Reduced ATP-to-phosphocreatine ratios in neuropsychiatric post-COVID condition: Evidence from 31P magnetic resonance spectroscopy
Plain-Language Summary
Post-COVID condition (often called Long COVID) affects a substantial number of people after SARS-CoV-2 infection, with cognitive symptoms such as brain fog and slowed thinking being especially common. One leading hypothesis is that these symptoms may be linked to problems with how cells produce and use energy, particularly within mitochondria, the structures responsible for energy generation. Until now, direct evidence of altered brain energy metabolism in Long COVID patients has been limited.
In this study, researchers used a specialized brain imaging technique to measure high-energy phosphate metabolism across the brain in people with post-COVID condition and in fully recovered controls. They found reduced markers of energy availability in a specific brain region involved in cognition and attention, the cingulate cortex. Importantly, these energy changes were associated with worse performance on cognitive tests, suggesting a biological link between altered brain metabolism and cognitive symptoms in Long COVID.
Key Findings
- Patients with post-COVID condition showed reduced ATP/PCr ratios, a marker of cellular energy balance, centered in the cingulate cortex.
- Energy metabolism was consistently reduced across anterior, mid, and posterior subdivisions of the cingulate cortex.
- Lower ATP/PCr ratios in the anterior cingulate cortex were correlated with poorer cognitive performance on standardized tests.
- Exploratory analyses suggested altered intracellular pH regulation linked to energy metabolism in patients but not in controls.
- Similar brain metabolic changes were observed in post-COVID patients who also met criteria for ME/CFS.
Study Type
Observational case–control study using advanced brain imaging and neuropsychological testing.
What This Means (and Doesn’t Mean)
These findings suggest that cognitive symptoms in post-COVID condition may be associated with impaired brain energy metabolism, particularly in regions involved in attention, cognitive control, and mental effort. The results support the idea that mitochondrial dysfunction and disrupted cellular energy regulation could play a role in Long COVID and related conditions such as ME/CFS.
However, this study does not prove that impaired energy metabolism directly causes cognitive symptoms, nor does it establish whether these changes are reversible or responsive to treatment. The sample size was relatively small, and the findings need to be confirmed in larger and more diverse populations. Further research is required to determine how these metabolic changes develop and whether they can be targeted therapeutically.
Source
Disclaimer
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