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Authors: Lamers et al

Link to paper: https://www.biorxiv.org/content/10.1101/2020.04.25.060350v1

Journal/ Pre-Print: BioRxiv

Tags: Cell Biology, Gut, Inflammation, Virology

Research Highlights 

1. SARS-CoV and SARS-CoV-2 can infect small intestinal organoid cultures

2. ACE2 is highly expressed in differentiated organoid cultures compared to expanding organoids, but infectivity remains the same

3. Transcriptomic analysis of SARS-CoV-2-infected small intestinal organoid cultures results in an interferon signature 60 hours post-infection

Summary 

Subsets of COVID-19 patients have gastrointestinal manifestations, meriting further study of SARS-CoV-2 in the intestine. Intestinal enterocytes highly express ACE2, which is the receptor of the spike protein of SARS-CoV-2. Lamers et al found that SARS-CoV and SARS-CoV-2 could infect human small intestinal organoids. ACE2 expression was increased in differentiated organoids, which did not translate into increased infectivity. The authors identified that 60 hours post-infection with SARS-CoV-2, organoid cultures had an interferon signature, which was more robust than with SARS-CoV. This study identifies the gut epithelium as a site of infection, perhaps explaining the gastrointestinal symptoms of some COVID-19 patients.

Impact for SARS-CoV2/COVID19 research efforts

Understand the virology and/or cell biology of SARS-CoV2/COVID19: This study explores SARS-CoV-2 infection in small intestinal organoids.

Study Type

· In vitro study

Strengths and limitations of the paper

Novelty: This study has three main points of novelty. Firstly, the authors show that differentiated intestinal organoids upregulate ACE2 expression. Additionally, Lamers et al describe the Type I/III interferon signature elicited following SARS-CoV-2 infection, which is not observed in SARS-CoV infection. Thirdly, they interestingly investigate the interdependency between SARS-CoV-2 infection and ACE2 receptor levels.

Standing in the field: There are multiple reports indicating that certain COVID-19 patients develop gastrointestinal symptoms. There is supporting literature for SARS-CoV-2 infection in

the intestine (Lin, Gut, 2020; Xiao, Gastroenterol, 2020) as well as for high ACE2 expression in intestinal epithelial cells (Qi, BBRC, 2020). This paper provides a novel functional characterization of intestinal organoids infected with SARS-CoV-2, offering a potential explanation for the gastrointestinal symptoms in COVID-19 patients.

Appropriate statistics: Yes

Viral model used: The viral strain used was BetaCoV/Munich/BavPat1/2020 for SARS-Cov-2 and isolate HKU 39849 for SARS-CoV.

Translatability: Not particularly translatable.

Main limitations: 1. It would be interesting to include downregulated genes following SARS-CoV-2 infection.

2. The study is performed on organoids derived from intestinal tumors. It would be interesting to interrogate whether these findings directly reflect the physiological setting.

3. The authors do not explain the mechanism through which the virus itself reaches the gastrointestinal tract.

4. Quantification of dsRNA colocalization with APOA1 and Ki67 would be useful.