Risk for COVID-19 Vulnerability in Patients with Inflammatory Bowel Disease: Assessing Alterations in ACE2 and...

Chronic inflammatory conditions often involve the dysregulation of key enzymes, including serine proteases such as transmembrane serine protease 2 (TMPRSS2) and the angiotensin converting enzyme 2 (ACE2), which are key proteins implicated in the cellular entry mechanism of SARS-CoV-2. It remains uncertain whether the gastrointestinal symptoms observed in COVID-19 patients result from direct viral infection of the gastrointestinal tract, a process that may be exacerbated by altered expression of ACE2 or TMPRSS2. In this review, we explore the interplay among ACE2 and TMPRSS2 in the context of inflammatory bowel disease (IBD), including their roles in disease pathology and response to therapy. We also examine methodological approaches for assessing whether protease alterations contribute to increased susceptibility to infection, considering that TMPRSS2 exists in inactive (zymogen) and active forms. Furthermore, while membrane-bound ACE2 facilitates viral entry, soluble ACE2 fragments may act as decoys, preventing virus-receptor interaction. Therefore, the interpretation of changes in full-length versus cleaved forms of ACE2 and related enzymes is critical for understanding vulnerability to SARS-CoV-2 infection.