Catch me if you can: SARS-CoV-2 detection in brains of deceased patients with COVID-19.
Catch me if you can: SARS-CoV-2 detection in brains of deceased patients with COVID-19.
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DOI：
10.1016/s1474-4422(20)30371-9
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发表时间：
2020-11
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通讯作者：
Frank S
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作者：
Frank S
在美国传记犯罪电影《Catch Me If You Can》中，联邦调查局特工卡尔·汉拉蒂（Carl Hanratty）全力以赴地抓住臭名昭著的骗子和支票伪造者小弗兰克·阿巴戈内尔（Frank Abagnale Jr.）。Hanratty对罪魁祸首的不懈追求与目前COVID 19的研究工作有着惊人的相似之处，这些研究工作旨在寻找严重急性呼吸道综合征冠状病毒2（SARSCoV2）感染可能在大脑中留下变化的证据。在The Lancet Neurology中，Jakob Matschke及其同事1详细描述了CNS中与COVID 19相关的组织学变化。通过细致的检测工作，他们绘制了大脑对病毒感染的免疫炎症反应，并在COVID 19患者的大部分尸检大脑中检测到SARSCoV2蛋白表达。Matschke及其同事分析了来自一个大型队列的43名死于COVID 19的患者的大脑，2重点关注炎症变化和SARSCoV2的检测。为了找出哪些CNS细胞类型易于感染SARSCoV2，作者筛选了基因表达数据集，以获得与病毒进入和持续相关的特征。他们的计算机分析显示，血管紧张素转换酶2（ACE2）在少突胶质细胞中高锡永，跨膜丝氨酸蛋白酶2和4（TMPRSS 2和TMPRSS 4）在神经元中高表达，这些基因编码的蛋白质与SARS CoV 2宿主细胞进入（ACE2）和病毒装饰刺突的蛋白水解引发（TMPRSS 2）密切相关。有趣的是，2020年9月发表的一项使用人脑类器官的研究表明，SARSCoV2可以很容易地感染和杀死神经元。病毒感染引起的神经元细胞死亡之前是异常的神经元内定位和Tau蛋白的过度磷酸化，4类似于阿尔茨海默病和其他神经退行性疾病的发病机制。Matschke及其同事使用定量RTPCR（qRTPCR）和免疫组织化学方法检测SARSCoV2。48%的病例检测到病毒RNA，40%的病例检测到病毒蛋白。总的来说，作者在51%的被调查大脑中发现了SARSCoV2，病毒RNA或病毒蛋白（或两者兼而有之）。值得注意的是，SARSCoV2的存在与神经病理学改变的严重程度无关。而
In the American biographical crime film Catch Me If You Can, FBI agent Carl Hanratty goes all out to catch the notorious impostor and cheque counterfeiter Frank Abagnale Jr. Hanratty’s dogged pursuit of the culprit bears striking resemblance to current COVID19 research efforts to find evidence of changes that severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection might leave in the brain. In The Lancet Neurology, Jakob Matschke and colleagues1 give a detailed account of the histological alterations related to COVID19 in the CNS. Through meticulous detective work, they mapped the brain’s immunoinflammatory response to viral infection and detected SARSCoV2 protein expression in a substantial percentage of autoptic brains of patients with COVID19. Matschke and colleagues analysed 43 brains from a large cohort of patients who died with COVID19, 2 focusing on inflammatory changes and detection of SARSCoV2. To find out which CNS cell types are prone to SARSCoV2 infection, the authors screened gene expression datasets for signatures related to viral entry and persistence. Their insilico analysis showed high expres sion of angiotensinconverting enzyme 2 (ACE2) in oligodendrocytes and of transmembrane serine pro teases 2 and 4 (TMPRSS2 and TMPRSS4) in neurons—genes that code for proteins crucially implicated in SARS CoV2 hostcell entry (ACE2) and proteolytic priming of the virusdecorating spikes (TMPRSS2). 3 Interestingly, a study using human brain organoids, published in September, 2020, 4 showed that SARSCoV2 can readily infect and kill neurons. The neuronal cell death upon viral infec tion was preceded by aberrant intraneuronal localisa tion and hyperphosphorylation of Tau protein, 4 similar to the pathogenesis of Alzheimer’s disease and other neuro degenerative diseases.Matschke and colleagues used quantitative RTPCR (qRTPCR) and immunohistochemistry with antibodies against nucleocapsid and spike proteins to detect SARSCoV2. Whereas viral RNA was detected in 48% of cases, viral protein detection was positive in 40%. Overall, the authors found SARSCoV2, either viral RNA or viral protein (or both), in 51% of the brains investi gated. Remarkably, SARSCoV2 presence did not correlate with the severity of neuropathological alterations. While the