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Modelling SARS-CoV-2 CNS infection

Nature Medicine https://doi.org/10.1038/s41591-021-01443-1 (2021)

Respiratory symptoms of SARS-CoV-2 infections are well studied, but the origins of associated neurological complications remain less clear. Previous reports on brain organoids concluded that most neural cells are not infected by SARS-CoV-2. However, choroid plexus epithelial cells, immune cells and neurovascular cells in the brain are vulnerable. Gleeson and colleagues now show that the vascular cells, or pericytes, perform important functions in the central nervous system (CNS), maintain the blood–brain barrier, regulate inflammatory responses and interact with neighbouring neurons and astrocytes.

Having shown that human pericyte-like cells (PLCs) could be infected with SARS-CoV-2, the authors integrated them into cortical organoids. Under homeostasis, PLCs maintained their morphology and functions as expected and promoted maturation of astrocytes. When exposed to SARS-CoV-2, only the organoids that contained PLCs were prone to infection, and normal cortical organoids did not show viral replication. The astrocyte population became vulnerable to infection by the presence of PLCs and increasingly underwent apoptosis or activated inflammatory signalling.

Together, the authors identify PLCs as an interesting target and promoter of SARS-CoV-2 invasion in the CNS, which might also enable its spread to other cell types.

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Correspondence to Christine Weber.

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Weber, C. Modelling SARS-CoV-2 CNS infection. Nat Cell Biol 23, 927 (2021). https://doi.org/10.1038/s41556-021-00756-0

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