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Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease

Mayte Suárez-Fariñas, View ORCID ProfileMinami Tokuyama, Gabrielle Wei, Ruiqi Huang, Alexandra Livanos, Divya Jha, Anais Levescot, Roman Kosoy, Haritz Irizar, Sascha Cording, Wenhui Wang, Ryan Ungaro, Antonio Di’Narzo, Gustavo Martinez, Maria Suprun, Michael J. Corley, Aleksandar Stojmirovic, View ORCID ProfileSander M. Houten, Mark 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-Benssusan, Andrew Kasarskis, Jean Frederic Colombel, Noam Harpaz, Carmen Argmann, View ORCID ProfileSaurabh Mehandru
doi: https://doi.org/10.1101/2020.05.21.109124
Mayte Suárez-Fariñas
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Minami Tokuyama
3The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
4Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Gabrielle Wei
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Ruiqi Huang
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Alexandra Livanos
3The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
4Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Divya Jha
3The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
4Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Anais Levescot
5Inserm, UMR1163, Laboratory of Intestinal Immunity and Institute Imagine, Paris, France
6Université de Paris, Paris, France
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Roman Kosoy
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Haritz Irizar
7University College London, Department Mental Health Sciences Unit, London, UK
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Sascha Cording
5Inserm, UMR1163, Laboratory of Intestinal Immunity and Institute Imagine, Paris, France
6Université de Paris, Paris, France
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Wenhui Wang
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Ryan Ungaro
3The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Antonio Di’Narzo
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Gustavo Martinez
3The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
4Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Maria Suprun
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Michael J. Corley
8Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
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Aleksandar Stojmirovic
9Janssen R&D, Spring House, PA, USA
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Sander M. Houten
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Mark Curran
9Janssen R&D, Spring House, PA, USA
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Carrie Brodmerkel
9Janssen R&D, Spring House, PA, USA
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Jacqueline Perrigoue
9Janssen R&D, Spring House, PA, USA
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Joshua R. Friedman
9Janssen R&D, Spring House, PA, USA
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Ke Hao
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Eric E. Schadt
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Jun Zhu
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Huaibin M. Ko
11Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Judy Cho
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
3The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
10The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Marla C. Dubinsky
3The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Bruce E. Sands
3The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Lishomwa Ndhlovu
8Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
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Nadine Cerf-Benssusan
5Inserm, UMR1163, Laboratory of Intestinal Immunity and Institute Imagine, Paris, France
6Université de Paris, Paris, France
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Andrew Kasarskis
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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Jean Frederic Colombel
3The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
4Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Noam Harpaz
11Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Carmen Argmann
1Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
2Icahn Institute for Data Science and Genomic Technology, New York City, NY, USA
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  • For correspondence: saurabh.mehandru@mssm.edu carmen.argmann@mssm.edu
Saurabh Mehandru
3The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
4Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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  • ORCID record for Saurabh Mehandru
  • For correspondence: saurabh.mehandru@mssm.edu carmen.argmann@mssm.edu
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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.

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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, Roman Kosoy, Haritz Irizar, Sascha Cording, Wenhui Wang, Ryan Ungaro, Antonio Di’Narzo, Gustavo Martinez, Maria Suprun, Michael J. Corley, Aleksandar Stojmirovic, Sander M. Houten, Mark 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-Benssusan, Andrew Kasarskis, Jean Frederic Colombel, Noam Harpaz, Carmen Argmann, Saurabh Mehandru
bioRxiv 2020.05.21.109124; doi: https://doi.org/10.1101/2020.05.21.109124
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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, Roman Kosoy, Haritz Irizar, Sascha Cording, Wenhui Wang, Ryan Ungaro, Antonio Di’Narzo, Gustavo Martinez, Maria Suprun, Michael J. Corley, Aleksandar Stojmirovic, Sander M. Houten, Mark 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-Benssusan, Andrew Kasarskis, Jean Frederic Colombel, Noam Harpaz, Carmen Argmann, Saurabh Mehandru
bioRxiv 2020.05.21.109124; doi: https://doi.org/10.1101/2020.05.21.109124

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