Estimates suggest that approximately five to ten percent of individuals develop Post-COVID syndrome following infection with SARS-CoV-2. In addition to fatigue and sleep disturbances, many affected individuals report persistent cognitive complaints that can substantially impair daily functioning and occupational performance. The underlying causes are not yet sufficiently understood. A central scientific hypothesis posits that impaired energy supply may contribute to these symptoms.
Investigation of Cellular Metabolism in the Brain
To address this question, the study team employed a specialized variant of magnetic resonance imaging (MRI) in the NEULOCO study: phosphorus magnetic resonance spectroscopy (31P-MRS). This method enables the measurement of high-energy phosphates in the brain that are essential for cellular metabolism. The focus was on adenosine triphosphate (ATP) as the primary energy carrier and phosphocreatine (PCr) as a short-term energy reservoir capable of rapidly regenerating ATP. “Using 31P-MRS, alterations in energy supply can be visualized in the living brain,” explains Prof. Dr. Gabriele Ende, Head of the Core Facility ZIPP at the Central Institute of Mental Health.
For the analysis, 27 patients with Post-COVID and 23 control participants who had fully recovered following SARS-CoV-2 infection were examined. In addition to imaging procedures, all participants completed cognitive assessments, the results of which were compared with metabolic measurements.
Evidence of Impaired Energy Supply
The findings indicate that, in individuals with Post-COVID, ATP levels are reduced relative to PCr. This suggests that the provision of energy for cerebral cellular metabolism may be compromised. These alterations were observed in the region of the cingulate cortex, a brain area involved, among other functions, in the regulation and organization of cognitive processes. “We observe an association between energy markers in the anterior cingulate cortex and cognitive performance. This suggests that impaired energy provision in this brain region may contribute to the thinking and concentration difficulties observed in Post-COVID,” states Dr. Claudia Schilling, Head of the Sleep Laboratory at the Central Institute of Mental Health.
Subgroup with Additional ME/CFS Shows Similar Patterns
Approximately half of the Post-COVID group additionally met the diagnostic criteria for ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome). In a subgroup analysis, these participants exhibited metabolic alterations similar to those observed in Post-COVID individuals without ME/CFS. This may indicate that certain biological mechanisms play a role in both patient groups.
Potential Causes Under Discussion
The researchers emphasize that the study design does not permit causal conclusions. Possible mechanisms discussed by the team include altered mitochondrial function (“the powerhouses of the cell”), inflammation-related metabolic changes, or perfusion-related influences on energy metabolism.
“Such biological findings may contribute to a better understanding of Post-COVID and support the development of more targeted therapeutic approaches in the future,” says Dr. Claudia Schilling.
Source: Press release of the Central Institute of Mental Health
