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

Mayte Suárez-Fariñas, Minami Tokuyama, Gabrielle Wei, Ruiqi Huang, Alexandra Livanos, Divya Jha, Anais Levescot, Haritz Irizar, Roman Kosoy, Sascha Cording, Wenhui Wang, Bojan Losic, Ryan C. Ungaro, Antonio Di'Narzo, Gustavo Martinez-Delgado, Maria Suprun, Michael J. Corley, Aleksandar Stojmirovic, Sander M. Houten, Lauren PetersMark Curran, Carrie Brodmerkel, Jacqueline Perrigoue, Joshua R. Friedman, Ke Hao, Eric E. Schadt, Jun Zhu, Huaibin M. Ko, Judy Cho, Marla C. Dubinsky, Bruce E. Sands, Lishomwa Ndhlovu, Nadine Cerf-Bensusan, Andrew Kasarskis, Jean Frederic Colombel, Noam Harpaz, Carmen Argmann, Saurabh Mehandru

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)287-301.e20
JournalGastroenterology
Volume160
Issue number1
DOIs
StatePublished - Jan 2021
Externally publishedYes

Keywords

  • COVID-19
  • GI Tract
  • IBD Medications
  • Network Analyses

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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