Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [¹⁸F]-FEPPA

Background: This study examined the regional distribution of glial activation in essential workers with neurological post-acute sequelae of coronavirus disease 2019 (COVID-19) infections (N-PASC). Methods: We injected ≤185 MBq of [¹⁸F]-FEPPA as an intravenous bolus and positron-emission tomography over 2 h. To measure distribution volume (V_T) we recruited 24 essential workers (14 N-PASC, 10 Never-COVID-19 Controls, of whom 22 successfully placed arterial lines). Individuals with low binding affinity were excluded from this study, and V_T was adjusted for translocator protein genotype. Analyses that passed the false discovery rate are reported. Results: Participants at midlife survived mild to moderate COVID-19 without hospitalization but reported onset of post-acute sequelae of COVID-19 (PASC) for, on average, 22 months before undergoing neuroimaging. Hippocampal V_T was higher (V_T = 1.70, 95% C.I. = [1.30–2.21], p = 0.001) in participants with persistent brain fog after COVID-19, reflecting an increase of 10.58 mL/cm³ in V_T (area under the receiver-operating curve, AUC = 0.95 [0.85–1.00]). At a cutoff of 10.6, sensitivity/specificity/accuracy were 0.88/0.93/0.91. Conclusion: The results from this study imply that neuroimmune response is a distinct and identifiable characteristic of brain fog after COVID-19. Results suggest that [¹⁸F]-FEPPA could be used to support N-PASC diagnosis.