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Review 2: "Neuroinflammation in Post-Acute Sequelae of COVID-19 (PASC) as Assessed by [11C]PBR28 PET Correlates with Vascular Disease Measures"

The reviewers found the study to be interesting and original given it provides evidence of neuroinflammation in people with post-acute sequelae of COVID-19.

Published onJan 20, 2024
Review 2: "Neuroinflammation in Post-Acute Sequelae of COVID-19 (PASC) as Assessed by [11C]PBR28 PET Correlates with Vascular Disease Measures"
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Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures
Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures
Description

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.

RR:C19 Evidence Scale rating by reviewer:

  • Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review:

The authors of this preprint measured neuroinflammation, systemic immunity and vascular disease in a small cohort of long COVID patients using, respectively, TSPO-PET and blood/plasma/serum panels.

This is a very interesting study, and quite unique as, finally, someone is looking into central immunity in COVID. 

Methods are strong, and the group is very experienced in this type of studies. The results are convincing and well presented. The main finding is the convincing association between brain inflammation and vascular disease (less so with systemic immunity).

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