Age, Inflammation, and Disease Location Are Critical Determinants of Intestinal Expression of SARS-CoV-2 Receptor ACE2 and TMPRSS2 in Inflammatory Bowel Disease

Although the respiratory tract is implicated as the primary portal of entry of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), gastrointestinal involvement is well-reported, associated with nausea, vomiting, diarrhea, and highly persistent viral particle shedding in feces.(1,2) There is critical need to establish factors determining susceptibility to Coronavirus Disease 2019 (COVID-19) in patients with inflammatory bowel disease (IBD). Age, comorbidity, disease activity, and exposure to immunomodulatory and biological therapies provide the basis for new guidelines for risk stratification and shielding.(3) We hypothesize that expression levels of the SARS-CoV-2 spike protein receptor, angiotensin-converting enzyme 2 (ACE2),(4) may also determine susceptibility to SARS-CoV-2-inflicted damage. Transmembrane serine protease 2 (TMPRSS2) primes the viral spike protein,(5) allowing for the potent binding of ACE2. Both are known to be highly expressed in healthy ileal epithelium, with lower levels in epithelial cells in the colon. We report dysregulated mucosal ACE2 and TMPRSS2 expression in the colon and ileum in IBD, and identify the critical determinants of altered expression.