SARS-CoV-2 tropism to intestine but not gastric epithelial cells is defined by limited ACE2 expression

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) infection primarily affects the lung but can also cause gastrointestinal symptoms. In vitro experiments confirmed that SARS-CoV-2 robustly infects intestinal epithelium. However, data on infection of adult gastric epithelium is sparse and a side-by-side comparison of the infection in the major segments of the gastrointestinal tract is lacking. We provide this direct comparison in organoid-derived monolayers and demonstrate that SARS-CoV-2 robustly infects intestinal epithelium, while gastric epithelium is resistant to infection. RNA sequencing and proteome analysis pointed to ACE2 as critical factor, and indeed, ectopic expression of ACE2 increased susceptibility of gastric organoid-derived monolayers to SARS-CoV-2. ACE2 expression pattern in patient gastrointestinal biopsies mirror SARS-CoV-2 infection levels in monolayers. Thus, local ACE2 expression limits SARS-CoV-2 expression in the GI tract to the intestine, suggesting that the intestine, but not the stomach is likely to be important in viral replication and possibly transmission.