SARS-CoV-2 variants exhibit differential gut tropism and dysbiosis in Syrian golden hamsters 2098

Description SARS-CoV-2 is a respiratory virus that uses ACE2 protein as an entry receptor. Thus, ACE2 expression levels in different tissues should dictate the viral tropism. Interestingly, human ACE2 mRNA and protein expression are most abundant in the gastrointestinal (GI) tract. We observed that the same pattern was recapitulated in the Syrian golden hamsters, prompting us to investigate the GI tropism of SARS-CoV-2 variants of concern (VOCs). We compared ancestral Wuhan-like, highly pathogenic Delta and highly transmissible but mildly pathogenic Omicron variants for their ability to infect and cause respiratory versus GI tract pathology in hamsters. Delta VOC was the most pathogenic in the respiratory and GI tracts, followed by ancestral Wuhan-like and Omicron strains. In the GI tract, viral RNA load was significant in the proximal organs such as the esophagus and stomach, highest in the small intestine, and very little to non-detectable in the colon. Additionally, all three variants showed reduced microbial diversity in fecal matter, with the Delta variant causing the most significant decrease in both observed features and phylogenetic diversity. Our findings highlight Delta’s stronger preference for infecting the GI tract, suggesting a link between high virulence and GI tropism in SARS-CoV-2 variants of concern. Funding Sources This work is supported by DBT-BIRAC (BT/CS0007/CS/02/20) and DBT-Wellcome Trust India Alliance (IA/I/18/1/503613) grant to Shashank Tripathi. Topic Categories Mucosal and Regional Immunology (MUC)