Susceptibility to SARS-CoV-2 infection in a T2-biased experimental asthma model

<bold>Background:</bold> Susceptibility of people with asthma to SARS-CoV-2 infection is controversially discussed. <bold>Aims and objectives:</bold> We aimed at investigating the role of T2 immune bias in a model of allergen-induced experimental asthma. <bold>Methods:</bold> Balb/c mice underwent an ovalbumin-induced experimental asthma protocol with or without (OVA), an adenoviral transfection with hACE2 receptor and subsequent infection with SARS-CoV-2. Control (PBS) and mice only infected with SARS-CoV-2 (SARS) were also tested. Inflammation was assessed through lung histology, BAL cytology and cytokine determination, FACS-based analysis of lung immune cells, and transcriptomics. Viral infection was evaluated by SARS-CoV-2 RT-qPCR and in situ hybridization of lung tissue. <bold>Results:</bold> Mucus-producing PAS+ goblet cells were significantly more in OVA as compared to control mice but we did not identify any differences versus OVA/SARS animals. Inflammatory immune cells of the OVA mice accumulated in the peribronchial area, while in the OVA/SARS mice they showed a wide infiltration across the entire lung. Eosinophils in the lung cell homogenate of OVA mice were significantly more compared to PBS mice, while OVA/SARS mice did not differ from PBS animals. Tbet+CD8+ T cells were significantly higher in OVA/SARS as compared to SARS mice. Additionally, OVA/SARS mice exhibited elevated levels of T2 cytokines such as IL-5 and IL-13 as compared to PBS mice. Assessment of virus load via RT-qPCR did not reveal differences between SARS and OVA/SARS mice. <bold>Conclusion:</bold> In our asthma model, we observed a heightened T2 cytokine expression upon SARS-CoV-2 infection, albeit counter-regulatory immune pathways were activated alongside unaltered virus load.