Glial Activation Among Individuals with Neurological Post-acute Sequelae of Coronavirus Disease 2019: A Positron Emission Tomography Study of Brain Fog Using [F]-FEPPA

Overview

Journal Brain Behav Immun Health

Date 2025 Feb 3

PMID 39897172

Authors

Sean A P Clouston

Paul Vaska

Tesleem Babalola

John Gardus 3rd

Chuan Huang

Nicola Soriolo

Ashley Fontana

Christine DeLorenzo

Ramin Parsey

Benjamin J Luft

Affiliations

Soon will be listed here.

Abstract

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 [F]-FEPPA as an intravenous bolus and positron-emission tomography over 2 h. To measure distribution volume (V) 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 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 was higher (V = 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/cm in V (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 [F]-FEPPA could be used to support N-PASC diagnosis.

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