Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, leads to respiratory symptoms that can be fatal. However, neurological symptoms have also been observed in some patients. The cause of these complications is currently unknown. Here, we use human-pluripotent-stem-cell-derived brain organoids to examine SARS-CoV-2 neurotropism. We find expression of viral receptor ACE2 in mature choroid plexus cells expressing abundant lipoproteins, but not in neurons or other cell types. We challenge organoids with SARS-CoV-2 spike pseudovirus and live virus to demonstrate viral tropism for choroid plexus epithelial cells but little to no infection of neurons or glia. We find that infected cells are apolipoprotein- and ACE2-expressing cells of the choroid plexus epithelial barrier. Finally, we show that infection with SARS-CoV-2 damages the choroid plexus epithelium, leading to leakage across this important barrier that normally prevents entry of pathogens, immune cells, and cytokines into cerebrospinal fluid and the brain.

2019 年冠状病毒病 (COVID-19) 由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 病毒引起，会导致致命的呼吸道症状。然而，在一些患者中也观察到神经系统症状。这些并发症的原因目前尚不清楚。在这里，我们使用人类多能干细胞来源的大脑类器官来检查 SARS-CoV-2 的神经趋向性。我们发现病毒受体 ACE2 在表达丰富脂蛋白的成熟脉络丛细胞中表达，但在神经元或其他细胞类型中不表达。我们用 SARS-CoV-2 刺突假病毒和活病毒挑战类器官，以证明病毒对脉络丛上皮细胞的趋向性，但对神经元或神经胶质细胞的感染很少或没有。我们发现受感染的细胞是脉络丛上皮屏障的载脂蛋白和 ACE2 表达细胞。最后，我们发现 SARS-CoV-2 感染会损害脉络丛上皮，导致这一重要屏障渗漏，而该屏障通常会阻止病原体、免疫细胞和细胞因子进入脑脊液和大脑。