Comparison of SARS-CoV-2 variants in primary human nasal cultures indicates Delta as most cytopathic and Omicron as fastest replicating.

In a comparative analysis of infections by SARS-CoV-2 ancestral virus and variants of concern including Alpha, Beta, Delta and Omicron, we found that variants are selected for efficiency in replication. In infections of patient-derived primary nasal cultures grown at air-liquid-interface (ALI) to model upper-respiratory infection, we show that Omicron reached highest titers at early time points, a finding that is confirmed by parallel studies of patient sampling. In both primary nasal cells and lower-respiratory cell lines infections by Delta are most damaging to the cells as indicated by syncytia formation and loss of nasal ciliary function.