Neurological complications are common in patients with COVID-19. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal pathogen of COVID-19, has been detected in some patient brains, its ability to infect brain cells and impact their function is not well understood. Here, we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies.

神经系统并发症在 COVID-19 患者中很常见。尽管在一些患者大脑中检测到了 COVID-19 的致病病原体——严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2)，但其感染脑细胞并影响脑细胞功能的能力尚不清楚。在这里，我们研究了人类诱导多能干细胞 (hiPSC) 衍生的单层脑细胞和区域特异性脑类器官对 SARS-CoV-2 感染的敏感性。我们发现神经元和星形胶质细胞被稀疏感染，但脉络丛上皮细胞受到强烈感染。我们优化了从 hiPSC 生成脉络丛类器官的方案，并表明这些类器官的高效 SARS-CoV-2 感染与细胞死亡增加和转录失调有关，表明炎症反应和细胞功能缺陷。总之，我们的研究结果为选择性 SARS-CoV-2 向神经性提供了证据，并支持使用 hiPSC 衍生的脑类器官作为平台来研究脑细胞的 SARS-CoV-2 感染易感性、病毒引起的脑功能障碍的机制和治疗策略。