SARS-CoV-2 & COPD: Inflammasome & Innate Immune Gene Expression & Protein Secretion

Airway Models Reveal Innate Immune Response to SARS-CoV-2

Researchers have utilized human induced pluripotent stem cell (iPSC)-derived airway models to analyze the response to SARS-CoV-2 infection in both healthy and chronic obstructive pulmonary disease (COPD) bronchial epithelium. The study, published January 23, 2026, in iScience, details the cellular gene expression and protein secretion related to inflammasome and innate immune responses during infection.

The research team, led by Lisa Morichon at the CEMIPAI: Centre d’Etudes des Maladies Infectieuses et Pharmacologie Anti-Infectieuses, CNRS UAR3725, in Montpellier, France, found that SARS-CoV-2 successfully infected the iPSC-derived airway models, impacting the airway epithelium in ways consistent with previous observations. These impacts included cell shedding, cilia disruption, and mucus secretion. The early innate immune response observed mirrored results from primary organoid studies.

A key aspect of the study involved analyzing gene expression levels of various innate immune response genes – including CXCL10, IL6, IFI27, and OAS1 – in non-infected and infected samples from healthy and COPD iALI models over 18 days post-infection. Data was presented as differences from the log2 relative gene expression to GAPDH gene median, using a color scale to represent expression levels. Integrity of the tissue was assessed using ITGB1 and GJA1 relative gene expression.

Venn diagrams were used to illustrate significantly overexpressed genes in infected samples compared to non-infected samples at 1, 4, and 11 days post-infection. The analysis revealed differences in gene expression patterns between healthy and COPD models.

Protein secretion analysis, conducted at 4 days post-infection, focused on key cytokine storm effectors associated with COVID-19, including IL-6, CCL2, G-CSF, CCL5, IL-2, IL-7, CXCL8, TNFα, CXCL10, and IL-10. Results were presented as a heatmap, showing deviations from the median of log2-transformed protein concentrations normalized to total protein. Specific analysis of CCL5 (RANTES), G-CSF, CXCL10, and IL-2 protein concentrations showed statistically significant differences between healthy and COPD iALI models.

The study highlights the importance of understanding the innate immune response to SARS-CoV-2, a topic also addressed in a review published in Inflammation in August 2022. That review focused on the innate immune response to SARS-CoV-2 and the virus’s ability to evade the immune system. Research also indicates the role of IL-1 family cytokines in inflammation and immunity, as reported by Nature.

Further research, including a study published in the American Journal of Respiratory and Critical Care Medicine in May 2022, has demonstrated increased SARS-CoV-2 infection, protease activity, and inflammatory responses in COPD primary bronchial epithelial cells, as defined through single-cell RNA sequencing. This suggests that individuals with pre-existing lung conditions may experience a heightened inflammatory response to the virus.

The iPSC-derived airway models provide a valuable tool for comparative analysis of SARS-CoV-2 infection, offering insights into the complex interplay between the virus and the host’s immune system. The findings contribute to a growing body of knowledge aimed at developing more effective strategies for preventing and treating COVID-19, particularly in vulnerable populations like those with COPD.