Human organoid models to study coronavirus infections of the respiratory tract

The coronavirus disease 2019 (COVID-19) pandemic emphasized the need to study coronaviruses more thoroughly. Next to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), humans can be infected by SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), and various seasonal coronaviruses. It is likely that all human coronaviruses have a zoonotic origin and circulated in animal reservoirs before crossing the species barrier into humans. Historically, these viruses have been investigated in vitro and in vivo, mainly utilizing immortalized cell lines and animal models, respectively. Recently, more advanced physiological model systems have been developed to study coronavirus host interactions, with human organoids serving as innovative in vitro tissue culture system that closely mimics human physiology. Organoids provide a promising platform for investigating coronavirus infections, exploring viral tropism, studying host immune responses, and evaluating potential therapeutic interventions. This review explores the origins and use of airway organoids in studying coronaviruses. Additionally, it outlines prospects for leveraging airway organoids for examination of both innate and adaptive immune responses, evaluation of antiviral drugs, and creating intricate co-culture models for enhanced insight into coronavirus infections of the respiratory tract.