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Updated: May 11, 2026
Culturing of Human Nasal Epithelial Cells at the Air Liquid Interface
Published on: October 8, 2013
Age-specific nasal epithelial responses to SARS-CoV-2 infection
Maximillian N J Woodall1, Ana-Maria Cujba2, Kaylee B Worlock3
1Great Ormond Street UCL Institute of Child Health, London, UK.
Insights
SARS-CoV-2 infection impacts nasal cells differently across ages. Paediatric cells show inflammation, while older adults exhibit increased basaloid cells promoting viral spread, revealing age-specific cellular responses to COVID-19.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- SARS-CoV-2 infection severity varies significantly with age, with higher mortality in older adults.
- Understanding age-related differences in cellular response to SARS-CoV-2 is crucial for targeted interventions.
Purpose of the Study:
- To investigate age-specific differences in nasal epithelial cell responses to SARS-CoV-2 infection.
- To compare cellular tropism, gene expression (ACE2, TMPRSS2), and functional changes in paediatric, adult, and older adult nasal cells.
Main Methods:
- Ex vivo culture of nasal epithelial cells from paediatric, adult, and older adult donors.
- Infection of cultured cells with SARS-CoV-2.
- Analysis of cell tropism, ACE2/TMPRSS2 expression, and gene expression profiles (interferon-stimulated genes).
- Integration of data from in vivo COVID-19 studies.
Main Results:
- SARS-CoV-2 tropism and ACE2/TMPRSS2 expression vary by age group in nasal epithelial cells.
- Ciliated cells are viral replication sites in all age groups.
- Paediatric cultures develop a goblet inflammatory subtype with high interferon response and incomplete viral replication.
- Older adult cultures show increased basaloid-like cells, facilitating viral spread and altered epithelial repair.
Conclusions:
- Nasal epithelial cell responses to SARS-CoV-2 are age-dependent.
- Distinct cellular subtypes and pathways are implicated in paediatric and older adult COVID-19 pathogenesis.
- The in vitro model effectively recapitulates early epithelial responses to SARS-CoV-2, providing insights into age-related disease mechanisms.
Abstract:
Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in infected people over 85 years of age remains high. Here we investigate differences in the cellular landscape and function of paediatric (<12 years), adult (30-50 years) and older adult (>70 years) ex vivo cultured nasal epithelial cells in response to infection with SARS-CoV-2. We show that cell tropism of SARS-CoV-2, and expression of ACE2 and TMPRSS2 in nasal epithelial cell subtypes, differ between age groups. While ciliated cells are viral replication centres across all age groups, a distinct goblet inflammatory subtype emerges in infected paediatric cultures and shows high expression of interferon-stimulated genes and incomplete viral replication. In contrast, older adult cultures infected with SARS-CoV-2 show a proportional increase in basaloid-like cells, which facilitate viral spread and are associated with altered epithelial repair pathways. We confirm age-specific induction of these cell types by integrating data from in vivo COVID-19 studies and validate that our in vitro model recapitulates early epithelial responses to SARS-CoV-2 infection.
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