Sars-Cov-2 variants mediated tissue-specific metabolomic reprogramming determines the disease pathophysiology in a hamster model

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 organs an...

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Bibliographic Details
Published inBrain, behavior, and immunity
Main Authors Kaur Sardarni, Urvinder, Ambikan, Anoop T, Acharya, Arpan, Johnson, Samuel D, Avedissian, Sean N, Végvári, Ákos, Neogi, Ujjwal, Byrareddy, Siddappa N
Format Journal Article
LanguageEnglish
Published Netherlands 29.10.2024
Subjects
Gut-lung-brain axis
SARS-CoV-2
acute COVID-19
PASC
Tissue-response
Delta
Omics
Omicron
Hamster model
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Summary: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 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 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.
ISSN:1090-2139