Intestinal Inflammation Modulates the Expression of ACE2 and TMPRSS2 and Potentially Overlaps With the Pathogenesis of SARS-CoV-2–related Disease
Por:
Suárez-Fariñas M., Tokuyama M., Wei G., Huang R., Livanos A., Jha D., Levescot A., Irizar H., Kosoy R., Cording S., Wang W., Losic B., Ungaro R.C., Di'Narzo A., Martinez-Delgado G., Suprun M., Corley M.J., Stojmirovic A., Houten S.M., Peters L., Curran M., Brodmerkel C., Perrigoue J., Friedman J.R., Hao K., Schadt E.E., Zhu J., Ko H.M., Cho J., Dubinsky M.C., Sands B.E., Ndhlovu L., Cerf-Bensusan N., Kasarskis A., Colombel J.-F., Harpaz N., Argmann C., Mehandru S.
Publicada:
1 ene 2021
Resumen:
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 © 2021 AGA Institute
Filiaciones:
Suárez-Fariñas M.:
Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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, NY, United States
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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, NY, United States
Huang R.:
Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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, NY, United States
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Jha D.:
The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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, United Kingdom
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, NY, United States
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, NY, United States
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, NY, United States
Ungaro R.C.:
The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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, NY, United States
Martinez-Delgado G.:
The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Suprun M.:
Center for Biostatistics, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Corley M.J.:
Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, United States
Stojmirovic A.:
Janssen R&D, Spring HousePA, United States
Houten S.M.:
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, NY, United States
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, NY, United States
Curran M.:
Janssen R&D, Spring HousePA, United States
Brodmerkel C.:
Janssen R&D, Spring HousePA, United States
Perrigoue J.:
Janssen R&D, Spring HousePA, United States
Friedman J.R.:
Janssen R&D, Spring HousePA, United States
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, NY, United States
Schadt E.E.:
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, NY, United States
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, NY, United States
Ko H.M.:
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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, NY, United States
The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Dubinsky M.C.:
The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Sands B.E.:
The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Ndhlovu L.:
Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, United States
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, NY, United States
Colombel J.-F.:
The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Harpaz N.:
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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, NY, United States
Mehandru S.:
The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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