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.

Maximillian N. J. Woodall, Ana-Maria Cujba, Kaylee B. Worlock, Katie-Marie Case, Tereza Masonou, Masahiro Yoshida, Krzysztof Polanski, Ni Huang, Rik G. H. Lindeboom, Lira Mamanova, Liam Bolt, Laura Richardson, Batuhan Cakir, Samuel Ellis, Machaela Palor, Thomas Burgoyne, Andreia Pinto, Dale Moulding, Timothy D. McHugh, Aarash Saleh, Eliz Kilich, Puja Mehta, Chris O'Callaghan, Jie Zhou, Wendy Barclay, Paolo De Coppi, Colin R. Butler, Mario Cortina-Borja, Heloise Vinette, Sunando Roy, Judith Breuer, Rachel C. Chambers, Wendy E. Heywood, Kevin Mills, Robert E. Hynds, Sarah A. Teichmann, Kerstin B. Meyer, Marko Z. Nikolić, Claire M. Smith