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

Kaur Sardarni U, Ambikan AT, Acharya A, Johnson SD, Avedissian SN, Végvári Á, Neogi U, Byrareddy SN

Brain Behav Immun 123 (-) 914-927 [2025-01-00; online 2024-10-29]

Despite significant effort, a clear understanding of host tissue-specific responses and their implications for immunopathogenicity against the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) variant infection has remained poorly defined. To shed light on the interaction between tissues and SARS-CoV-2 variants, we sought to characterize the complex relationship among acute multisystem manifestations, dysbiosis of the gut microbiota, and the resulting implications for SARS-CoV-2 variant-specific immunopathogenesis in the Golden Syrian Hamster (GSH) model using multi-omics approaches. Our investigation revealed the presence of increased SARS-CoV-2 genomic RNA 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 neurocognitive disorders. Additionally, delta-infected GSH exhibited an altered fecal microbiota composition, marked by increased inflammation-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 gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute infection.

PubMed 39481495

DOI 10.1016/j.bbi.2024.10.032

Crossref 10.1016/j.bbi.2024.10.032

pii: S0889-1591(24)00674-3