Human pluripotent stem cell-based organoids and cell platforms for modelling SARS-CoV-2 infection and drug discovery

The coronavirus disease 2019 (COVID-19) global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected over 200 countries and territories worldwide and resulted in more than 2.5 million deaths. In a pressing search for treatments and vaccines, research models based on human stem cells are emerging as crucial tools to investigate SARS-CoV-2 infection mechanisms and cellular responses across different tissues. Here, we provide an overview of the variety of human pluripotent stem cell-based platforms adopted in SARS-CoV-2 research, comprising monolayer cultures and organoids, which model the multitude of affected tissues in vitro. We highlight the strengths of these platforms, including their application to assess both the susceptible cell types and the pathogenesis of SARS-CoV-2. We describe their use to identify drug candidates for further investigation in addition to discussing their limitations in fully recapitulating COVID-19 pathophysiology. Overall, stem cell models are facilitating the understanding of SARS-CoV-2 and prove to be versatile platforms for studying infections.