论文
论文标题：Dysregulation of brain and choroid plexus cell types in severe COVID-19
作者：Andrew C. Yang, Fabian Kern, Patricia M. Losada, Maayan R. Agam, Christina A. Maat, Georges P. Schmartz, Tobias Fehlmann, Julian A. Stein, Nicholas Schaum, Davis P. Lee, Kruti Calcuttawala, Ryan T. Vest, Daniela Berdnik, Nannan Lu, Oliver Hahn, David Gate, M. Windy McNerney, Divya Channappa, Inma Cobos, Nicole Ludwig, Walter J. Schulz-Schaeffer, Andreas Keller, Tony Wyss-Coray
期刊：Nature
发表时间：2021/06/21
数字识别码：10.1038/s41586-021-03710-0
摘要：Though SARS-CoV-2 primarily targets the respiratory system, patients and survivors can suffer neurological symptoms1–3. Yet, an unbiased understanding of the cellular and molecular processes affected in the brains of COVID-19 patients is still missing. Here, we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control (including 1 terminal influenza) and 8 COVID-19 patients. While a systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations which predict that choroid plexus barrier cells sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. We discover COVID-19 disease-associated microglia and astrocyte subpopulations that share features with pathological cell states reported in human neurodegenerative disease4–6. Synaptic signaling of upper-layer excitatory neurons—evolutionarily expanded in humans7 and linked to cognitive function8—are preferentially affected in COVID-19. Across cell types, COVID-19 perturbations overlap with those in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia, and depression. Our findings and public dataset provide a molecular framework to understand COVID-19 related neurological disease observed now and which may emerge later.
新冠患者特别是重症患者会出现多种神经或精神疾病的症状，且可能在新冠痊愈后持续存在。为理解其中的机制，美国斯坦福大学医学院（Stanford School of Medicine）和德国萨尔大学（Saarland University）合作团队通过分子生物学的方法，对 8 名重症新冠死亡患者和 14 名其他原因死亡患者的新鲜冷冻脑组织的特定细胞类型进行单细胞转录组测序和综合评估，分析了 65309 个单细胞转录组中的数千个基因。结果表明，死于新冠的患者大脑存在明显的炎症及神经通路受损，与死于阿尔茨海默病、帕金森病等神经退行性疾病的患者的大脑情况非常相似，且与认知、精神分裂症和抑郁症相关的基因在新冠患者的大脑中更频繁地被激活。但该研究没有在大脑中发现新冠病毒的分子痕迹，表明病毒在身体其他部位的感染就可能足以引起神经系统症状。该研究已公开原始测序数据，为进一步剖析新冠病毒对大脑影响的分子机制提供资源。相关论文 6 月 21 日发表于《自然》（Nature）。（Stanford School of Medicine，Nature）
