GI-SARS-2 - Gastrointestinal manifestations of SARS-CoV-2, relevance to viral replication, spread and pathogenesis.

Although there are accumulating evidence that the intestinal epithelium is infected by SARS-CoV-2, the importance of this enteric phase for virus-induced pathologies, spreading and prognosis remain unknown. Here, we will engage in the comprehensive analysis of SARS-CoV-2 life-cycle in the human intestinal epithelium. (1) we will evaluate if there are infectious virus particles in stool. (2) we will develop standardized protocols to establish a robust measure for enteric virus shedding. (3) in organoids models, we will characterize how SARS-CoV-2 infects, replicates and is released from intestinal epithelial cells. This will provide the molecular basis of the enteric lifecycle and will enable us to determine the origin of the enteric phase (fecal/oral transmission vs. spreading from lung to gut). To these goals, we will exploit a pipeline combining single cell sequencing and spatial transcriptomics which we developed to study host-virus interaction. Combined with in-situ measurement of immune response in biopsies, we will define whether exacerbated gut inflammation contributes to the lung pathology observed in patients through cytokine storm-induced cytopathic effects. We anticipate that understanding the enteric phase of SARS-CoV-2 will provide us with critical pieces of evidence to outline novel perspectives to treat the disease and eradicate the virus. Most importantly, quantifying the relevance of fecal transmission and its link to SARS-CoV-2 etiology is urgently needed to implement epidemiological and societal measures aiming at monitoring and controlling the virus.