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 o...

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Main Authors: Sean A.P. Clouston, Paul Vaska, Tesleem Babalola, John Gardus, III, Chuan Huang, Nicola Soriolo, Ashley Fontana, Christine DeLorenzo, Ramin Parsey, Benjamin J. Luft
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Brain, Behavior, & Immunity - Health
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666354625000031
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author Sean A.P. Clouston
Paul Vaska
Tesleem Babalola
John Gardus, III
Chuan Huang
Nicola Soriolo
Ashley Fontana
Christine DeLorenzo
Ramin Parsey
Benjamin J. Luft
author_facet Sean A.P. Clouston
Paul Vaska
Tesleem Babalola
John Gardus, III
Chuan Huang
Nicola Soriolo
Ashley Fontana
Christine DeLorenzo
Ramin Parsey
Benjamin J. Luft
author_sort Sean A.P. Clouston
collection DOAJ
description 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 (VT) 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 VT 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 VT was higher (VT = 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 VT (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.
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spelling doaj-art-a2f653c9dcb64c30a99d3b23a4db25ea2025-08-20T02:47:40ZengElsevierBrain, Behavior, & Immunity - Health2666-35462025-03-014410094510.1016/j.bbih.2025.100945Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [18F]-FEPPASean A.P. Clouston0Paul Vaska1Tesleem Babalola2John Gardus, III3Chuan Huang4Nicola Soriolo5Ashley Fontana6Christine DeLorenzo7Ramin Parsey8Benjamin J. Luft9Program in Public Health, Stony Brook University, Stony Brook, NY, 11794, USA; Department of Family, Population, and Preventive Medicine, Stony Brook University, Stony Brook, NY, 11794, USA; Corresponding author. Program in Public Health, 101 Nichols Rd., Health Sciences Center, #3Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794, USA.Department of Radiology, Stony Brook University, Stony Brook, NY, 11794, USA; Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, 11794, USAProgram in Public Health, Stony Brook University, Stony Brook, NY, 11794, USADepartment of Psychiatry, Stony Brook University, Stony Brook, NY, 11794, USADepartment of Radiology and Imaging Sciences, Emory University, Atlanta, GA, 30322, USA; Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, 30322, USAProgram in Public Health, Stony Brook University, Stony Brook, NY, 11794, USADepartment of Medicine, Stony Brook University, Stony Brook, NY, 11794, USADepartment of Psychiatry, Stony Brook University, Stony Brook, NY, 11794, USADepartment of Psychiatry, Stony Brook University, Stony Brook, NY, 11794, USADepartment of Medicine, Stony Brook University, Stony Brook, NY, 11794, USABackground: 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 (VT) 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 VT 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 VT was higher (VT = 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 VT (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.http://www.sciencedirect.com/science/article/pii/S2666354625000031Post-acute sequelae of COVID-19Respiratory infectionGlial activationTranslocator proteinEssential WorkersPositron emission tomography
spellingShingle Sean A.P. Clouston
Paul Vaska
Tesleem Babalola
John Gardus, III
Chuan Huang
Nicola Soriolo
Ashley Fontana
Christine DeLorenzo
Ramin Parsey
Benjamin J. Luft
Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [18F]-FEPPA
Brain, Behavior, & Immunity - Health
Post-acute sequelae of COVID-19
Respiratory infection
Glial activation
Translocator protein
Essential Workers
Positron emission tomography
title Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [18F]-FEPPA
title_full Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [18F]-FEPPA
title_fullStr Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [18F]-FEPPA
title_full_unstemmed Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [18F]-FEPPA
title_short Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [18F]-FEPPA
title_sort glial activation among individuals with neurological post acute sequelae of coronavirus disease 2019 a positron emission tomography study of brain fog using 18f feppa
topic Post-acute sequelae of COVID-19
Respiratory infection
Glial activation
Translocator protein
Essential Workers
Positron emission tomography
url http://www.sciencedirect.com/science/article/pii/S2666354625000031
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