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Authors: Krüger, J,. et al  

Journal/ Pre-Print:bioRxiv preprint  

TagsImmunology/Immunity, Gut, Stem Cells, Therapeutics 

Research Highlights  

  1. Pluripotent stem cell derived-Human intestinal organoids (PSC-HIO) support productive infection with SARS-CoV2 in a cell-type specific manner 

  1. Remdesivir and EKI, but not famotidine impedes SARS-CoV2 pathogenesis in PSC-HIOs 

  1. SARS-CoV2, with the exception of goblet cells, productively infects different epithelial cell types. Enteroendocrine cells in addition to enterocytes were infected by SARS-CoV2 indicating that the virus affects hormone secretion.  

Summary 

The authors report that SARS-CoV2 in addition to infecting only the enterocytes (Lamers MM, et al. Science 2020as previously reported, also infect the other epithelial sub-types such as enteroendocrine cells and paneth cells in gastrointestinal tissue, with various intensity. Goblet cells display weak ACE2 expression and are not productively infected by SARS-CoV2. In vitro differentiated PSC-HIOs provide a better 3D model system for drug testing over the traditional stem cell derived intestinal organoids as they express multiple cell types. Additionally, the authors report that Remdesivir and EK1 block SARS-CoV2 pathogenesis in PSC-HIOs.  

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19  

Understand the virology and/or cell biology of SARS-CoV2/COVID19 

Inhibit of SARS-CoV2/COVID19 transmission 

Study Type  

In vitro study 

Strengths and limitations of the paper 

Novelty: SARS-CoV2 infects multiple cell types in the gastrointestinal tissue in addition to just the enterocytes as previously reported.  

Standing in the field:Provides additional information on different epithelial cell types of the gastrointestinal tissue infected by SARS-CoV2  

Appropriate statistics: Mostly a descriptive study stating that SARS-CoV2 productively infects multiple intestinal epithelial cell types. Since there was no mention of technical or biological replicates, difficult to assess the statistics employed.  

Viral model used:BetaCoV/Netherlands/01/NL/2020  

Translatability:Not close to translational potential yet. But the PSC-HIO model described can be a viable tool for compound testing 

Main limitations: 

1. No mention of technical/biological replicates giving rise to the question of reproducibility.  

2. More immunofluorescent pictures required to verify virus infectivity of the organoids.