Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI.
Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Eaton-Fitch, Natalie et al. · The American journal of medicine · 2025 · DOI
Quick Summary
Researchers used advanced brain imaging to measure chemical imbalances in ME/CFS and long COVID patients compared to healthy people. They found that two important brain chemicals—glutamate and N-acetyl-aspartate—were significantly higher in patients with both conditions. These chemical imbalances were connected to how severe patients' symptoms were, suggesting that abnormal brain chemistry may play a role in the exhaustion and other symptoms these patients experience.
Why It Matters
This is among the first studies directly measuring brain neurochemical abnormalities in both ME/CFS and long COVID, providing objective biological evidence for the neurological basis of these conditions. Finding similar neurochemical patterns in both diseases strengthens the scientific understanding of their shared pathophysiology and may eventually guide treatment development. The correlation between brain chemistry and symptom severity validates that patient-reported symptoms have measurable biological underpinnings.
Observed Findings
Glutamate levels were significantly elevated in long COVID patients compared to healthy controls (P=.02)
Glutamate levels were significantly elevated in ME/CFS patients compared to healthy controls (P=.017)
N-acetyl-aspartate levels were significantly elevated in long COVID patients compared to healthy controls (P=.012)
No significant neurochemical differences were found between long COVID and ME/CFS patient groups
Brain neurochemical levels correlated with self-reported symptom severity measures in both patient groups
Inferred Conclusions
Imbalanced neurochemicals, particularly elevated glutamate, contribute to symptoms in both long COVID and ME/CFS
Long COVID and ME/CFS likely share overlapping underlying pathological mechanisms based on similar neurochemical abnormalities
Brain neurochemistry may serve as an objective biological marker for disease severity in these conditions
Neurochemical imbalances represent a potential therapeutic target for treatment development
Remaining Questions
Do these neurochemical abnormalities exist in other brain regions, and what is their broader spatial distribution across the brain?
What This Study Does Not Prove
This study does not prove that glutamate imbalance causes ME/CFS or long COVID symptoms—only that an association exists. It measures neurochemistry in only one brain region (posterior cingulate cortex), so abnormalities may exist elsewhere in the brain. The small sample size means findings need replication in larger populations before drawing definitive conclusions about disease mechanisms.
Are the elevated glutamate levels a cause or consequence of the disease process, and do they change over time or in response to treatment?
Can neurochemical measurements be used to distinguish ME/CFS/long COVID from other conditions with similar symptoms, and do they predict treatment response?
What specific mechanisms drive the glutamate elevation—mitochondrial dysfunction, immune activation, or other factors—and can this knowledge lead to targeted therapies?