TY - JOUR
T1 - Intestinal Inflammation Modulates the Expression of ACE2 and TMPRSS2 and Potentially Overlaps With the Pathogenesis of SARS-CoV-2–related Disease
AU - Suárez-Fariñas, Mayte
AU - Tokuyama, Minami
AU - Wei, Gabrielle
AU - Huang, Ruiqi
AU - Livanos, Alexandra
AU - Jha, Divya
AU - Levescot, Anais
AU - Irizar, Haritz
AU - Kosoy, Roman
AU - Cording, Sascha
AU - Wang, Wenhui
AU - Losic, Bojan
AU - Ungaro, Ryan C.
AU - Di'Narzo, Antonio
AU - Martinez-Delgado, Gustavo
AU - Suprun, Maria
AU - Corley, Michael J.
AU - Stojmirovic, Aleksandar
AU - Houten, Sander M.
AU - Peters, Lauren
AU - Curran, Mark
AU - Brodmerkel, Carrie
AU - Perrigoue, Jacqueline
AU - Friedman, Joshua R.
AU - Hao, Ke
AU - Schadt, Eric E.
AU - Zhu, Jun
AU - Ko, Huaibin M.
AU - Cho, Judy
AU - Dubinsky, Marla C.
AU - Sands, Bruce E.
AU - Ndhlovu, Lishomwa
AU - Cerf-Bensusan, Nadine
AU - Kasarskis, Andrew
AU - Colombel, Jean Frederic
AU - Harpaz, Noam
AU - Argmann, Carmen
AU - Mehandru, Saurabh
N1 - Publisher Copyright:
© 2021 AGA Institute
PY - 2021/1
Y1 - 2021/1
N2 - 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
AB - 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
KW - COVID-19
KW - GI Tract
KW - IBD Medications
KW - Network Analyses
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U2 - 10.1053/j.gastro.2020.09.029
DO - 10.1053/j.gastro.2020.09.029
M3 - Article
C2 - 32980345
AN - SCOPUS:85097683796
SN - 0016-5085
VL - 160
SP - 287-301.e20
JO - Gastroenterology
JF - Gastroenterology
IS - 1
ER -