Uncovering strain- and age-dependent innate immune responses to SARS-CoV-2 infection in air-liquid-interface cultured nasal epithelia

Continuous assessment of the impact of SARS-CoV-2 on the host at the cell -type level is crucial for understanding key mechanisms involved in host defense responses to viral infection. We investigated host response to ancestral -strain and Alpha -variant SARS-CoV-2 infections within air -liquid -interface human nasal epithelial cells from younger adults (26-32 Y) and older children (12-14 Y) using single -cell RNAsequencing. Ciliated and secretory -ciliated cells formed the majority of highly infected cell -types, with the latter derived from ciliated lineages. Strong innate immune responses were observed across lowly infected and uninfected bystander cells and heightened in Alpha -infection. Alpha highly infected cells showed increased expression of protein -refolding genes compared with ancestral -strain -infected cells in children. Furthermore, oxidative phosphorylation-related genes were down -regulated in bystander cells versus infected and mock -control cells, underscoring the importance of these biological functions for viral replication. Overall, this study highlights the complexity of cell -type-, age- and viral strain -dependent host epithelial responses to SARS-CoV-2.