Differential immunometabolic responses to Delta and Omicron SARS-CoV-2 variants in golden syrian hamsters
Rajesh Rajaiah,
Kabita Pandey,
Arpan Acharya,
Anoop Ambikan,
Narendra Kumar,
Reema Guda,
Sean N. Avedissian,
Luis J. Montaner,
Samuel M. Cohen,
Ujjwal Neogi,
Siddappa N. Byrareddy
Affiliations
Rajesh Rajaiah
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
Kabita Pandey
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
Arpan Acharya
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
Anoop Ambikan
The Systems Virology Lab, Department of Laboratory Medicine, Division of Clinical Microbiology, ANA Futura, Karolinska Institutet, 141 52 Stockholm, Sweden
Narendra Kumar
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
Reema Guda
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
Sean N. Avedissian
Antiviral Pharmacology Laboratory, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA
Luis J. Montaner
Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA
Samuel M. Cohen
Havlik Wall Professor of Oncology, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
Ujjwal Neogi
The Systems Virology Lab, Department of Laboratory Medicine, Division of Clinical Microbiology, ANA Futura, Karolinska Institutet, 141 52 Stockholm, Sweden
Siddappa N. Byrareddy
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA; Havlik Wall Professor of Oncology, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Corresponding author
Summary: Delta (B.1.617.2) and Omicron (B.1.1.529) variants of SARS-CoV-2 represents unique clinical characteristics. However, their role in altering immunometabolic regulations during acute infection remains convoluted. Here, we evaluated the differential immunopathogenesis of Delta vs. Omicron variants in Golden Syrian hamsters (GSH). The Delta variant resulted in higher virus titers in throat swabs and the lungs and exhibited higher lung damage with immune cell infiltration than the Omicron variant. The gene expression levels of immune mediators and metabolic enzymes, Arg-1 and IDO1 in the Delta-infected lungs were significantly higher compared to Omicron. Further, Delta/Omicron infection perturbed carbohydrates, amino acids, nucleotides, and TCA cycle metabolites and was differentially regulated compared to uninfected lungs. Collectively, our data provide a novel insight into immunometabolic/pathogenic outcomes for Delta vs. Omicron infection in the GSH displaying concordance with COVID-19 patients associated with inflammation and tissue injury during acute infection that offered possible new targets to develop potential therapeutics.
