Age-specific nasal epithelial responses to SARS-CoV-2 infection.
Maximillian N J WoodallAna-Maria CujbaKaylee B WorlockKatie-Marie CaseTereza MasonouMasahiro YoshidaKrzysztof PolańskiNi HuangRik G H LindeboomLira MamanovaLiam BoltLaura RichardsonBatuhan CakirSamuel EllisMachaela PalorThomas BurgoyneAndreia Lucia PintoDale A MouldingTimothy D McHughAarash SalehEliz KilichPuja MehtaChris O'CallaghanJie ZhouWendy BarclayPaolo de CoppiColin R ButlerMario Cortina-BorjaHeloise VinetteSunando RoyJudith BreuerRachel Clare ChambersWendy E HeywoodKevin MillsRobert E HyndsSarah A TeichmannKerstin B MeyerMarko Z NikolićClaire Mary SmithPublished in: Nature microbiology (2024)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- single cell
- poor prognosis
- emergency department
- intensive care unit
- respiratory failure
- physical activity
- cell therapy
- magnetic resonance
- induced apoptosis
- chronic rhinosinusitis
- coronavirus disease
- young adults
- gene expression
- extracorporeal membrane oxygenation
- magnetic resonance imaging
- binding protein
- signaling pathway
- dna methylation
- cell proliferation
- big data
- community dwelling
- mechanical ventilation
- endoplasmic reticulum stress
- bone marrow
- cell cycle arrest
- contrast enhanced