MERS-CoV and SARS-CoV-2 infection in diverse human lung organoid-derived cultures

The COVID-19 pandemic heralded the upsurge in human-derived lung organoid-based studies due to their cellular heterogeneity that partly emulates the cellular complexity of the respiratory tract. A major disadvantage of organoid models resides in their apical-in conformation that "hides" cells and proteins that are typically exposed to the air-liquid interface (ALI) in the airways and are targets of viruses. Here, we generated monolayers and ALI cultures to facilitate cell exposure to highly relevant pathogens and compared them to parental organoids. Organoids at the ALI captured infection and immune responses better than organoids and organoid-derived monolayer cultures. Organoids at the ALI are a viable approach to improve identification and characterization of virus infection, host responses, and therapeutic testing.