Differential effects of SARS-CoV-2 variants on central nervous system cells and blood–brain barrier functions, 2023, Proust et al

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


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.




https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-023-02861-3

 

This is seriously wild. Despite having completely botched the pandemic, medicine will progress massively from it. It could have regardless, but this really all confirms to me the general pattern that learning, even scientific learning, only happens by accident, by exploring all the spaces. It's a brute force thing where individual skill is almost meaningless, it mostly needs scale and resources to look everywhere, probably multiple times. And time. And I guess literally making all the mistakes. Again and again. Intelligence truly is a social emergent phenomenon.

 

(cf FND / "functional seizures")