SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. Recent clinical studies show a strong association with COVID-19 and diabetes. We find that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and adult hepatocyte and cholangiocyte organoids. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection and for disease modeling of COVID-19.

SARS-CoV-2 引起了 COVID-19 大流行。迫切需要利用人类疾病相关细胞研究 SARS-CoV-2 感染的生理模型。 COVID-19 病理生理学包括呼吸衰竭，但也涉及其他器官系统，包括肠道、肝脏、心脏和胰腺。我们提出了一个由人类多能干细胞（hPSC）的细胞和类器官衍生物组成的实验平台。具有刺突的假进入病毒感染胰腺内分泌细胞、肝类器官、心肌细胞和多巴胺能神经元。最近的临床研究表明，与 COVID-19 和糖尿病密切相关。我们发现人类胰腺 β 细胞和肝脏类器官对 SARS-CoV-2 感染高度敏感，并使用成人原代人类胰岛以及成人肝细胞和胆管细胞类器官进行了进一步验证。 SARS-CoV-2 感染引起趋化因子的显着表达，这在人类 COVID-19 肺部尸检样本中也可见到。 hPSC 衍生的细胞/类器官为了解人体组织对 SARS-CoV-2 感染的细胞反应和 COVID-19 疾病建模提供了有价值的模型。