Human iPSC-derived airway models enable comparative analysis of SARS-CoV-2 infection in healthy and COPD bronchial epithelium

Lisa Morichon; Jitendriya Swain; Nathalie Gros; Amel Nasri; Florent Foisset; Gaetan Galisot; Victor Racine; Said Assou; Arnaud Bourdin; John De Vos; Delphine Muriaux

doi:10.1016/j.isci.2026.114741

Human iPSC-derived airway models enable comparative analysis of SARS-CoV-2 infection in healthy and COPD bronchial epithelium

iScience. 2026 Jan 23;29(3):114741. doi: 10.1016/j.isci.2026.114741. eCollection 2026 Mar 20.

Authors

Lisa Morichon^{1

2}, Jitendriya Swain^{1

3}, Nathalie Gros¹, Amel Nasri², Florent Foisset², Gaetan Galisot⁴, Victor Racine⁴, Said Assou², Arnaud Bourdin^{5

6}, John De Vos², Delphine Muriaux^{1

3}

Affiliations

¹ CEMIPAI: Centre d'Etudes des Maladies Infectieuses et Pharmacologie Anti-Infectieuses, CNRS UAR3725, 34293 Montpellier, France.
² Institute for Regenerative Medicine and Biotherapy (IRMB), University of Montpellier, INSERM, CHU Montpellier, 34295 Montpellier, France.
³ Institute of Research in Infectiology in Montpellier (IRIM), UMR 9004, CNRS & Université de Montpellier, 34293 Montpellier, France.
⁴ QuantaCell, IRMB, CHU Montpellier, 34295 Montpellier, France.
⁵ Department of Respiratory Diseases, CHU Montpellier, Arnaud de Villeneuve Hospital, INSERM, Montpellier 34000, France.
⁶ PhyMedExp INSERM 1046, University of Montpellier, 34000 Montpellier, France.

Abstract

SARS-CoV-2 causes severe and persistent lower respiratory tract infections, yet human models that recapitulate long-term tissue responses are limited. Here, we used a human induced pluripotent stem cell (hiPSC)-derived bronchial airway models (iALI) to investigate SARS-CoV-2 infection in healthy and COPD-derived tissues. Infection of iALI led to robust viral replication, persistent infection, cilia loss in infected ciliated epithelial cells, increased mucus secretion, and higher inflammatory cytokine release in COPD iALI. Notably, healthy iALI displayed a delayed innate immune response, whereas COPD iALI exhibited an earlier and stronger response, characterized by elevated IL-2, CCL5, G-CSF, and CXCL10 secretion, along with reduced sensitivity to antiviral treatment. These findings reveal donor-specific differences in bronchial epithelial responses to SARS-CoV-2 and establish iALI culture models as a powerful platform for studying long-term respiratory viral infections in both healthy and diseased contexts, especially COPD.

Keywords: Immunology; Infection control in health technology; Stem cells research; Virology.