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Gastroenterology ; 160(1): 287-301.e20, 2021 01.
Article in English | MEDLINE | ID: covidwho-796100

ABSTRACT

BACKGROUND AND AIMS: The presence of gastrointestinal symptoms and high levels of viral RNA in the stool suggest active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication within enterocytes. METHODS: Here, in multiple, large cohorts of patients with inflammatory bowel disease (IBD), we have studied the intersections between Coronavirus Disease 2019 (COVID-19), intestinal inflammation, and IBD treatment. RESULTS: A striking expression of ACE2 on the small bowel enterocyte brush border supports intestinal infectivity by SARS-CoV-2. Commonly used IBD medications, both biologic and nonbiologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines. In addition, we have defined molecular responses to COVID-19 infection that are also enriched in IBD, pointing to shared molecular networks between COVID-19 and IBD. CONCLUSIONS: These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19. Preprint doi: https://doi.org/10.1101/2020.05.21.109124.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/enzymology , Inflammatory Bowel Diseases/enzymology , Intestinal Mucosa/enzymology , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/genetics , COVID-19/virology , Case-Control Studies , Clinical Trials as Topic , Cross-Sectional Studies , Disease Models, Animal , Female , Gene Regulatory Networks , Host-Pathogen Interactions , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/genetics , Intestinal Mucosa/drug effects , Intestinal Mucosa/virology , Longitudinal Studies , Male , Mice , SARS-CoV-2/drug effects , Serine Endopeptidases/genetics , Signal Transduction , COVID-19 Drug Treatment
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