Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19
Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19
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DOI：
10.1038/s41593-020-00758-5
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发表时间：
2020-11-30
影响因子：
25
通讯作者：
Heppner, Frank L.
中科院分区：
文献类型：
--
作者：
Meinhardt, Jenny;Radke, Josefine;Heppner, Frank L.
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、内皮和神经组织的紧密邻近，包括脆弱的嗅觉和感觉神经末梢。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，包括延髓的主要呼吸和心血管控制中心。作者证明了 SARS-CoV-2 在鼻咽和大脑中的存在，表明该病毒存在于中枢神经系统中，并可能通过嗅粘膜进入，利用嗅粘膜、内皮和神经组织的紧密邻近区域。
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.The authors demonstrate the presence of SARS-CoV-2 in the nasopharynx and brain, suggesting that the virus is present in the CNS and may enter through the olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue.