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Intestinal Inflammation Modulates the Expression of ACE2 and TMPRSS2 and Potentially Overlaps With the Pathogenesis of SARS-CoV-2-related Disease.
- Source :
-
Gastroenterology [Gastroenterology] 2021 Jan; Vol. 160 (1), pp. 287-301.e20. Date of Electronic Publication: 2020 Sep 25. - Publication Year :
- 2021
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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.<br />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.<br />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.<br />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.<br /> (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- 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
Angiotensin-Converting Enzyme 2 metabolism
COVID-19 enzymology
Inflammatory Bowel Diseases enzymology
Intestinal Mucosa enzymology
SARS-CoV-2 pathogenicity
Serine Endopeptidases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0012
- Volume :
- 160
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 32980345
- Full Text :
- https://doi.org/10.1053/j.gastro.2020.09.029