CFS shows similar patterns
About half of the post-COVID group also met the criteria for ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome), a serious illness characterized by severe fatigue and a typical worsening of symptoms after physical or mental exertion. In a subgroup analysis, these participants showed similar metabolic changes to post-COVID patients without ME/CFS. This may indicate that certain biological mechanisms play a role in both patient groups.
Study shows correlations, but no cause yet
The results support the assumption that a disruption in cellular energy supply could be an important disease mechanism in post-COVID condition. Among other things, the team discusses possible causes such as altered mitochondrial function (“powerhouses of the cells”), inflammatory metabolic changes, or circulatory influences on energy metabolism.
“It is important to emphasize that our study reveals correlations. It does not yet prove which cause is ultimately the most significant. Nevertheless, such biological clues can help to better understand post-COVID condition and develop future, more targeted therapeutic approaches,” says Dr. Claudia Schilling.
Further study: SLEEP-NEURO-PATH
In order to further elucidate the mechanisms of the disease, another study called “SLEEP-NEURO-PATH” is being conducted to investigate these brain mechanisms, but focusing exclusively on ME/CFS. Healthy participants are still being sought for this study. Contact: sleepneuropath@zi-mannheim.de
Further information: https://www.zi-mannheim.de/forschung/probanden-gesucht/gehirnstoffwechsel-und-sc...
The study is funded by the Federal Ministry of Research, Technology, and Space.
Weber-Fahr W, Dommke S, Sack M, Alzein N, Becker R, Demirakca T, Ende G, Schilling C. Reduced ATP-to-phosphocreatine ratios in neuropsychiatric post-COVID condition: Evidence from 31P magnetic resonance spectroscopy. Biol Psychiatry. 2026 Jan 10. doi:10.1016/j.biopsych.2026.01.004. Epub ahead of print.
Link: https://doi.org/10.1016/j.biopsych.2026.01.004
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