Updated project metadata. We provide the first comprehensive analysis of nasal cell responses to SARS-COV-2 using single cell transcriptomics and proteomics. The immune response to SARS-CoV-2 is dominated by a delayed type I and III IFN response, which is too slow to contain viral replication. Cells transitioning from secretory to ciliated states are highly permissive to SARS-CoV-2, whereas goblet cells are relatively resistant. Cell-type differences in the production and response to IFN-I/III correlate with permissiveness. Pre-treatment with recombinant IFNs potently restricts SARS-CoV-2. Nasal delivery of recombinant IFNs is a promising prophylactic strategy for SARS-CoV-2