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Review of "Intestinal organoids expose heterogeneity in SARS-CoV-2 susceptibility"

Reviewers: Leandra Santos Baptista & Fabiana Avila Carneiro (Federal University of Rio de Janeiro) | 📗📗📗📗◻️

Published onMar 24, 2022
Review of "Intestinal organoids expose heterogeneity in SARS-CoV-2 susceptibility"
key-enterThis Pub is a Review of
Variable susceptibility of intestinal organoid-derived monolayers to SARS-CoV-2 infection
Description

ABSTRACTGastrointestinal effects associated with COVID-19 are highly variable for reasons that are not understood. In this study, we used intestinal organoid-derived cultures differentiated from primary human specimens as a model to examine inter-individual variability. Infection of intestinal organoids derived from different donors with SARS-CoV-2 resulted in orders of magnitude differences in virus replication in small intestinal and colonic organoid-derived monolayers. Susceptibility to infection correlated with ACE2 expression level and was independent of donor demographic or clinical features. ACE2 transcript levels in cell culture matched the amount of ACE2 in primary tissue indicating this feature of the intestinal epithelium is retained in the organoids. Longitudinal transcriptomics of organoid-derived monolayers identified a delayed yet robust interferon signature, the magnitude of which corresponded to the degree of SARS-CoV-2 infection. Interestingly, virus with the Omicron variant spike protein infected the organoids with the highest infectivity, suggesting increased tropism of the virus for intestinal tissue. These results suggest that heterogeneity in SARS-CoV-2 replication in intestinal tissues results from differences in ACE2 levels, which may underlie variable patient outcomes.

To read the original manuscript, click the link above.

Reviewer 1 (Leandra Santos Baptista & Fabiana Avila Carneiro) | 📗📗📗📗◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

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