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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.
Suárez-Fariñas, Mayte; Tokuyama, Minami; Wei, Gabrielle; Huang, Ruiqi; Livanos, Alexandra; Jha, Divya; Levescot, Anais; Irizar, Haritz; Kosoy, Roman; Cording, Sascha; Wang, Wenhui; Losic, Bojan; Ungaro, Ryan C; Di'Narzo, Antonio; Martinez-Delgado, Gustavo; Suprun, Maria; Corley, Michael J; Stojmirovic, Aleksandar; Houten, Sander M; Peters, Lauren; Curran, Mark; Brodmerkel, Carrie; Perrigoue, Jacqueline; Friedman, Joshua R; Hao, Ke; Schadt, Eric E; Zhu, Jun; Ko, Huaibin M; Cho, Judy; Dubinsky, Marla C; Sands, Bruce E; Ndhlovu, Lishomwa; Cerf-Bensusan, Nadine; Kasarskis, Andrew; Colombel, Jean-Frederic; Harpaz, Noam; Argmann, Carmen; Mehandru, Saurabh.
  • Suárez-Fariñas M; Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York; Icahn Institute for Data Science and Genomic Technology, New York City, New York.
  • Tokuyama M; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Wei G; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Huang R; Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York; Icahn Institute for Data Science and Genomic Technology, New York City, New York.
  • Livanos A; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Jha D; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Levescot A; Inserm, UMR1163, Laboratory of Intestinal Immunity and Institute Imagine, Paris, France; Université de Paris, Paris, France.
  • Irizar H; University College London, Department Mental Health Sciences Unit, London, UK.
  • Kosoy R; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Cording S; Inserm, UMR1163, Laboratory of Intestinal Immunity and Institute Imagine, Paris, France; Université de Paris, Paris, France.
  • Wang W; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Losic B; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Ungaro RC; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Di'Narzo A; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Martinez-Delgado G; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Suprun M; Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Corley MJ; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York.
  • Stojmirovic A; Janssen R&D, Spring House, Pennsylvania.
  • Houten SM; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Peters L; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Curran M; Janssen R&D, Spring House, Pennsylvania.
  • Brodmerkel C; Janssen R&D, Spring House, Pennsylvania.
  • Perrigoue J; Janssen R&D, Spring House, Pennsylvania.
  • Friedman JR; Janssen R&D, Spring House, Pennsylvania.
  • Hao K; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Schadt EE; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Zhu J; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Ko HM; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Cho J; Icahn Institute for Data Science and Genomic Technology, New York City, New York; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medi
  • Dubinsky MC; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Sands BE; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Ndhlovu L; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York.
  • Cerf-Bensusan N; Université de Paris, Paris, France.
  • Kasarskis A; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Colombel JF; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Harpaz N; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Argmann C; Icahn Institute for Data Science and Genomic Technology, New York City, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: carmen.argmann@mssm.edu.
  • Mehandru S; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: saurabh.mehandru@mssm.edu.
Gastroenterology ; 160(1): 287-301.e20, 2021 01.
Article in English | MEDLINE | ID: covidwho-796100
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Inflammatory Bowel Diseases / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 / Intestinal Mucosa Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Limits: Animals / Female / Humans / Male Language: English Journal: Gastroenterology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Inflammatory Bowel Diseases / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 / Intestinal Mucosa Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Limits: Animals / Female / Humans / Male Language: English Journal: Gastroenterology Year: 2021 Document Type: Article