Association between post-COVID-19 neuropsychiatric symptoms and persistent glial activation in the limbic system: a TSPO PET study, 2026, Tuomaala+

[forestglip]

Association between post-COVID-19 neuropsychiatric symptoms and persistent glial activation in the limbic system: a TSPO PET study

Spoiler: Authors

Joel Tuomaala, Maija Saraste, Emma Smith, Matilda Kuusi, Elisabet Westerberg, Eveliina Honkonen, Rahim Kargar, Sini Laaksonen, Jussi Lehto, Amelie Luoma, Markus Matilainen, Olavi Misin, Janne Atosuo, Mari Kanerva, Helena Liira, Sini Laakso, Tatiana Posharina, Virva Saunavaara, Saara Wahlroos, Johan Rajander, Laura Airas

Background
A subset of individuals experience prolonged neurological and psychiatric symptoms following SARS-CoV-2 infection, a condition referred to as long COVID (LC).

Limited evidence implicates ongoing neuroinflammatory processes as a driver of LC. This study investigates neuroinflammation in LC using translocator protein positron emission tomography (TSPO PET).

Methods
14 LC, 11 healthy control (HC) and 13 multiple sclerosis (MS) participants were included in the study. They underwent [11C]PK11195 TSPO PET and 3T magnetic resonance imaging (MRI) to evaluate glial activation, white matter (WM) pathology and brain volumetrics.

Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were measured as markers of neuronal and glial damage. LC participants completed neurological examinations and mental health assessments.

Results
TSPO availability, measured as distribution volume ratio (DVR), was not elevated in LC compared to HCs but was significantly lower in LC compared to MS (WM DVR 1.03 vs. 1.06; p = 0.007).

Individuals imaged within 16 months of SARS-CoV-2 infection showed higher WM DVR compared to those with a longer disease duration (1.05 vs. 1.02; p = 0.04).

Moreover, lower quality of life was associated with higher DVRs in the hippocampus, amygdala and thalamus (ρ = − 0.83- − 0.70), and depression and anxiety correlated positively with DVRs in the hippocampus and amygdala (ρ = 0.75–0.97).

Conclusions
LC TSPO availability did not differ from HCs in any studied brain area. However, lower WM TSPO availability in individuals with longer LC duration suggests COVID-19-associated neuroinflammation may subside with time, while the association between limbic TSPO availability and LC severity may imply a role for limbic activity in LC symptomology.

Web | DOI | PDF | Journal of Neurology | Open Access

 

[Dolphin]

Brain inflammation is unlikely to explain persistent long COVID symptoms

A new brain imaging study has found no evidence of widespread brain inflammation in patients suffering from prolonged symptoms after COVID-19 infection. Instead, the most severe long COVID symptoms were associated with increased brain activity in regions involved in mood and emotion.

www.eurekalert.org

News Release 22-May-2026

Brain inflammation is unlikely to explain persistent long COVID symptoms​

Peer-Reviewed Publication
University of Turku


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image:

The TSPO-PET image of the brain on the right shows increased glial activation in the thalamus, amygdala, and hippocampus in a long COVID patient with persistent and severe symptoms of fatigue, anxiety, and depression following SARS-CoV-2 infection. The image on the left shows a corresponding scan from an individual with milder symptoms.

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Credit: Joel Tuomaala

A new brain imaging study has found no evidence of widespread brain inflammation in patients suffering from prolonged symptoms after COVID-19 infection. Instead, the most severe long COVID symptoms were associated with increased brain activity in regions involved in mood and emotion.

Long COVID has been suspected to involve persistent brain inflammation following SARS-CoV-2 infection, potentially explaining symptoms such as fatigue, cognitive impairment, anxiety, and depression. While previous studies have suggested this possibility, direct evidence has been limited.

Researchers at the University of Turku, Finland, used advanced brain imaging techniques to investigate whether long COVID patients with persistent symptoms show signs of brain inflammation.

“We did not observe evidence of widespread brain inflammation in patients with long COVID when compared to healthy controls,” says Professor of Neuroimmunology and InFLAMES Research Flagship group leader Laura Airas, who led the study.

The study included 14 individuals with long COVID, 11 healthy controls, and 13 patients with multiple sclerosis (MS), a neurological disease known to involve brain inflammation.

All participants underwent PET imaging sensitive to neuroinflammation, along with magnetic resonance imaging (MRI) to assess brain structure and white matter changes. Blood samples were analysed for biomarkers reflecting neuronal and glial damage.

Compared to MS patients, individuals with long COVID showed significantly lower inflammatory activity in the brain’s white matter. No differences in markers of brain inflammation or neurodegeneration were observed between long COVID patients and healthy controls.

Brain inflammation may be present early after infection​

Clear signs of brain inflammation have previously been observed in neuropathological studies of severe acute COVID-19. In the current study, individuals scanned within 16 months of infection showed higher white matter inflammatory activity compared to those with longer disease duration.

According to Airas, this suggests that inflammation may be more prominent during the early phase of the disease and decrease over time.

An important finding of the study was that higher levels of depression and anxiety, as well as lower quality of life, were associated with increased cellular activity in the hippocampus and amygdala. They are brain regions involved in memory, emotional regulation, and stress responses.

These findings suggest that altered cellular activation in emotion-regulating brain regions may be linked to symptom severity in some patients with long COVID.

Toward a clearer understanding of long COVID and targeted treatments​

The researchers note that the findings refine our understanding of long COVID and challenge the idea that persistent brain inflammation is the primary driver of prolonged symptoms in all patients. Instead, the results point to a more complex disease profile, where inflammatory changes may be strongest right after infection and diminish over time.

Long COVID is a recognised condition affecting millions of people worldwide, with symptoms that can persist for months or even years after the initial infection.

The researchers suggest that patients with prolonged symptoms may benefit more from treatments targeting stress 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,” notes Airas.

The study by Airas and colleagues has been published in the Journal of Neurology.

InFLAMES Flagship is a joint initiative of the University of Turku and Åbo Akademi University, Finland. The goal of the Flagship is to integrate the immunological and immunology-related research activities to develop and exploit new diagnostic and therapeutic tools for personalised medicine. InFLAMES is part of the Research Council of Finland´s Flagship Programme.

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Journal​

Journal of Neurology

DOI​

10.1007/s00415-026-13842-w

Article Title​

Association between post-COVID-19 neuropsychiatric symptoms and persistent glial activation in the limbic system: a TSPO PET study.

Article Publication Date​

30-Apr-2026

 

[V.R.T.]

Does this study contradict or line up with what we know about the James TSPO PET study?

I remember there was low signal in the brain in that one?