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

9 patients with diabetes mellitus. 15 [Sufficient data on glycemic control in COVID-19 patients is lacking for now, impaired glycemic control was stated as an independent risk factor predicting morbidity and mortality in SARS patients with diabetes mellitus. 35 ] ACE2 mediated downregulation of SGLT1 in intestinal epithelium prevents hyperglycemia in rat models of the diabetes mellitus. 36, 37 Though direct evidence is lacking in terms of the effect of SARS-CoV-2 binding on ACE2 on its signaling cascades, however, substantiation from SARS-CoV-1 studies (for SARS) suggests that it can downregulate ACE2 expression. 21 Such an eventuality can lead to upregulation of SGLT1 thereby precipitating hyperglycemia. 36, 37 [SGLT1 inhibitors are being used in treatment of diabetes mellitus, their use in COVID-19 patients may need a rethinking for the dose adjustments. 38 ] Our data showed undetectable expression of ACE2 protein in insulin producing Islets of Langerhans of the pancreas raising an insulin independent possibility of dysregulated intestinal SGLT1 transporters. This bolsters the rationale behind diabetes related increased morbidity/mortality in COVID-19 patients. Apart from intestine SGLT1 is known to be widely expressed in other human tissues like proximal tubule of kidney, heart, and liver (proteinatlas.org/ENSG00000100170-SLC5A1/tissue) where it regulates the glucose absorption. An ACE2-mediated dysregulation of SGLT1 in COVID-19 patients warrants further investigation.