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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.

Authors :
Suárez-Fariñas M
Tokuyama M
Wei G
Huang R
Livanos A
Jha D
Levescot A
Irizar H
Kosoy R
Cording S
Wang W
Losic B
Ungaro RC
Di'Narzo A
Martinez-Delgado G
Suprun M
Corley MJ
Stojmirovic A
Houten SM
Peters L
Curran M
Brodmerkel C
Perrigoue J
Friedman JR
Hao K
Schadt EE
Zhu J
Ko HM
Cho J
Dubinsky MC
Sands BE
Ndhlovu L
Cerf-Bensusan N
Kasarskis A
Colombel JF
Harpaz N
Argmann C
Mehandru S
Source :
Gastroenterology [Gastroenterology] 2021 Jan; Vol. 160 (1), pp. 287-301.e20. Date of Electronic Publication: 2020 Sep 25.
Publication Year :
2021

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.)

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