Altered Plasma Levels of the SARS-CoV-2-related Proteins ACE2 and TMPRSS2 in Patients with Crohn's Disease

The SARS-CoV-2 coronavirus infects cells through the cellular receptor angiotensin-converting enzyme 2 (ACE2), and the protease TMPRSS2 for the priming of viral spike protein. Thus, changes in these key proteins due to chronic conditions can increase risk for SARS-CoV2 infection; but significance of changes may differ is these changes correspond to full-length species or proteolytic fragments. Here, we determined that full-length ACE2 decreased in the plasma of uninfected Crohn's disease (CD) patients before treatment onset compared to controls. TMPRSS2 is mostly presented in plasma as full-length species and as an active peptidase fragment, but also as a prodomain fragment, which is the unique species remarkably decreased in plasma from CD patients. Patients treated with the anti-TNFα adalimumab showed recovery in ACE2 levels, while those treated with infliximab, or with the anti-IL-12/23 ustekinumab, still displayed a decrease in full-length species, as well as in cleaved fragments. Patients treated with azathioprine displayed similar ACE2 levels to that of controls, except a decrease in one of the ACE2 fragments. Uniquely, patients treated with azathioprine or with ustekinumab showed partial recovery in the reduction of the TMPRSS2-prodomain fragment characterized in treatment-naïve patients. Our data suggest that CD and common therapies are not related to increased susceptibility for SARS-CoV-2.