Intestinal Inflammation Modulates the Expression of ACE2 and TMPRSS2 and Potentially Overlaps With the Pathogenesis of SARS-CoV-2-related Disease.
Angiotensin-Converting Enzyme 2
/ genetics
Animals
Anti-Inflammatory Agents
/ therapeutic use
Antiviral Agents
/ therapeutic use
COVID-19
/ enzymology
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
Intestinal Mucosa
/ drug effects
Longitudinal Studies
Male
Mice
SARS-CoV-2
/ drug effects
Serine Endopeptidases
/ genetics
Signal Transduction
COVID-19 Drug Treatment
COVID-19
GI Tract
IBD Medications
Network Analyses
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
07
05
2020
revised:
14
09
2020
accepted:
14
09
2020
pubmed:
28
9
2020
medline:
9
1
2021
entrez:
27
9
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32980345
pii: S0016-5085(20)35210-0
doi: 10.1053/j.gastro.2020.09.029
pmc: PMC7516468
mid: NIHMS1632886
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Antiviral Agents
0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
287-301.e20Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK123749
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK111995
Pays : United States
Informations de copyright
Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.
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