Abstract
There is increasing evidence of gastrointestinal (GI) infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We surveyed the co-expression of SARS-CoV-2 entry genes ACE2 and TMPRSS2 throughout the GI tract to assess potential sites of infection. Publicly available and in-house single-cell RNA-sequencing datasets from the GI tract were queried. Enterocytes from the small intestine and colonocytes showed the highest proportions of cells co-expressing ACE2 and TMPRSS2. Therefore, the lower GI tract represents the most likely site of SARS-CoV-2 entry leading to GI infection.
Highlights
COVID-19, the disease caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has rapidly spread throughout the world and was declared a pandemic by the World HealthOrganization, leading to a rapid surge in the efforts to understand the mechanisms of transmission, methods of prevention, and potential therapies
Analysis of scRNA-seq was performed separately for each gastrointestinal (GI) segment and available cell identities from the original studies were assigned to the new clusters after confirming the expression of relevant marker genes (Figure 1)
Higher proportions of esophageal columnar cells—which were mostly from Barrett’s esophagus samples—co-expressed ACE2 and TMPRSS2 compared to the native squamous epithelium (Figure 2)
Summary
COVID-19, the disease caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has rapidly spread throughout the world and was declared a pandemic by the World HealthOrganization, leading to a rapid surge in the efforts to understand the mechanisms of transmission, methods of prevention, and potential therapies. We aimed to investigate the co-expression of ACE2 (encoding angiotensin converting enzyme 2) and TMPRSS2 (encoding transmembrane serine protease 2), the products of which are required for SARS-CoV-2 entry into mammalian cells [7], from single-cell RNA sequencing (scRNA-seq) datasets of five different parts of the GI tract: esophagus, stomach, pancreas, small intestine, and colon/rectum. We found predominant co-expression of ACE2 and TMPRSS2 in the enterocytes of the lower GI tract, with progenitor and stem-like epithelial cells demonstrating highest proportions of ACE2, TMPRSS2, and TMPRSS4 co-expression, especially in the small intestine, which suggests a potential mechanism for GI manifestations of acute COVID-19 infection.
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