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Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures

View ORCID ProfileMichael B. VanElzakker, Hannah F. Bues, View ORCID ProfileLudovica Brusaferri, View ORCID ProfileMinhae Kim, Deena Saadi, View ORCID ProfileEva-Maria Ratai, View ORCID ProfileDarin D. Dougherty, View ORCID ProfileMarco L. Loggia
doi: https://doi.org/10.1101/2023.10.19.563117
Michael B. VanElzakker
1Division of Neurotherapeutics, Department of Psychiatry, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
5PolyBio Research Foundation, Medford, MA, USA
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  • For correspondence: mvanelzakker@mgh.harvard.edu
Hannah F. Bues
1Division of Neurotherapeutics, Department of Psychiatry, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Ludovica Brusaferri
2Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
3Department of Computer Science And Informatics, School of Engineering, London South Bank University, London, UK
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Minhae Kim
2Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Deena Saadi
1Division of Neurotherapeutics, Department of Psychiatry, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Eva-Maria Ratai
2Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Darin D. Dougherty
1Division of Neurotherapeutics, Department of Psychiatry, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Marco L. Loggia
2Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
4Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 has triggered a consequential public health crisis of post-acute sequelae of COVID-19 (PASC), sometimes referred to as long COVID. The mechanisms of the heterogeneous persistent symptoms and signs that comprise PASC are under investigation, and several studies have pointed to the central nervous and vascular systems as being potential sites of dysfunction. In the current study, we recruited individuals with PASC with diverse symptoms, and examined the relationship between neuroinflammation and circulating markers of vascular dysfunction. We used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 PASC individuals versus 43 normative healthy controls. We found significantly increased neuroinflammation in PASC versus controls across a wide swath of brain regions including midcingulate and anterior cingulate cortex, corpus callosum, thalamus, basal ganglia, and at the boundaries of ventricles. We also collected and analyzed peripheral blood plasma from the PASC individuals and found significant positive correlations between neuroinflammation and several circulating analytes related to vascular dysfunction. These results suggest that an interaction between neuroinflammation and vascular health may contribute to common symptoms of PASC.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 20, 2023.
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Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures
Michael B. VanElzakker, Hannah F. Bues, Ludovica Brusaferri, Minhae Kim, Deena Saadi, Eva-Maria Ratai, Darin D. Dougherty, Marco L. Loggia
bioRxiv 2023.10.19.563117; doi: https://doi.org/10.1101/2023.10.19.563117
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Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures
Michael B. VanElzakker, Hannah F. Bues, Ludovica Brusaferri, Minhae Kim, Deena Saadi, Eva-Maria Ratai, Darin D. Dougherty, Marco L. Loggia
bioRxiv 2023.10.19.563117; doi: https://doi.org/10.1101/2023.10.19.563117

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