Research led by Kiran Thapaliya (Griffith University)

Study Shows Structural Differences In COVID Patients Months After Infection, Even Among Those Who ‘Feel Fine’

In A Nutshell

• The study can’t determine if these brain changes are permanent, progressive, or temporary since it only examined people once
• Australian researchers scanned 47 people (19 with long COVID, 12 recovered, 16 never infected) and found brain structure differences in all three groups
• People who feel fully recovered still showed brain changes compared to never-infected individuals, particularly in areas controlling movement and attention
• Long COVID patients with worse physical function and more severe “brain fog” had lower myelin-related signals in specific brain regions

Brain scans of people who had COVID-19 show differences in brain structure months after infection, according to a small study from Australia. Even people who feel fully recovered showed measurable brain changes compared to those who never caught the virus. The long COVID group also showed differences in certain brain chemicals compared with the recovered group.

Scientists at Griffith University examined brain scans from 47 people: 19 with long COVID, 12 who recovered without ongoing symptoms, and 16 who never had COVID. Using multiple imaging techniques on a powerful MRI scanner, they discovered changes in the protective coating around nerve fibers, tissue structure, and brain chemical levels.

That protective coating, called myelin, works like insulation on electrical wires. It helps signals zip through the brain quickly and efficiently. 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.