Divergent responses to SARS-CoV-2 infection in bronchial epithelium with pre-existing respiratory diseases

Divergent responses to SARS-CoV-2 infection in bronchial epithelium with pre-existing respiratory diseases

Summary: Pre-existing respiratory diseases may influence coronavirus disease (COVID-19) susceptibility and severity. However, the molecular mechanisms underlying the airway epithelial response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection severity in patients with chronic...

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Main Authors: Justine Oliva, Manon Ruffin, Claire Calmel, Aurélien Gibeaud, Andrés Pizzorno, Clémence Gaudin, Solenne Chardonnet, Viviane de Almeida Bastos, Manuel Rosa-Calatrava, Antoine Soulé, Amin Emad, Simon Rousseau, Harriet Corvol, Olivier Terrier, Loïc Guillot
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:iScience
Subjects:
Virology
Respiratory medicine
Microbiology
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225002597
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Summary:Summary: Pre-existing respiratory diseases may influence coronavirus disease (COVID-19) susceptibility and severity. However, the molecular mechanisms underlying the airway epithelial response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection severity in patients with chronic respiratory diseases remain unelucidated. Using an in vitro model of differentiated primary bronchial epithelial cells, we aimed to investigate the molecular mechanisms of SARS-CoV-2 infection in pre-existing cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Our study revealed reduced susceptibility of CF and COPD airway epithelia to SARS-CoV-2, relative to that in healthy controls. Mechanistically, reduced transmembrane serine protease 2 (TMPRSS2) activity potentially contributed to this resistance of CF epithelium. Upregulated complement and inflammatory pathways in CF and COPD epithelia potentially primed the antiviral state prior to infection. Analysis of a COVID-19 patient cohort validated our findings, correlating specific inflammatory markers (IP-10, SERPINA1, and CFB) with COVID-19 severity. This study elucidates SARS-CoV-2 pathogenesis and identifies potential biomarkers for clinical monitoring.
ISSN:2589-0042

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