Background. Cognitive and behavioral symptoms persisting after COVID-19 infection are recognized under the clinical definition of long-COVID. Evidence suggests this condition is associated with neuroinflammation, potentially serving as a precursor to neurodegenerative disorders. Recent studies show that PET imaging with [¹¹C]Acetate is a potential tool for astrocytic reactivity assessment in vivo, as acetate is incorporated into astrocytic metabolic pathways. The purpose of this preliminary exploratory study is to investigate the associations between long-COVID cognitive-behavioral symptoms and [¹¹C]Acetate uptake in the brain.

Methods. Forty participants with 50 years old or more (20 healthy controls and 20 age- and education- matched long-COVID patients) were recruited and underwent neuropsychological assessment and a 60-min dynamic PET/MR acquisition with [¹¹C]Acetate. Regions of interest (ROIs) were segmented using FreeSurfer (v7.4) and resampled into the PET image space. [¹¹C]Acetate images (40-60 min p.i.) were corrected for partial volume effects and standard uptake value ratios (SUVR) were estimated using the cerebellar cortex as a reference tissue. Non-parametric statistics (Mann-Whitney and Spearman Correlation) were adopted.

Results. No significant differences were observed between groups regarding age (p=0.616) years of education (p=0.512) and sex (p=0.730). Compared to controls, long-COVID participants demonstrated significant impairment in Working Memory (p=0.021) and Praxis (p=0.015) (Figure 1). Although group-wise comparisons of [¹¹C]Acetate SUVR values (Figure 2) revealed no significant differences, correlation analysis showed distinct patterns between the groups. While the control group exhibited multiple significant associations (mostly positive), the long-COVID group presented just few.

Conclusions. The cognitive profile observed in long-COVID participants, particularly regarding impairments in working memory, is consistent with previous literature. Regarding the PET imaging findings, the use of [¹¹C]Acetate for astrocyte reactivity is exploratory and requires further elucidation. The association patterns between [¹¹C]Acetate uptake and cognitive tasks observed in controls were not sustained in the long-COVID group, suggesting a potential link to cognitive impairment.