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; 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

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. 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. 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 non-biologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines. Additionally, 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. 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.