Hippocampal subfield volume alterations and associations with severity measures in long COVID and ME/CFS: A 7T MRI study.
Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Eaton-Fitch, Natalie et al. · PloS one · 2025 · DOI
Quick Summary
Researchers used advanced brain imaging to compare a part of the brain called the hippocampus in long COVID patients, ME/CFS patients, and healthy people. They found that certain areas of the hippocampus were larger in both patient groups compared to healthy controls, and these size differences were linked to how severe symptoms like fatigue, pain, and memory problems were. This suggests that changes in brain structure might explain some of the cognitive difficulties these patients experience.
Why It Matters
This study provides neurobiological evidence that brain structural changes in the hippocampus may underlie the cognitive and memory impairments reported by ME/CFS and long COVID patients. The findings suggest these two conditions share similar pathophysiological mechanisms, which could advance understanding of disease mechanisms and potentially inform treatment strategies targeting cognitive dysfunction.
Observed Findings
Left hippocampal subfield volumes (subiculum head, presubiculum head, molecular layer hippocampus head, and whole hippocampal head) were significantly larger in both long COVID and ME/CFS patients compared to healthy controls
Hippocampal subfield volumes were similar between long COVID and ME/CFS patient groups, suggesting shared neurobiological features
Significant associations were found between hippocampal subfield volumes and severity of pain, fatigue, concentration impairment, unrefreshing sleep, and reduced physical function
Illness duration correlated with hippocampal subfield volume changes in both patient groups
Inferred Conclusions
Hippocampal structural alterations may contribute to neurocognitive impairment experienced by ME/CFS and long COVID patients
Long COVID and ME/CFS share similar patterns of hippocampal changes, suggesting overlapping pathophysiological mechanisms
Hippocampal volume changes correlate with multiple symptom severity measures, supporting a link between brain structure and clinical symptoms
Remaining Questions
Are the observed hippocampal volume increases present before symptom onset, or do they develop as a consequence of chronic illness?
What cellular or molecular mechanisms underlie the hippocampal volume enlargement in these conditions?
What This Study Does Not Prove
This study does not establish causation—larger hippocampal volumes could be a consequence of illness rather than a cause of cognitive symptoms. The cross-sectional design cannot determine whether these brain changes preceded symptom onset or developed afterward. The study also cannot explain the mechanism by which volume changes produce cognitive impairment.