Fig. 2.

The intestinal tract offers SARS-CoV-2 multiple entry points and routes. Various types of epithelial cells are found in the intestinal epithelial lining. Enterocytes are by far the most abundant, and they express higher amounts of ACE2 than the pulmonary alveolar cells (Xu et al., 2020b) and also express higher amounts of TMPRSS4, whereas secretory cells like the goblet cells express more TMPRSS2, its isoform (Zang et al., 2020). These two proteases also enhance membrane fusion, facilitating virion entry into the cells by endocytosis (arrow on apical enterocyte plasmalemma) through a yet uncharacterized mechanism. SARS-CoV-2 replicates most efficaciously in the enterocyte, and exocytic shedding can occur from the apical and/or the basal membrane (red arrow). Fluorescent-labelled SARS-CoV-2 particles are mostly found in mature villous absorptive enterocytes and to a lesser extent in undifferentiated stems cells (Zang et al., 2020). Enteroendocrine cells (shown in purple) exhibit lower expression levels of ACE2 and TMPRSS2/4. Once in the submucosa SARS-CoV-2 virions can find their way to the capillaries, also rich in ACE2 in their endothelial cells and pericytes (depicted in green in the lower-right corner), to reach the general circulation. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)