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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2023

Open Access 01-12-2023 | SARS-CoV-2 | Research

Differential effects of SARS-CoV-2 variants on central nervous system cells and blood–brain barrier functions

Authors: Alizé Proust, Christophe J. Queval, Ruth Harvey, Lorin Adams, Michael Bennett, Robert J. Wilkinson

Published in: Journal of Neuroinflammation | Issue 1/2023

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Abstract

Background

Although mainly causing a respiratory syndrome, numerous neurological symptoms have been identified following of SARS-CoV-2 infection. However, how the virus affects the brain and how the mutations carried by the different variants modulate those neurological symptoms remain unclear.

Methods

We used primary human pericytes, foetal astrocytes, endothelial cells and a microglial cell line to investigate the effect of several SARS-CoV-2 variants of concern or interest on their functional activities. Cells and a 3D blood–brain barrier model were infected with the wild-type form of SARS-CoV-2, Alpha, Beta, Delta, Eta, or Omicron (BA.1) variants at various MOI. Cells and supernatant were used to evaluate cell susceptibility to the virus using a microscopic assay as well as effects of infection on (i) cell metabolic activity using a colorimetric MTS assay; (ii) viral cytopathogenicity using the xCELLigence system; (iii) extracellular glutamate concentration by fluorometric assay; and (iv) modulation of blood–brain barrier permeability.

Results

We demonstrate that productive infection of brain cells is SARS-CoV-2 variant dependent and that all the variants induce stress to CNS cells. The wild-type virus was cytopathic to all cell types except astrocytes, whilst Alpha and Beta variants were only cytopathic for pericytes, and the Omicron variant cytopathic for endothelial cells and pericytes. Lastly wild-type virus increases blood–brain barrier permeability and all variants, except Beta, modulate extracellular glutamate concentration, which can lead to excitotoxicity or altered neurotransmission.

Conclusions

These results suggest that SARS-CoV-2 is neurotropic, with deleterious consequences for the blood–brain barrier integrity and central nervous system cells, which could underlie neurological disorders following SARS-CoV-2 infection.
Appendix
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Metadata
Title
Differential effects of SARS-CoV-2 variants on central nervous system cells and blood–brain barrier functions
Authors
Alizé Proust
Christophe J. Queval
Ruth Harvey
Lorin Adams
Michael Bennett
Robert J. Wilkinson
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
SARS-CoV-2
Published in
Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-023-02861-3

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