Abstract
Immune dysregulation and cytokine release syndrome have emerged as pathological hallmarks of severe Coronavirus Disease 2019 (COVID-19), leading to the evaluation of cytokine antagonists as therapeutic agents. A number of immune-directed therapies being considered for COVID-19 patients are already in clinical use in chronic inflammatory conditions like inflammatory bowel disease (IBD). These considerations led us to systematically examine the intersections between COVID-19 and the GI tract during health and intestinal inflammation. We have observed that IBD medications, both biologic and non-biologic, do not significantly impact ACE2 and TMPRSS2 expression in the uninflamed intestines. Additionally, by comparing SARS CoV2-induced epithelial gene signatures with IBD-associated genes, we have identified a shared molecular subnetwork 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.
Footnotes
Competing interests: 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.
