Clinical aspects and host-microbiota interactions of emerging SARS-CoV-2 variants infection in hamsters

• Grant number: 22/02058-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): June 20, 2022
• Effective date (End): June 19, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Patrícia Brito Rodrigues
• Supervisor: François Trottein
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: Institut Pasteur de Lille, France
• Associated to the scholarship: 19/14342-7 - Comparison of gamma variant tropism and pathogenicity versus original SARS CoV-2 in humanized K18-ACE2 mice: role of gut microbiota, BP.DR

Abstract

Increased severity of SARS-CoV-2 infection has been observed in obese patients. However, there is scarce information about the mechanisms involved in the association between obesity and COVID-19 pathogenesis. The gut microbiota has recently emerged as an essential component during respiratory viral infections. The purpose of this project is to investigate the impact of obesity on gut microbiota profiles and correlate changes with COVID-19-like severity. To this end, (high fat diet) obese and lean hamsters will be infected with SARS-CoV-2 and clinical parameters will be studied. Feces from non-infected and infected hamsters will be collected at different time points (early and late time points) post infection for microbiota characterization. Unbiased shotgun metagenomics and metabolomics will be performed. The viral load in the lung, colon and liver will be analyzed by quantitative RT-PCR. The gut barrier will be studied by measuring translocation of bacteria and LPS, mucus thickness and quantification of tight junction components (RT-qPCR, immunohistochemistry). Systemic inflammation (cytokines, acute phase proteins) will be measured by ELISA and proteomics. Using an in-house, R- and Python-based bioinformatics pipeline, we will correlate microbial and metabolite datasets with parameters of infection severity. To study the role of the "dysbiotic" microbiota in disease severity the gut microbiota from obese hamsters will be transfered to lean hamsters before SARS-CoV-2 infection. This study should allow us to better decipher the consequences of obesity on COVID-19 severity and decipher the potential role of the gut microbiota's functionality in disease outcomes. (AU)