SARS-CoV-2 variants mediated tissue-specific metabolic reprogramming determines the disease pathophysiology in hamster model

Seeking a nuanced understanding of host tissue-specific responses and their implications for immunopathogenicity against the SARS-CoV-2 infection was convoluted and not evaluated earlier. We delved into the intricacies of using to understand the complex relationship among acute multi-tissue injury, dysbiosis of the gut microbiota, and the resulting implications for SARS-CoV-2 variant-specific immunopathogenesis in the Golden Syrian hamster (GSH) model. Our investigation revealed increased viremia in diverse tissues of delta-infected GSH compared to the Omicron variant. Multi-omics analyses uncovered distinctive metabolic responses between the delta and omicron variants, with the former demonstrating dysregulation in synaptic transmission proteins associated with neurological disorders. Additionally, delta-infected GSH exhibited an altered fecal microbiota composition, marked by increased inflammatory-associated taxa and reduced commensal bacteria compared to the omicron variant. These findings underscore the SARS-CoV-2-mediated tissue insult, characterized by modified host metabolites, neurological protein dysregulation, and acute gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute infection.