key: cord-0691276-d9i0sg1s
authors: Hanrahan, Timothy P.; Lubel, John S.; Garg, Mayur
title: Letter to the Editor: Lessons from COVID-19, ACE2 and intestinal inflammation – could a virus trigger chronic intestinal inflammation?
date: 2020-07-23
journal: Clin Gastroenterol Hepatol
DOI: 10.1016/j.cgh.2020.07.036
sha: 320ecbd5d0daf8c2cfb1ff31cf1f471aa8067baf
doc_id: 691276
cord_uid: d9i0sg1s

nan

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. 2 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 (Ang II, the effector peptide of the classical RAS pathway), increased tumour necrosis factor α (TNFα), and tryptophan deficiency. 3 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. 4 Interestingly, ACE2 activity is lower in inflamed colonic biopsies of patients with inflammatory bowel disease (IBD) compared to those with normal bowel mucosa. 5 Given SARS-CoV-2 results in ACE2 alteration in mucosal membranes, it is feasible that these two pathologies may ultimately share a pro-inflammatory pathway. 5 IBD is considered a consequence of a dysregulated and inappropriate immune interaction to intestinal microorganisms, with most literature to date focussed 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. 6 When considering multi-system 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. 7 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 towards understanding any postulated role that enteric viruses may play in the pathogenesis of IBD. This warrants careful consideration.

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