tetano
Editor, Senior Moderator
iScience
. 2025 Feb 12;28(3):111999.
doi: 10.1016/j.isci.2025.111999. eCollection 2025 Mar 21. Divergent responses to SARS-CoV-2 infection in bronchial epithelium with pre-existing respiratory diseases
Justine Oliva[SUP] 1 [/SUP], Manon Ruffin[SUP] 2 [/SUP], Claire Calmel[SUP] 2 [/SUP], Aurélien Gibeaud[SUP] 1 [/SUP], Andrés Pizzorno[SUP] 1 3 4 [/SUP], Clémence Gaudin[SUP] 2 [/SUP], Solenne Chardonnet[SUP] 5 [/SUP], Viviane de Almeida Bastos[SUP] 5 [/SUP], Manuel Rosa-Calatrava[SUP] 1 3 4 6 [/SUP], Antoine Soulé[SUP] 7 [/SUP], Amin Emad[SUP] 7 8 [/SUP], Simon Rousseau[SUP] 9 [/SUP], Harriet Corvol[SUP] 2 10 [/SUP], Olivier Terrier[SUP] 1 [/SUP], Loïc Guillot[SUP] 2 [/SUP]
Affiliations
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.
Keywords: Microbiology; Respiratory medicine; Virology.
. 2025 Feb 12;28(3):111999.
doi: 10.1016/j.isci.2025.111999. eCollection 2025 Mar 21. Divergent responses to SARS-CoV-2 infection in bronchial epithelium with pre-existing respiratory diseases
Justine Oliva[SUP] 1 [/SUP], Manon Ruffin[SUP] 2 [/SUP], Claire Calmel[SUP] 2 [/SUP], Aurélien Gibeaud[SUP] 1 [/SUP], Andrés Pizzorno[SUP] 1 3 4 [/SUP], Clémence Gaudin[SUP] 2 [/SUP], Solenne Chardonnet[SUP] 5 [/SUP], Viviane de Almeida Bastos[SUP] 5 [/SUP], Manuel Rosa-Calatrava[SUP] 1 3 4 6 [/SUP], Antoine Soulé[SUP] 7 [/SUP], Amin Emad[SUP] 7 8 [/SUP], Simon Rousseau[SUP] 9 [/SUP], Harriet Corvol[SUP] 2 10 [/SUP], Olivier Terrier[SUP] 1 [/SUP], Loïc Guillot[SUP] 2 [/SUP]
Affiliations
- PMID: 40104058
- PMCID: PMC11914195
- DOI: 10.1016/j.isci.2025.111999
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.
Keywords: Microbiology; Respiratory medicine; Virology.