Reduced SARS-CoV-2 infection levels and pathotype specific altered antiviral transcriptional response in IBD intestinal organoids

Background IBD is characterized by altered immune reactions and infections are thought to trigger chronic inflammation in IBD. The gut represents a productive reservoir for SARS-CoV-2 and the aforementioned factors together with immunosuppression used to treat IBD are likely influencing the outcomes of IBD patients with COVID-19. Methods We used large and small intestinal organoids from ulcerative colitis and Crohn's disease patients and controls to comparatively assess infection levels and transcriptional response of the gut epithelium during SARS-CoV-2 infection. Results Our analysis showed that IBD epithelia exhibit reduced viral loads compared to controls associated with a reduced expression of SARS-CoV-2 entry factors including the host receptor ACE2. Moreover, several genes implicated in the epithelial response to viral infection are intrinsically altered in IBD potentially counteracting viral propagation. Notably, differences between IBD phenotypes exist wherein ulcerative colitis represents with induced cell death pathways and increased IL1B expression despite lower viral loads suggestive of increased epithelial stress. Conclusions Altogether our analysis shows that the IBD epithelium is not more prone to SARS-CoV-2 infection and that several antiviral response genes are intrinsically activated in IBD. Moreover, ulcerative colitis and Crohn's disease exhibit specific transcriptional differences which might explain the differing COVID-19 outcomes between IBD phenotypes.