Intestinal Inflammation Modulates the Expression of ACE2 and TMPRSS2 and Potentially Overlaps With the Pathogenesis of SARS-CoV-2-related Disease

Gastroenterology. 2021 Jan;160(1):287-301.e20. doi: 10.1053/j.gastro.2020.09.029. Epub 2020 Sep 25.

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.

Keywords: COVID-19; GI Tract; IBD Medications; Network Analyses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Antiviral Agents / therapeutic use
  • COVID-19 / drug therapy
  • COVID-19 / enzymology*
  • 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 / enzymology*
  • Inflammatory Bowel Diseases / genetics
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / enzymology*
  • Intestinal Mucosa / virology
  • Longitudinal Studies
  • Male
  • Mice
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / pathogenicity*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Antiviral Agents
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human

Supplementary concepts

  • COVID-19 drug treatment