IFNB1 and infection: In conclusion, in this study we have demonstrated that in addition to remarkable between subject heterogeneity in interferon responses and viral replication, SARS-CoV-2 WA-01, SARS-CoV-2 Delta variant, and SARS-CoV-2 Omicron variant all elicit a less robust type I and III interferon response in organotypic primary bronchial AEC cultures than does human rhinovirus, and that pre-infection of AECs with HRV-16, or pre-treatment with recombinant IFN-β1 or IFN-λ2, markedly reduces SARS-CoV-2 replication.