Pathogenesis and microbiome characterization of SARS-CoV-2 variants in K18-hACE2 transgenic mice 9174

Abstract Description The COVID-19 pandemic, caused by the SARS-CoV-2, has led to the emergence of multiple variants with distinct characteristics. Understanding the differential impacts of these SARS-CoV-2 variants is essential for developing effective prevention and treatment strategies. This study investigated the differing pathologies of the original Wuhan strain and the Omicron variant of SARS-CoV-2 using a K18-hACE2 transgenic mouse model. We compared mortality rates, viral loads, and histopathological changes in lung and tracheal tissues, while also focusing on alterations in the respiratory and digestive tract microbiota based on the strains. To achieve this, we analyzed microbiome samples from the lungs and intestines. Our results demonstrated significant differences in disease severity between the Wuhan and Omicron variants. Microbiome analyses revealed distinct shifts in the lung and intestinal microbiota corresponding to each variant, suggesting that microbiome dynamics may influence disease outcomes. This comparative study highlights the critical role of the microbiome in affecting disease severity and host responses to viral infections. Distinct microbial shifts associated with infections from various SARS-CoV-2 variants were identified, indicating potential microbiome-related mechanisms that could be targeted to improve disease outcomes. Funding Sources Supported by the National Research Foundation of Korea grants (NRF-2021M3A9H3015688, NRF-2021M3A9D3026428, NRF-2023R1A2C3003825, and RS-2024-00342560) and the Korea Research Institute of Chemical Technology grant (K-GRC GO! KRICT project BSF24-113). Topic Categories Viral Immunology (VIR)