Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease

Author:

Suárez-Fariñas Mayte,Tokuyama MinamiORCID,Wei Gabrielle,Huang Ruiqi,Livanos Alexandra,Jha Divya,Levescot Anais,Kosoy Roman,Irizar Haritz,Cording Sascha,Wang Wenhui,Ungaro Ryan,Di’Narzo Antonio,Martinez Gustavo,Suprun Maria,Corley Michael J.,Stojmirovic Aleksandar,Houten Sander M.ORCID,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-Benssusan Nadine,Kasarskis Andrew,Colombel Jean Frederic,Harpaz Noam,Argmann Carmen,Mehandru SaurabhORCID

Abstract

AbstractImmune dysregulation and cytokine release syndrome have emerged as pathological hallmarks of severe Coronavirus Disease 2019 (COVID-19), leading to the evaluation of cytokine antagonists as therapeutic agents. A number of immune-directed therapies being considered for COVID-19 patients are already in clinical use in chronic inflammatory conditions like inflammatory bowel disease (IBD). These considerations led us to systematically examine the intersections between COVID-19 and the GI tract during health and intestinal inflammation. We have observed that IBD medications, both biologic and non-biologic, do not significantly impact ACE2 and TMPRSS2 expression in the uninflamed intestines. Additionally, by comparing SARS CoV2-induced epithelial gene signatures with IBD-associated genes, we have identified a shared molecular subnetwork 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.

Publisher

Cold Spring Harbor Laboratory

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