Relevance of enriched expression of SARS-CoV-2 binding receptor ACE2 in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients

Ashutosh Kumar; Muneeb A. Faiq; Vikas Pareek; Khursheed Raza; Ravi K. Narayan; Pranav Prasoon; Pavan Kumar; Maheswari Kulandhasamy; Chiman Kumari; Kamla Kant; Himanshu N. Singh; Rizwana Qadri; Sada N. Pandey; Santosh Kumar

The genomic and proteomic expression of ACE2 displayed high enrichment in the lower GIT (small intestine, colon, and rectum) (Fig. 1, 2e-h, Table 1 ). It was highest in the parts of small intestine followed by the colon and the rectum, and nearly absent (negligible/low mRNA expression and undetectable protein expression) in the upper GIT components: mouth cavity (including tongue, oral mucosa, and salivary glands), esophagus, and stomach ( Fig. 1, 2a-d) . GB showed high glandular expression of ACE2, while any protein expression was undetectable in appendix, liver (hepatocytes and bile duct), and pancreas (exocrine and endocrine glandular tissue) (though minimal mRNA expression was noted) (Fig. 3) . Intense ACE2 expression was noted in the glandular cells as well as in the enterocytes in the lining epithelium of the lower GIT ( Fig. 2e-h) . The cellular expression of ACE2 was visible in the enterocyte cytoplasm and in the apical brush border (Fig. 2e -h, marked with arrow heads). The digestive system specific functional enrichment map for ACE2 gene were related to digestive functions like enzyme activity, amino acids transport, and peptide metabolism at the brush border membrane of enterocytes in the intestinal epithelium (Fig. S1, Table S1 ). . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.14.040204 doi: bioRxiv preprint