Ongoing brain inflammation is probably not the reason why some people continue to feel unwell long after a COVID-19 infection, according to a study published in the Journal of Neurology. Instead, researchers found that the most troubling symptoms seem to be linked to changes in brain areas that control mood and emotion.
What the Researchers Wanted to Know
After COVID-19, many patients continued to report lingering problems like exhaustion, brain fog, anxiety, and depression. Some scientists believed these symptoms might be caused by inflammation that stayed in the brain long after the virus was gone. Until now, though, there hasn’t been direct proof either way. To dig deeper, a team at the University of Turku in Finland used advanced scanning technology to look inside the brains of people living with long COVID.
How the Study Worked
The researchers worked with three groups of people, including 14 people with long COVID, 11 healthy people for comparison and 13 people with multiple sclerosis (MS), a condition known to cause brain inflammation
Each participant had two types of brain scans: a PET scan, which can pick up signs of inflammation in the brain; and an MRI, which shows the brain’s structure and any damage to its white matter. The team also took blood samples to check for chemical signs of nerve or brain cell damage.
What They Found
The results were surprising. The brains of long COVID patients didn’t show widespread inflammation when compared to healthy people. “We did not observe evidence of widespread brain inflammation in patients with long COVID when compared to healthy controls,” said Professor Laura Airas, who led the study.
Compared with MS patients, the long COVID group actually had much less inflammation in the brain’s white matter. And when measured against the healthy volunteers, there was no real difference in markers of inflammation or brain cell damage.
Inflammation May Show Up Early Then Fade
There was one interesting twist. People who were scanned within 16 months of their COVID infection showed somewhat higher inflammation in their white matter than those whose infection had been longer ago.
According to Airas, this hints that inflammation may be stronger in the early weeks and months after infection, then gradually settle down over time. That fits with earlier post-mortem studies of people who had severe COVID, which did find clear signs of brain inflammation soon after infection.
A Link to Mood and Emotion
The team uncovered another important clue. Patients with worse depression, more anxiety, and a lower quality of life had more cellular activity in two specific brain areas: the hippocampus and the amygdala. These regions help us process memories, handle emotions, and manage stress. In other words, the people who felt worst weren’t necessarily the most inflamed. They had changes in the parts of the brain that shape how we feel.
What This Means for Treatment
These findings could change how doctors think about helping long COVID patients. If inflammation isn’t the main problem for people whose symptoms last a long time, then anti-inflammatory drugs may not be the best answer. Treatments that focus on stress, mood, and emotional wellbeing might be more useful.
The researchers stress that long COVID is complicated. It affects millions of people around the world, and symptoms can drag on for months or even years. There likely isn’t one single cause, which is why more research is needed.
“This study highlights the need to continue investigating the complex biological mechanisms underlying long COVID. Understanding these processes is essential for developing targeted treatments,” noted Airas.
Tuomaala, J., Saraste, M., Smith, E. et al. Association between post-COVID-19 neuropsychiatric symptoms and persistent glial activation in the limbic system: a TSPO PET study. J Neurol 273, 298 (2026). https://doi.org/10.1007/s00415-026-13842-w