Department of Clinical Science and Translational Medicine, University of Rome Tor Vergata, Rome, Italy.
Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal.
Eur J Neurol. 2020 Sep;27(9):1764-1773. doi: 10.1111/ene.14277. Epub 2020 May 22.
The current coronavirus disease (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS-CoV-2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS-CoV-2. One key finding that may unify these pathogens is that all require angiotensin-converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS-CoV-2 binds to cell membranes, binds angiotensin-converting enzyme 2 with a higher affinity compared with SARS-CoV. The expression of this receptor in neurons and endothelial cells hints that SARS-CoV-2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune-mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune-mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID-19.
当前由新型严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的冠状病毒病（COVID-19）疫情，提出了这种病毒可能具有潜在神经毒性的可能性。实际上，已经有报道称 SARS-CoV-2 感染后的神经后遗症，并强调了从转化的角度考虑冠状病毒（CoV）对神经系统影响的相关性。在 2002 年和 2012 年流行期间，由结构上相似的 CoV 引起的 SARS 和中东呼吸综合征的动物模型为 CoV 对神经系统的影响以及 SARS-CoV-2 向中枢神经系统传播的可能性提供了宝贵的数据。可能统一这些病原体的一个关键发现是，所有这些病原体都需要血管紧张素转换酶 2 作为细胞进入受体。CoV 刺突糖蛋白是 SARS-CoV-2 与细胞膜结合的部位，与 SARS-CoV 相比，它与血管紧张素转换酶 2 的结合亲和力更高。这种受体在神经元和内皮细胞中的表达表明，与以前的 CoV 相比，SARS-CoV-2 可能具有更高的神经侵袭潜力。然而，仍需要确定这种侵袭性如何导致呼吸衰竭或直接造成神经损伤。直接和间接机制都可能相关。由宿主免疫介导的反应差异引起的临床异质性将需要广泛的研究。因此，开发疾病模型以预测新出现的神经并发症，并在短期内探索直接或免疫介导的致病性机制，从中期来看，具有重要意义。在这篇简短的综述中，我们描述了以前 CoV 感染模型的现有知识，并讨论了它们对 COVID-19 的潜在相关性。
