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bioRxiv · 10.1101/2024.02.25.581989

TISSUE-SPECIFIC METABOLOMIC REPROGRAMMING DETERMINES THE DISEASE PATHOPHYSIOLOGY OF SARS-COV-2 VARIANTS IN HAMSTER MODEL

Sardarni, U. K.·Ambikan, A.·Acharya, A.·Johnson, S. D.·Avedissian, S. N.·Vegvari, A.·Neogi, U.·Byrareddy, S.
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Abstract

Despite significant effort, a clear understanding of host tissue-specific responses and their implications for immunopathogenicity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection has remained poorly defined. To shed light on the interaction between organs and specific 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 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 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. TeaserIn hamsters at acute infection, SARS-CoV-2 variant-specific metabolic responses and gut dysbiosis dysregulate synaptic transmission proteins.

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Sardarni, U. K., Ambikan, A., Acharya, A., Johnson, S. D., Avedissian, S. N., Vegvari, A., Neogi, U., Byrareddy, S.. 2024-02-27. TISSUE-SPECIFIC METABOLOMIC REPROGRAMMING DETERMINES THE DISEASE PATHOPHYSIOLOGY OF SARS-COV-2 VARIANTS IN HAMSTER MODEL. https://doi.org/10.1101/2024.02.25.581989

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