Department of Histology and Embryology, College of Basic Medical Sciences, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, China.
Laboratory Teaching Center of Basic Medicine, Norman Bethune Health Science Center of Jilin University, Jilin Province, China.
J Med Virol. 2021 Mar;93(3):1304-1313. doi: 10.1002/jmv.26570. Epub 2020 Oct 14.
The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a significant and urgent threat to global health. This review provided strong support for central nervous system (CNS) infection with SARS-CoV-2 and shed light on the neurological mechanism underlying the lethality of SARS-CoV-2 infection. Among the published data, only 1.28% COVID-19 patients who underwent cerebrospinal fluid (CSF) tests were positive for SARS-CoV-2 in CSF. However, this does not mean the absence of CNS infection in most COVID-19 patients because postmortem studies revealed that some patients with CNS infection showed negative results in CSF tests for SARS-CoV-2. Among 20 neuropathological studies reported so far, SARS-CoV-2 was detected in the brain of 58 cases in nine studies, and three studies have provided sufficient details on the CNS infection in COVID-19 patients. Almost all in vitro and in vivo experiments support the neuroinvasive potential of SARS-CoV-2. In infected animals, SARS-CoV-2 was found within neurons in different brain areas with a wide spectrum of neuropathology, consistent with the reported clinical symptoms in COVID-19 patients. Several lines of evidence indicate that SARS-CoV-2 used the hematopoietic route to enter the CNS. But more evidence supports the trans-neuronal hypothesis. SARS-CoV-2 has been found to invade the brain via the olfactory, gustatory, and trigeminal pathways, especially at the early stage of infection. Severe COVID-19 patients with neurological deficits are at a higher risk of mortality, and only the infected animals showing neurological symptoms became dead, suggesting that neurological involvement may be one cause of death.
2019 年冠状病毒病（COVID-19）的爆发是由严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2）引起的，已成为对全球健康的重大和紧迫威胁。本综述为 SARS-CoV-2 感染中枢神经系统（CNS）提供了有力支持，并揭示了 SARS-CoV-2 感染致死的神经机制。在已发表的数据中，仅 1.28%接受过脑脊液（CSF）检测的 COVID-19 患者的 CSF 中 SARS-CoV-2 检测呈阳性。然而，这并不意味着大多数 COVID-19 患者不存在 CNS 感染，因为尸检研究表明，一些中枢神经系统感染的患者 CSF 检测 SARS-CoV-2 结果呈阴性。在迄今为止报告的 20 项神经病理学研究中，有 9 项研究的 58 例病例中检测到 SARS-CoV-2，其中 3 项研究提供了 COVID-19 患者中枢神经系统感染的详细信息。几乎所有的体外和体内实验都支持 SARS-CoV-2 的神经侵袭潜力。在感染动物中，SARS-CoV-2 存在于不同脑区的神经元内，伴有广泛的神经病理学改变，与 COVID-19 患者的临床症状一致。有几条证据表明 SARS-CoV-2 利用造血途径进入 CNS。但更多的证据支持跨神经元假说。已经发现 SARS-CoV-2 通过嗅觉、味觉和三叉神经途径侵入大脑，特别是在感染的早期阶段。有神经功能缺损的严重 COVID-19 患者死亡率更高，只有出现神经症状的感染动物死亡，这表明神经受累可能是死亡的一个原因。
