Gastro-intestinal manifestations of SARS-CoV-2, importance for viral replication, spread and pathogenesis.(GI-SARS-2)
- Funded by Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF)
- Total publications:0 publications
Grant number: 01KI20198A 01KI20198B
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Key facts
Disease
COVID-19Start & end year
20202021Known Financial Commitments (USD)
$280,237.45Funder
Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF)Principal Investigator
Drs. Steeve Boulant, Theodore AlexandrovResearch Location
GermanyLead Research Institution
Department für Infektiologie, Virologie Universitätsklinikum Heidelberg EMBL, The European Molecular Biology LaboratoryResearch Priority Alignment
N/A
Research Category
Pathogen: natural history, transmission and diagnostics
Research Subcategory
Pathogen morphology, shedding & natural history
Special Interest Tags
N/A
Study Type
Clinical
Clinical Trial Details
Not applicable
Broad Policy Alignment
Pending
Age Group
Unspecified
Vulnerable Population
Unspecified
Occupations of Interest
Unspecified
Abstract
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.