Cell response analysis in SARS-CoV-2 infected bronchial organoids

Bronchial organoids (BO) and BO-derived air-liquid interface models (BO-ALI) are used to model SARS-CoV-2 infection of human bronchial epithelial cells, reporting that ciliated cells were permissive to the virus, unlike basal cells. The development of an in vitro cell model that can be used to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research is expected. Here we conducted infection experiments in bronchial organoids (BO) and an BO-derived air-liquid interface model (BO-ALI) using 8 SARS-CoV-2 variants. The infection efficiency in BO-ALI was more than 1,000 times higher than that in BO. Among the bronchial epithelial cells, we found that ciliated cells were infected with the virus, but basal cells were not. Ciliated cells died 7 days after the viral infection, but basal cells survived after the viral infection and differentiated into ciliated cells. Fibroblast growth factor 10 signaling was essential for this differentiation. These results indicate that BO and BO-ALI may be used not only to evaluate the cell response to SARS-CoV-2 and coronavirus disease 2019 (COVID-19) therapeutic agents, but also for airway regeneration studies.

Automated summary

Bronchial organoids (BO) and BO-derived air-liquid interface models (BO-ALI) can be used to model and study SARS-CoV-2 infection mechanisms and therapeutic methods. Ciliated cells are susceptible to virus infection, while basal cells are not. These models can also be used for airway regeneration studies.