A new brain imaging study has found that widespread brain inflammation is unlikely to be the primary cause of persistent long COVID symptoms. Instead, researchers discovered that patients experiencing severe long COVID symptoms showed increased brain activity in regions linked to mood and emotional regulation.
Long COVID has often been associated with symptoms such as fatigue, cognitive difficulties, anxiety, and depression. Consequently, scientists have suspected that persistent inflammation in the brain following SARS-CoV-2 infection could be driving these long-term complications. However, direct scientific evidence supporting this theory has remained limited.
To investigate further, researchers at the University of Turku in Finland used advanced brain imaging techniques to study whether long COVID patients with prolonged symptoms exhibited signs of brain inflammation.
Advanced Brain Imaging Reveals Key Findings
The research team, led by Laura Airas, examined 14 individuals with long COVID, 11 healthy participants, and 13 patients with multiple sclerosis (MS), a neurological condition known to cause brain inflammation.
“We did not observe evidence of widespread brain inflammation in patients with long COVID when compared to healthy controls,” Airas said.
The researchers conducted PET scans sensitive to neuroinflammation and magnetic resonance imaging (MRI) to evaluate brain structure and white matter changes. In addition, they analysed blood samples for biomarkers associated with neuronal and glial damage.
As per the press release, the findings showed that long COVID patients had significantly lower inflammatory activity in the brain’s white matter compared to MS patients. Moreover, researchers found no major differences in markers of brain inflammation or neurodegeneration between long COVID patients and healthy individuals.
Brain Inflammation May Decline Over Time
Although the study did not find widespread inflammation in long COVID patients, researchers noted that inflammation may occur during the early stages after infection. Previous neuropathological studies had already identified clear signs of brain inflammation in severe acute COVID-19 cases.
Interestingly, participants who underwent scans within 16 months of infection displayed higher inflammatory activity in white matter than those with a longer duration of illness. According to Airas, this observation suggests that inflammation may be more prominent shortly after infection and gradually decrease over time.
Emotional Regulation Areas Show Increased Activity
The study also revealed an important connection between mental health symptoms and brain activity. Researchers found that higher levels of anxiety and depression, along with poorer quality of life, were associated with increased cellular activity in the hippocampus and amygdala — brain regions responsible for memory, emotional regulation, and stress responses.
These findings indicate that altered activity in emotion-regulating regions of the brain may contribute to symptom severity in certain long COVID patients.
Findings May Help Shape Future Treatments
The researchers believe the study improves scientific understanding of long COVID and challenges the assumption that persistent brain inflammation is the main cause of prolonged symptoms in all patients. Instead, the results suggest that long COVID involves a more complex biological process in which inflammation may peak early and reduce over time.
Long COVID continues to affect millions of people worldwide, with symptoms persisting for months or even years after the initial infection. Therefore, researchers suggest that some patients may benefit more from treatments focused on stress management and emotional regulation rather than therapies aimed solely at reducing inflammation.
“This study highlights the need to continue investigating the complex biological mechanisms underlying long COVID. Understanding these processes is essential for developing targeted treatments,” Airas noted.
The study has been published in the Journal of Neurology.
The InFLAMES Flagship, a joint initiative of the University of Turku and Åbo Akademi University, supported the research. The initiative focuses on developing advanced diagnostic and therapeutic tools for personalised medicine under Finland’s Flagship Programme.