Exploring the Trascriptomic Underpinning the Effect of Biological Therapies on Sars-Cov-2 Susceptibility in Inflammatory Bowel Disease (Ibd) Patients

ABSTRACT

Introduction: The current pandemia is due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was originally identified in China in 2019, when numerous cases of atypical pneumonia were reported. Elderly and pre-existing disorders including hypertension, heart problems, diabetes, cancer, autoimmune diseases and IBD are found associated with an increased risk of COVID-19. A few clinical studies suggested that IBD and immunomodulation may reduce the susceptibility to COVID-19;however, the molecular mechanisms are not fully revealed. Aims & Methods: In this study, we attempted to identify a transcriptomic signature as candidate of the effects of IBD and different therapies on the risk of SARS-CoV-2 infection and COVID-19 severity through colonic tissue gene expression. In 2020-2022, 192 IBD patients, 115 Crohn disease (CD), 77 Ulcerative colitis (UC) and 36 Healthy Controls (HC) of the North Italy area were enrolled. Colon biopsies from inflamed and non-inflamed mucosa were collected from IBD patients and healthy mucosa samples were collected from HC. To evaluate the exposure to SARS-CoV-2, clinical data were collected and seroprevalence of anti-SARS-CoV-2 Ab were analyzed by means of multiplex technology with BioPlex 2200 Sars-Cov-2 IgG Panel (biorad, Italy). Gene expression analysis of ACE2, TMPRSS2, TMPRSS4, ADAM17 were performed by qPCR in biopsies of the three experimental groups. Result(s) In IBD patients cohort the seroprevalence of anti-SARS-CoV-2 antibodies indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy, and also a lower incidence in IBD patients in biological therapies vs. conventional ones. Gene expression analysis of the proteins involved in SARS-CoV-2 entry indicated that IBD patients treated with anti-TNF (N=72) had a lower mucosal level of SARS-CoV-2 receptor ACE2 and its sheddase ADAM17 than non-IBD subjects along with higher expression of the proteases TMPRSS2 and TMPRSS4. Moreover, vedolizumab-treated patients (N=40) showed a significant lower expression of ACE2, TMPRSS2 and TMPRSS4 than controls, whereas ADAM17 levels were similar. Conclusion(s) Data presented in our study suggest that the biologic-treated IBD population has an overall lower risk of contracting SARS-CoV-2 infection. Colonic expression of proteins involved in SARS-CoV-2 virus entry suggested an additional protective mechanism. Understanding the association of this protection profile with COVID-19 severity and the mechanisms of virus entry into the colon could reveal resistance pathways in higher-risk patient subgroups.