Association between post-COVID-19 neuropsychiatric symptoms and persistent glial activation in the limbic system: a TSPO PET study.
Level 4 - case-series / case-control
Case-control observational imaging study with small cohorts
PubMed 42059960 · doi:10.1007/s00415-026-13842-w
What was done
Researchers evaluated brain glial activation and neuroinflammation using [11C]PK11195 TSPO PET and 3T MRI in 14 individuals with long COVID (LC), 11 healthy controls (HC), and 13 multiple sclerosis (MS) controls. They assessed TSPO distribution volume ratio (DVR), brain volumetrics, serum neurofilament light chain (NfL), and serum glial fibrillary acidic protein (GFAP), alongside neurological and mental health assessments in LC participants.
What was found
TSPO availability did not differ significantly between LC and HCs across any studied brain region. LC TSPO availability was lower than in MS (white matter DVR 1.03 vs. 1.06; p = 0.007). LC participants imaged within 16 months of infection had higher white matter DVR than those with longer disease duration (1.05 vs. 1.02; p = 0.04). Within the LC group, lower quality of life correlated with higher DVR in the hippocampus, amygdala, and thalamus (rho = -0.83 to -0.70), while depression and anxiety correlated positively with DVR in the hippocampus and amygdala (rho = 0.75 to 0.97). Numeric findings for serum NfL and GFAP were not reported in the abstract.
Why it matters
These findings suggest that gross persistent neuroinflammation is not elevated across the whole brain in long COVID compared to healthy controls, but localized limbic glial activity may relate to neuropsychiatric symptom severity and could attenuate over time.
Limits
The study is limited by a very small sample size (14 LC participants), cross-sectional design preventing causal inference, and risk of inflated correlation coefficients in small subgroups without reported adjustment for multiple comparisons.
Cited by
- contradicts Positive TSPO scans showing microglial activation are observed in Alzheimer's disease, Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, major depressive disorder, PTSD, and long COVID.