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 - Funding Information:
Funding This work was supported by the following grants: NIH/NIDDK R01 123749 (Saurabh Mehandru). Additional support was provided by K23KD111995 (RCU) and a Career Development Award from the Crohn's and Colitis Foundation (RCU). Carmen Argmann and Mayte Suárez-Fariñas were supported by a Litwin Pioneers award grant. Carmen Argmann, Lauren Peters, and Eric E. Schadt were supported in part by The Leona M. and Harry B. Helmsley Charitable Trust. Minami Tokuyama was supported by the Digestive Disease Research Foundation. The sampling of the Inflammatory Bowel Disease cohort (Crohn's disease and ulcerative colitis) was jointly designed as part of the research alliance between Janssen Biotech, Inc. and The Icahn School of Medicine at Mount Sinai. Beyond this exception, no other funders had a role in analyses design and interpretation. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Conflict of interest Saurabh Mehandru and Jean Frederic Colombel have an unrestricted, investigator-initiated grant from Takeda Pharmaceuticals to examine novel homing mechanisms to the GI tract. Ryan C. Ungaro has served as an advisory board member or consultant for Eli Lilly, Janssen, Pfizer and Takeda. Mayte Suárez-Fariñas, Roman Kosoy, Bojan Losic, Antonio Di'Narzo, Maria Suprun, Lauren Peters, Sander M. Houten, Ke Hao, Eric E. Schadt, Jun Zhu, Marla C. Dubinsky, Bruce E. Sands, Andrew Kasarskis, Noam Harpaz and Carmen Argmann were partially funded as part of research alliance between Janssen Biotech and The Icahn School of Medicine at Mount Sinai. Mark Curran, Aleksandar Stojmirovic, Jacqueline Perrigoue, and Carrie Brodmerkel are employees at Research and Development. Joshua R. Friedman is a former employee at Janssen Research and Development and is currently employed at Alnylam Pharmaceuticals. Marla Dubinsky is a consultant for Janssen. Bruce E. Sands discloses consulting fees from 4D Pharma, AbbVie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Boston Pharmaceuticals, Capella Biosciences, Celgene, Celltrion Healthcare, EnGene, Ferring, Genentech, Gilead, Hoffmann-La Roche, Immunic, Ironwood Pharmaceuticals, Janssen, Lilly, Lyndra, MedImmune, Morphic Therapeutic, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Palatin Technologies, Pfizer, Progenity, Prometheus Laboratories, Redhill Biopharma, Rheos Medicines, Seres Therapeutics, Shire, Synergy Pharmaceuticals, Takeda, Target PharmaSolutions, Theravance Biopharma R&D, TiGenix, Vivelix Pharmaceuticals; honoraria for speaking in CME programs from Takeda, Janssen, Lilly, Gilead, Pfizer, Genetech; research funding from Celgene, Pfizer, Takeda, Theravance Biopharma R&D, Janssen. Marla C. Dubinsky discloses consulting fees from AbbVie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Celgene, Ferring, Genentech, Gilead, Hoffmann-La Roche, Janssen, Pfizer, Prometheus Biosciences, Takeda, and Target PharmaSolutions; and research funding from AbbVie, Janssen, Pfizer, Prometheus Biosciences Takeda. Jean Frederic Colombel reports receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Allergan, Inc. Ferring Pharmaceuticals, Shire, and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Geneva, Genentech, Janssen Pharmaceuticals, Landos, Ipsen, Imedex, Medimmune, Merck, Novartis, O Mass, Otsuka, Pfizer, Shire, Takeda, Tigenix, Viela bio; and holds stock options in Intestinal Biotech Development and Genfit. The remaining authors disclose no conflicts.
Funding Information:
Funding This work was supported by the following grants: NIH / NIDDK R01 123749 (Saurabh Mehandru). Additional support was provided by K23KD111995 (RCU) and a Career Development Award from the Crohn’s and Colitis Foundation (RCU). Carmen Argmann and Mayte Suárez-Fariñas were supported by a Litwin Pioneers award grant. Carmen Argmann, Lauren Peters, and Eric E. Schadt were supported in part by The Leona M. and Harry B. Helmsley Charitable Trust . Minami Tokuyama was supported by the Digestive Disease Research Foundation. The sampling of the Inflammatory Bowel Disease cohort (Crohn’s disease and ulcerative colitis) was jointly designed as part of the research alliance between Janssen Biotech, Inc. and The Icahn School of Medicine at Mount Sinai. Beyond this exception, no other funders had a role in analyses design and interpretation. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai .
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
UR - http://www.scopus.com/inward/record.url?scp=85097683796&partnerID=8YFLogxK
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 -