Damage or changes to myelin can slow thinking, movement, and other brain functions.

“This is one of the first studies to report different myelin signal and brain neurochemical changes between long COVID, COVID-recovered-healthy controls, and healthy controls without SARS-CoV-2 infection,” the researchers wrote in their Brain, Behavior, & Immunity – Health paper.

Who Was Studied and What Researchers Found

Long COVID patients met the World Health Organization’s definition: symptoms starting within three months of infection and lasting at least two months. Most were women (14 out of 19), and they’d been sick for about nine months on average. All of them reported fatigue, with most also experiencing unrefreshing sleep (84%), concentration problems (72%), headaches (69%), and muscle aches (63%). They scored significantly worse on pain, cognitive function, and physical ability tests compared to both other groups.

The recovered group had been infected but no longer experienced long COVID symptoms. The never-infected group had no history of COVID.

When researchers compared long COVID patients to never-infected people, they found higher myelin-related signals in brain regions controlling motor function and memory. Compared to the long COVID group, recovered individuals showed even higher signals in several regions, including parts of the brainstem (like the pons and midbrain), major white matter pathways, and cerebellar areas.

Recovered individuals also showed higher myelin signals than never-infected people in areas controlling movement and attention, despite feeling fine. Earlier research found that people who recovered from COVID perform more slowly on cognitive tasks even without obvious symptoms, which these brain changes might help explain.

Other Tissue Changes After COVID Infection Detected

Brain scans also revealed differences in how water moves through tissue, another way to assess brain structure. Long COVID patients showed restricted water movement in certain regions, potentially indicating ongoing repair processes.

Recovered individuals showed different tissue patterns in areas involved in motor control and learning compared to never-infected people, even though they reported no symptoms.

Brain Chemistry After COVID

Chemical analysis revealed distinct patterns between groups. Long COVID patients had higher levels of a compound called NAA (often considered a marker of brain metabolism) but lower glutamine compared to recovered patients. During acute COVID infection, glutamine levels typically drop as the body uses it for energy and immune function. Lower glutamine in long COVID suggests ongoing depletion, while recovered patients showed higher glutamine than the long COVID group.

This chemical difference provides one of the clearest biological distinctions between still feeling sick and feeling recovered.

Activity Levels Matter

Long COVID patients with worse physical function showed lower myelin-related signals in memory-processing regions. This tracks with other research. Studies in animals and healthy humans show that physical exercise promotes myelin health, while inactivity leads to deterioration. One possibility is a feedback loop: if symptoms reduce activity, that might make it harder for the brain to bounce back. But this study can’t prove that—it only shows correlations.

Similarly, patients with worse “brain fog” showed lower myelin-related signals in areas that enable rapid thinking. Reduced myelin could directly contribute to the slower processing speed, difficulty concentrating, and mental fatigue many people describe.

Are Brain Changes From COVID Infection Permanent?

The findings show brain differences associated with COVID-19 infection in people with ongoing symptoms and those who feel recovered. Since this study looked at people only once, it can’t say whether these changes get worse, stay the same, or eventually disappear. That will require following the same people over months or years.

The brain changes offer a biological explanation for symptoms like cognitive difficulties, crushing fatigue, and physical limitations that many long COVID patients report. For recovered individuals, the findings raise questions about what recovery really means when brain scans show changes even after symptoms resolve.

Whether these alterations matter for long-term health remains unknown, but they suggest COVID’s effects on the brain extend beyond the acute illness phase — even when people feel fine.

Paper Notes

Limitations

This study examined 47 participants at a single point in time, so it can’t determine whether brain changes progress, stabilize, or improve over time. Some results are tentative and need confirmation in larger follow-up studies. The researchers note this is exploratory work meant to generate hypotheses for future research. Studies tracking the same individuals over time are needed to understand what happens to these brain changes.

Funding and Disclosures

ME Research UK (SCIO Charity Number SC036942) funded this research with financial support from The Fred and Joan Davies Bequest and The Stafford Fox Medical Research Foundation. The authors declare that funders had no role in study design, data collection, analysis, decision to publish, or manuscript preparation. The authors declare no competing interests.

Publication Details

Kiran Thapaliya, Sonya Marshall-Gradisnik, Maira Inderyas, Leighton Barnden. “Altered brain tissue microstructure and neurochemical profiles in long COVID and recovered COVID-19 individuals: A multimodal MRI study.” Brain, Behavior, & Immunity – Health 50 (2025): 101142. DOI:10.1016/j.bbih.2025.101142. National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, Queensland, Australia. Received July 7, 2025; accepted November 21, 2025; published online November 25, 2025.

Disclaimer: This article is for informational purposes only and is not intended as medical advice. The research discussed represents preliminary findings that require further study and validation. If you are experiencing persistent symptoms after COVID-19 infection, please consult with a qualified healthcare provider for proper evaluation and treatment. Do not use this information to diagnose or treat any health condition.

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