Dysregulation of brain and choroid plexus cell types in severe COVID-19.
Dysregulation of brain and choroid plexus cell types in severe COVID-19.
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DOI：
10.1038/s41586-021-03710-0
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发表时间：
2021-07
期刊：
影响因子：
64.8
通讯作者：
Wyss-Coray T
中科院分区：
文献类型：
--
作者：
Yang AC;Kern F;Losada PM;Agam MR;Maat CA;Schmartz GP;Fehlmann T;Stein JA;Schaum N;Lee DP;Calcuttawala K;Vest RT;Berdnik D;Lu N;Hahn O;Gate D;McNerney MW;Channappa D;Cobos I;Ludwig N;Schulz-Schaeffer WJ;Keller A;Wyss-Coray T
虽然SARS-CoV-2主要针对呼吸系统，但COVID-19患者和幸存者可能会出现神经系统症状。然而，对COVID-19患者大脑中受影响的细胞和分子过程缺乏公正的理解。在这里，我们分析了来自14名对照个体（包括1名晚期流感患者）和8名COVID-19患者的30个额叶皮层和脉络丛样本的65，309个单核转录组。虽然我们的系统分析没有在大脑中产生SARS-CoV-2的分子痕迹，但我们观察到广泛的细胞扰动，表明脉络丛的屏障细胞感知并将外周炎症传递到大脑中，并显示外周T细胞浸润脑实质。我们发现了与COVID-19相关的小胶质细胞和星形胶质细胞亚群，它们与先前在人类神经退行性疾病中报道的病理细胞状态具有共同特征。上层兴奋性神经元的突触信号传导-在人类中进化扩展并与认知功能相关-在COVID-19中优先受到影响。在所有细胞类型中，与COVID-19相关的扰动与慢性脑部疾病中发现的扰动重叠，并存在于与认知、精神分裂症和抑郁症相关的遗传变异中。我们的研究结果和公开数据集提供了一个分子框架，以了解目前对COVID-19相关神经系统疾病的观察，以及任何可能在以后出现的此类疾病。
Although SARS-CoV-2 primarily targets the respiratory system, patients with and survivors of COVID-19 can suffer neurological symptoms. However, an unbiased understanding of the cellular and molecular processes that are affected in the brains of patients with COVID-19 is missing. Here we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control individuals (including 1 patient with terminal influenza) and 8 patients with COVID-19. Although our systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations indicating that barrier cells of the choroid plexus sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. We discover microglia and astrocyte subpopulations associated with COVID-19 that share features with pathological cell states that have previously been reported in human neurodegenerative disease. Synaptic signalling of upper-layer excitatory neurons–which are evolutionarily expanded in humans and linked to cognitive function–is preferentially affected in COVID-19. Across cell types, perturbations associated with COVID-19 overlap with those found 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 current observations of COVID-19-related neurological disease, and any such disease that may emerge at a later date.
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影响因子：
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作者：
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Schlesner, Matthias
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