Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease
Michael J Corley,
Joshua R Friedman,
Eric E. Schadt,
Huaibin M Ko,
Marla C. Dubinsky,
Bruce E. Sands,
Lishomwa C. Ndhlovu,
Jean Frederic Colombel,
Posted 23 May 2020
bioRxiv DOI: 10.1101/2020.05.21.109124 (published DOI: 10.1053/j.gastro.2020.09.029)
Posted 23 May 2020
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 non-biologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines. Additionally, 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. ### Competing Interest Statement SM and JFC have an unrestricted, investigator-initiated grant from Takeda Pharmaceuticals to examine novel homing mechanisms to the GI tract. RCU has served as an advisory board member or consultant for Eli Lilly, Janssen, Pfizer and Takeda. Mount Sinai co-authors (from Genetics and Genomics, Icahn Institute for Data Science and Genomic Technology, Human Immune Monitoring Center, Population Health Science and Policy, Division of Gastroenterology, Pediatric GI and Hepatology, Susan and Leonard Feinstein IBD Clinical Center at Icahn School of Medicine at Mount Sinai) were partially funded as part of research alliance between Janssen Biotech and The Icahn School of Medicine at Mount Sinai. MC, AS, JP and CB are employees at Research and Development. and JRF is a former employee at Janssen Research and Development and is currently employed at Alnylam Pharmaceuticals. MD is a consultant for Janssen. BES discloses consulting fees from 4D Pharma, Abbvie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, BoehringerIngelheim, 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. MCD discloses consulting fees from Abbvie, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, BoehringerIngelheim, Celgene, Ferring, Genentech, Gilead, Hoffmann-La Roche, Janssen, Pfizer, Prometheus Biosciences, Takeda, Target PharmaSolutions and research funding from Abbvie, Janssen, Pfizer, Prometheus Biosciences Takeda. Dr. 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.
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