Reduced expression of COVID-19 host receptor,ACE2is associated with small bowel inflammation, more severe disease, and response to anti-TNF therapy in Crohn’s disease

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 increasedACE2mRNA in ileum with demographic features that have been associated with poor outcomes in COVID-19 including age and raised BMI.ACE2was downregulated in CD compared to controls in independent cohorts. Within CD,ACE2expression 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 bowelACE2expression was restored by anti-TNF therapy particularly in anti-TNF responders. Collectively our data suggest thatACE2downregulation is associated with inflammation and worse outcomes in CD.