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Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19
Nature Neuroscience ( IF 21.2 ) Pub Date : 2020-11-30 , DOI: 10.1038/s41593-020-00758-5
Jenny Meinhardt 1 , Josefine Radke 1, 2, 3 , Carsten Dittmayer 1 , Jonas Franz 4, 5, 6 , Carolina Thomas 4, 6 , Ronja Mothes 1 , Michael Laue 7 , Julia Schneider 8 , Sebastian Brünink 8 , Selina Greuel 9 , Malte Lehmann 10 , Olga Hassan 1 , Tom Aschman 1 , Elisa Schumann 1, 3 , Robert Lorenz Chua 11 , Christian Conrad 11 , Roland Eils 11, 12 , Werner Stenzel 1 , Marc Windgassen 13 , Larissa Rößler 13 , Hans-Hilmar Goebel 1 , Hans R Gelderblom 7 , Hubert Martin 1 , Andreas Nitsche 7 , Walter J Schulz-Schaeffer 14 , Samy Hakroush 15 , Martin S Winkler 16 , Björn Tampe 17 , Franziska Scheibe 18, 19 , Péter Körtvélyessy 18, 20 , Dirk Reinhold 21 , Britta Siegmund 10 , Anja A Kühl 22 , Sefer Elezkurtaj 9 , David Horst 9 , Lars Oesterhelweg 13 , Michael Tsokos 13 , Barbara Ingold-Heppner 23 , Christine Stadelmann 4 , Christian Drosten 8 , Victor Max Corman 8 , Helena Radbruch 1 , Frank L Heppner 1, 2, 19, 24
Affiliation  

The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural–mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.



中文翻译:

嗅觉跨粘膜 SARS-CoV-2 入侵作为 COVID-19 个体中枢神经系统进入的端口

新发现的严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 会导致大流行性呼吸道疾病 COVID-19。此外,还描述了全身(包括中枢神经系统)的血栓栓塞事件。鉴于在大多数 COVID-19 患者中观察到的神经系统症状,中枢神经系统很可能存在 SARS-CoV-2 外显。通过各种方式,我们证明了鼻咽和大脑的解剖学不同区域中存在 SARS-CoV-2 RNA 和蛋白质。此外,我们描述了与中枢神经系统血栓栓塞性缺血性梗塞等感染相关的形态学变化,并提供了 SARS-CoV-2 向神经性的证据。SARS-CoV-2 可以通过嗅粘膜中的神经粘膜界面进入神经系统,利用嗅粘膜、内皮和神经组织(包括脆弱的嗅觉和感觉神经末梢)的邻近区域。随后,SARS-CoV-2 似乎遵循神经解剖结构,穿透定义的神经解剖区域,包括延髓中的主要呼吸和心血管控制中心。

更新日期:2020-12-01
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