Human Organoids as a Promising Platform for Fighting COVID-19

Abstract

The coronavirus disease 2019 (COVID-19) global pandemic evoked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a major public health problem with significant morbidity and mortality. Understanding the pathogenesis and molecular mechanisms underlying this novel virus is crucial for both fundamental research and clinical trials in order to devise effective therapies and vaccination regimens. Basic research on SARS-CoV-2 largely depends on ex vivo models that allow viral invasion and replication. Organoid models are now emerging as a valuable tool to investigate viral biology and disease progression, serving as an efficient platform to investigate potential therapies for COVID-19. Here, we summarize various human stem cell-derived organoid types employed in SARS-CoV-2 studies. We highlight key findings from these models, including cell tropisms and molecular mechanisms in viral infection. We also describe their use in identifying potential therapeutic agents against SARS-CoV-2. As more and more advanced organoids emerge, they will facilitate the understanding of disease pathogenesis for drug development in this dreaded pandemic.

Keywords: COVID-19; SARS-CoV-2; drug screening; infection; organoid.

Figure 1

Schematic representation of the main organs affected by SARS-COV-2. Besides lung injury caused by SARS-CoV-2, symptoms have also been noted in multiple other organs, including brain, eye, heart, liver, intestine, kidney, and blood vessels.

Figure 2

Common analyses and key applications of human PSC- and ASC-derived organoid platforms in COVID-19 research. Various organoids derived from PSCs or ASCs have been established to study SARS-CoV-2 infection. Organoid models are commonly used to investigate SARS-CoV-2 tropism and COVID-19 pathophysiology across different organs, as well as to verify the safety and efficacy of candidate drugs and screen new therapeutic strategies. Furthermore, patient-derived organoids may potentially serve as a platform to test the efficacy of antiviral drugs for individual patients.