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

Published version
Peer-reviewed

Repository DOI


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Authors

Woodall, Maximillian NJ 
Cujba, Ana-Maria 
Case, Katie-Marie 
Masonou, Tereza 

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.

Description

Funder: Microscopy was performed at the Light Microscopy Core Facility, UCL GOS Institute of Child Health supported by the NIHR GOSH BRC award 17DD08.


Funder: This project has been made possible in part by grants 2017-174169 and 2019-202654 from the Chan Zuckerberg Foundation and Sanger core grant WT206194.

Keywords

Humans, COVID-19, SARS-CoV-2, Angiotensin-Converting Enzyme 2, Adult, Middle Aged, Aged, Epithelial Cells, Serine Endopeptidases, Nasal Mucosa, Child, Age Factors, Virus Replication, Child, Preschool, Viral Tropism, Male, Female, Aged, 80 and over, Cells, Cultured, Adolescent, Infant

Journal Title

Nat Microbiol

Conference Name

Journal ISSN

2058-5276
2058-5276

Volume Title

9

Publisher

Springer Science and Business Media LLC
Sponsorship
European Commission Horizon 2020 (H2020) Societal Challenges (874656)