Age-specific nasal epithelial responses to SARS-CoV-2 infection

Children seldom develop severe respiratory failure from SARS-CoV-2, whereas mortality remains high in people over 85. Using ex vivo cultured nasal epithelial cells (NECs) from paediatric (<12 years), adult (30–50 years) and older adult (>70 years) donors, the study identifies age-specific differences in cellular composition, viral tropism and response to infection. Ciliated cells are replication centres across ages, but infected paediatric cultures generate a distinct goblet inflammatory subtype with high interferon-stimulated gene expression and incomplete viral replication. In older adult cultures, infection increases basaloid-like cells that facilitate viral spread and are linked to altered epithelial repair. Integration with in vivo COVID-19 single-cell datasets confirms age-specific induction of these cell states, validating that the in vitro model recapitulates early epithelial responses to SARS-CoV-2.