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Review of "SARS-CoV-2 Infects Neurons, Astrocytes, Choroid Plexus Epithelial Cells and Pericytes of the Human Central Nervous System"

Reviewers: Y Kamte (UCLA) | 📒📒📒 ◻️◻️

Published onJul 01, 2024
Review of "SARS-CoV-2 Infects Neurons, Astrocytes, Choroid Plexus Epithelial Cells and Pericytes of the Human Central Nervous System"
key-enterThis Pub is a Review of
SARS-CoV-2 infects neurons, astrocytes, choroid plexus epithelial cells and pericytes of the human central nervous system
SARS-CoV-2 infects neurons, astrocytes, choroid plexus epithelial cells and pericytes of the human central nervous system
Description

Abstract SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, is associated with a range of neurological manifestations including haemorrhage, thrombosis and ischaemic necrosis and encephalitits. However, the mechanism by which this occurs is unclear. Neurological disease associated with SARS-CoV-2 infection has been proposed to occur following direct infection of the central nervous system and/or indirect sequelae as a result of peripheral inflammation. We profiled ACE2 and TMPRSS2 in brain tissue from five healthy human donors, and observed expression of these proteins in astrocytes, neurons and choroid plexus epithelium within frontal cortex and medulla. Primary human astrocytes, neurons and choroid plexus epithelial cells supported productive SARS-CoV-2 infection in an ACE2- dependent manner. Infected cells supported the full viral lifecycle, releasing infectious virus particles. In contrast, primary brain microvascular endothelial cells, pericytes and microglia were refractory to SARS-CoV-2 infection. These data support a model whereby SARS-CoV-2 is neurotropic, and this may in part explain the neurological sequelae of infection.Importance A subset of patients with COVID-19 develop neurological symptoms, but the underlying cause is poorly understood. We observed that cells within normal human brain express the SARS-CoV-2 entry factors ACE-2 and TMPRRS2, with expression mainly observed within astrocytes, neurons and choroid plexus epithelium. Primary human astrocytes, neurons and choroid plexus epithelial cells cultured in vitro supported the full SARS-CoV-2 life cycle with a range of SARS-CoV-2 variants. This study demonstrates that cells of the human central nervous system express SARS-CoV-2 entry factors in vivo and support viral infection in vitro, thus supporting a model where neurological symptoms seen in some COVID-19 patients may be as a result of direct viral infection of the central nervous system. Furthermore, these data highlight the importance of investigating the ability of therapeutics to clear virus from this potential reservoir of infection.

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Summary of Reviews: The reviewer found the study potentially informative, addressing the important question of neural cell tropism for various SARS-CoV-2 strains. However, they noted that the manuscript lacks critical information and the claims are not fully supported by the presented results. Major concerns included the need for quantification data, proper statistical analysis, and more appropriate data presentation to support the authors' conclusions. The reviewer suggested that with major and minor revisions, including more detailed methods and better labeling of images, the manuscript could be improved. They emphasized the study's potential importance in understanding neurological complications post-COVID-19, but stressed that in its current form, the data do not fully support the authors' claims.

Reviewer 1 (Yashika K…) | 📒📒📒 ◻️◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

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