Since the global outbreak of SARS-CoV-2 (COVID-19), infections of diverse human organs along with multiple symptoms continue to be reported. However, the susceptibility of the brain to SARS-CoV-2, and the mechanisms underlying neurological infection are still elusive. Here, we utilized human embryonic stem cell-derived brain organoids and monolayer cortical neurons to investigate infection of brain with pseudotyped SARS-CoV-2 viral particles. Spike-containing SARS-CoV-2 pseudovirus infected neural layers within brain organoids. The expression of ACE2, a host cell receptor for SARS-CoV-2, was sustained during the development of brain organoids, especially in the somas of mature neurons, while remaining rare in neural stem cells. However, pseudotyped SARS-CoV-2 was observed in the axon of neurons, which lack ACE2. Neural infectivity of SARS-CoV-2 pseudovirus did not increase in proportion to viral load, but only 10% of neurons were infected. Our findings demonstrate that brain organoids provide a useful model for investigating SARS-CoV-2 entry into the human brain and elucidating the susceptibility of the brain to SARS-CoV-2.

中文翻译：

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SARS-CoV-2伪病毒感染脑器官和2D皮质神经元。

自从全球爆发SARS-CoV-2（COVID-19）以来，继续报道了多种人体器官的感染以及多种症状。但是，大脑对SARS-CoV-2的敏感性以及潜在的神经感染机制仍然难以捉摸。在这里，我们利用人类胚胎干细胞衍生的大脑类器官和单层皮质神经元来研究假型SARS-CoV-2病毒颗粒对大脑的感染。含有尖峰的SARS-CoV-2伪病毒感染了大脑类器官内的神经层。ACE2是SARS-CoV-2的宿主细胞受体，在脑类器官形成过程中（尤其是在成熟神经元的体细胞中）持续表达，而在神经干细胞中仍然很少见。但是，在缺少ACE2的神经元轴突中观察到假型SARS-CoV-2。SARS-CoV-2伪病毒的神经感染性并未随病毒载量的增加而增加，但仅感染了10％的神经元。我们的研究结果表明，大脑类器官为研究SARS-CoV-2进入人脑并阐明大脑对SARS-CoV-2的敏感性提供了有用的模型。