Endocrine in vitro models to study pathophysiology and diabetes in SARS-CoV-2/COVID-19

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Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is known to infect mostly the respiratory tract but also causes direct injury in kidneys, heart, brain, and gastrointestinal organs. Furthermore, SARS-CoV-2 appears to directly compromise the insulin metabolism infection while the course of coronavirus disease 2019 (COVID-19) itself is impacted by diabetes mellitus. So far, it is unclear whether SARS-CoV-2 selectively targets and infects beta-cells and affects their function and if so, in which way. Moreover, cellular response mechanisms towards SARS-CoV-2 infection might differ across various organs. Preliminary data from our labs show that human islets of Langerhans lacking sufficient quality for transplantation can be productively infected with SARS-CoV-2. However, such transplantation-incompetent islets have limited availability, are very expensive and often render with low preparation quality and purity. Moreover, donor diversity and restricted material requires multiple islet preparations to generate robust results. Therefore, the overall aim of this project is to employ stem cell-derived pancreatic endocrine cells as model system to investigate SARS-CoV-2 infection and replication in order to understand the diabetes pathogenesis in COVID-19 patients.