Reduced expression of COVID-19 host receptor, ACE2 is associated with small bowel inflammation, more severe disease, and response to anti-TNF therapy in Crohn’s disease

• Type of Material: Article
• Authors: Alka A. Potdar, Cedars-Sinai Medical Center; Shishir Dube, Cedars-Sinai Medical Center; Takeo Naito, Cedars-Sinai Medical Center; Gregory Botwin, Cedars-Sinai Medical Center; Talin Haritunians, Cedars-Sinai Medical Center; Dalin Li, Cedars-Sinai Medical Center; Shaohong Yang, Cedars-Sinai Medical Center; Janine Bilsborough, Cedars-Sinai Medical Center; Lee A. Denson, University of Cincinnati; Mark Daly, Broad Institute of MIT and Harvard; Stephan R. Targan, Cedars-Sinai Medical Center; Phillip Fleshner, Cedars-Sinai Medical Center; Jonathan Braun, Cedars-Sinai Medical Center; Subramaniam Kugathasan, Emory University; Thaddeus S. Stappenbeck, Cleveland Clinic; Dermot P. B. McGovern, Cedars-Sinai Medical Center
• Language: English
• Date: 2020-04-23
• Publisher: Cold Spring Harbor Laboratory Press
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1101/2020.04.19.20070995
• Title of Journal or Parent Work: Cold Spring Harbor Laboratory. Symposia on Quantitative Biology
• Grant/Funding Information: This work was supported by internal funds from the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute.; The Cedars-Sinai MIRIAD IBD Biobank is supported by the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [NIH/NIDDK] [grants P01 DK046763 and U01 DK062413], and The Leona M and Harry B Helmsley Charitable Trust.
• Keywords: COVID-19; non-inflammatory bowel disease; transcriptomic data; host receptor; comorbidity; Angiotensin-Converting Enzyme 2; SARS-coronavirus 2; poor outcomes; Crohn’s disease
• Research Categories: Health Sciences, Pathology; Health Sciences, Rehabilitation and Therapy; Health Sciences, Public Health; Health Sciences, Immunology

Abstract

Angiotensin-Converting Enzyme 2 (ACE2) has been identified as the host receptor for SARS-coronavirus 2 (SARS-CoV-2) which has infected millions world-wide and likely caused hundreds of thousands of deaths. Utilizing transcriptomic data from four cohorts taken from Crohn’s disease (CD) and non-inflammatory bowel disease (IBD) subjects, we observed evidence of increased ACE2 mRNA in ileum with demographic features that have been associated with poor outcomes in COVID-19 including age and raised BMI. ACE2 was downregulated in CD compared to controls in independent cohorts. Within CD, ACE2 expression was reduced in inflamed ileal tissue and also remarkably, from un-involved tissue in patients with a worse prognosis in both adult and pediatric cohorts. In active CD, small bowel ACE2 expression was restored by anti-TNF therapy particularly in anti-TNF responders. Collectively our data suggest that ACE2 downregulation is associated with inflammation and worse outcomes in CD.