Abstract
Abstract The intricate interplay between neutrophils and diverse SARS-CoV-2 variants offers insights into immunopathogenesis and potential therapeutic interventions in SARS-CoV-2 infection. Utilizing our COVID-19 feline model, we hypothesize that neutrophil dysregulation and the release of neutrophil extracellular traps (NETs) are highly strain-dependent in domestic cats. Specific-pathogen-free cats (n=8) were inoculated with SARS-CoV-2 (n=3 B.1.617.2/Delta; n=3 XBB.1.5/Omicron) or vehicle (n=2). Plasma, bronchoalveolar lavage, and lung tissues were collected over 5 days. Flow cytometric analysis of neutrophil subsets in blood, BAL, and tissues revealed functional and phenotypic changes (CXCR2+CXCR4-CCR5+) in Delta vs. Omicron vs. vehicle. Detection of NETs using MPO-DNA ELISA indicates significant elevations at 4dpi and 5dpi in the plasma and BAL of Delta and Omicron cats when compared to vehicle. Multiplex immunoassay conducted on BAL revealed significant elevation of pro-inflammatory cytokines including TN