Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany.
Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Germany.
EMBO J. 2020 Oct 15;39(20):e106230. doi: 10.15252/embj.2020106230. Epub 2020 Sep 23.
COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Düsseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within 2 days of exposure. We identified that SARS-CoV-2 preferably targets neurons of brain organoids. Imaging neurons of organoids reveal that SARS-CoV-2 exposure is associated with altered distribution of Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Our studies, therefore, provide initial insights into the potential neurotoxic effect of SARS-CoV-2 and emphasize that brain organoids could model CNS pathologies of COVID-19.
由 SARS-CoV-2 感染引起的 COVID-19 大流行是一场公共卫生紧急事件。COVID-19 通常表现为呼吸道疾病。出乎意料的是，新出现的临床报告表明，神经症状持续上升，表明 SARS-CoV-2 对中枢神经系统 (CNS) 有不良影响。在这里，我们展示了一种杜塞尔多夫分离株的 SARS-CoV-2 在接触后 2 天内进入 3D 人脑类器官。我们发现 SARS-CoV-2 优先靶向脑类器官的神经元。对类器官神经元进行成像显示，SARS-CoV-2 暴露与 Tau 从轴突到胞体的分布改变、过度磷酸化和明显的神经元死亡有关。因此，我们的研究为 SARS-CoV-2 的潜在神经毒性作用提供了初步见解，并强调脑类器官可以模拟 COVID-19 的中枢神经系统疾病。
