Lessons From COVID-19, ACE2, and Intestinal Inflammation: Could a Virus Trigger Chronic Intestinal Inflammation?
Authors: Timothy P. Hanrahan, John S. Lubel, Mayur Garg
Journal: Clinical Gastroenterology and Hepatology (2020)

We read with interest the comprehensive review by D'Amico et al1D'Amico F. et al.Clin Gastroenterol Hepatol. 2020; 18: 1663-1672Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar on diarrhea during coronavirus disease-19 (COVID-19) infection, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).1D'Amico F. et al.Clin Gastroenterol Hepatol. 2020; 18: 1663-1672Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar It is now established that SARS-CoV-2 infectivity is mediated by an interaction between viral spike proteins and ACE2 expressed on target mucosal membranes, with subsequent shedding of the ACE2 ectodomain following cellular entry.2Hoffmann M. et al.Cell. 2020; 181: 271-280Abstract Full Text Full Text PDF PubMed Scopus (13557) Google Scholar Multiple downstream effects of this interaction may perpetuate inflammatory response, including reduced Ang 1-7 levels (the effector peptide of the alternative renin-angiotensin system [RAS] pathway), elevated angiotensin II (the effector peptide of the classical RAS pathway), increased tumor necrosis factor-α, and tryptophan deficiency.3Garg M. et al.Gastroenterol. 2020 Apr 27; Google Scholar Given it has previously been shown that all components of the RAS can be identified in enteric mucosa biopsies, suggesting locally active intestinal RAS, it is perhaps unsurprising that the SARS-CoV-2 enteric interaction is sufficient enough to initiate a symptomatic inflammatory response.4Garg M. et al.Gut. 2019; 69 (gutjnl-2019-318512)PubMed Google Scholar Interestingly, ACE2 activity is lower in inflamed colonic biopsies of patients with inflammatory bowel disease compared with those with normal bowel mucosa.4Garg M. et al.Gut. 2019; 69 (gutjnl-2019-318512)PubMed Google Scholar Given SARS-CoV-2 results in ACE2 alteration in mucosal membranes, it is feasible that these 2 pathologies may ultimately share a proinflammatory pathway.4Garg M. et al.Gut. 2019; 69 (gutjnl-2019-318512)PubMed Google Scholar Inflammatory bowel disease is considered a consequence of a dysregulated and inappropriate immune interaction to intestinal microorganisms, with most literature to date focused on bacterial dysbiosis. Recent recognition that both eukaryotic viruses and bacteriophages contribute significantly to the gut microbiome, and the fact that phages are closely associated with bacterial virulence, raises the possibility that alterations may perturb symbiosis and generate a dysregulated immune response.5Ungaro F. et al.United European Gastroenterol J. 2019; 7: 999-1007Crossref PubMed Scopus (36) Google Scholar When considering multisystem consequences of COVID-19, perpetuation of inflammation and fibrosis in the lungs has been described, placing affected individuals at risk of long-term respiratory morbidity.6George P.M. et al.Lancet Respir Med. 2020; 8: 457-481Google Scholar The persistence of intestinal inflammation and development of fibrosis, and implications for long-term gastrointestinal morbidity, remain to be seen. The study of this potential phenomenon may hold vital clues toward understanding any postulated role that enteric viruses may play in the pathogenesis of inflammatory bowel disease. This warrants careful consideration. Diarrhea During COVID-19 Infection: Pathogenesis, Epidemiology, Prevention, and ManagementClinical Gastroenterology and HepatologyVol. 18Issue 8PreviewThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechanism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Full-Text PDF