Action of SARS CoV2 in Human Brain Cultures

项目总结 有新的证据表明，SARS-CoV2或COVID19进入人类脑细胞导致 神经系统症状的后遗症。有人担心SARS-CoV2可能会导致神经毒性， 大脑中控制呼吸和心脏功能的区域的神经元死亡可能是原因之一 导致心肺功能急性丧失和死亡的因素。SARS-CoV2可以通过以下方式进入大脑 几种途径，包括通过鼻子，或神经细胞支配感染的肺组织，或通过细胞衬里 大脑中的毛细血管。新冠肺炎患者常在发病前丧失嗅觉或味觉 呼吸道症状和一名在SARS检测呈阳性之前出现格林-巴利综合征的患者- CoV2。看来，至少36%的COVID19患者有包括头痛在内的神经系统症状， 恶心、意识丧失、中风、神志不清、脑炎、脑膜炎和癫痫。这些临床 观察有力地表明了SARS-CoV2在神经元死亡中的作用，更重要的是大脑可能 第一批被感染和感染的组织之一。SARS-CoV2对大脑不同细胞的作用，如 以及脑细胞的感染性、趋向性和复制尚不清楚。在本申请中，我们建议 评估：(1)SARS-CoV2在人小胶质细胞、星形胶质细胞、神经元和 确定相对易感性？(2)细胞损伤的机制和评估潜在的保护 接近了。(3)检测人类神经元对SARS CoV2感染的转录反应， 单细胞水平的星形胶质细胞和小胶质细胞，以获得对脑细胞差异反应的新见解 SARS CoV2，以更好地了解病毒造成的神经缺陷。

PROJECT SUMMARY There is emerging evidence that SARS-CoV2 or COVID19 gains entry into human brain cells leading to a sequela of neurologic symptoms. There is concern that SARS-CoV2 may lead to neurotoxicity and that neuronal death in the regions of the brain that control respiration and cardiac function may be a contributing factor to the acute loss of cardio respiratory function and death. SARS-CoV2 could gain access to the brain by several routes including through the nose, or neurons innervating infected lung tissue or through the cells lining blood capillaries in the brain. COVID-19 patients lose their sense of smell or taste often before the onset of respiratory symptoms and a patient presented with Guillain-Barré syndrome before testing positive for SARS- CoV2. It appears that at least 36% of COVID19 patients had neurologic manifestations including headache, nausea, loss of consciousness, strokes, confusion, encephalitis, meningitis and seizures. These clinical observations strongly indicate a role for SARS-CoV2 in the death of neurons and importantly the brain may be one of the first tissues infected and affected. The actions of SARS-CoV2 on the different cells in the brain, as well as the infectivity, tropism, and replication in brain cells is not yet known. In this application we propose to evaluate: (1) The tropism and replication of SARS-CoV2 in human microglia, astrocytes, neurons, and determine relative susceptibility? (2) The mechanisms of cellular injury and evaluate potential protective approaches. (3) Determine the transcriptional responses to SARS CoV2 infection in human neurons, astrocytes, and microglia at the single cell level to gain new insight into the differential response of brain cells to SARS CoV2 to better understand the neural deficits the virus causes.