To the Editor, The current pandemic that has paralyzed the world economy is caused by a new coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)]. Although the lung is a major target organ of the virus, it can also strike other parts of the body including the nervous system. Neurologic presentations of COVID-19 are ranging from nonspecific and moderate to severe. Most patients have mild symptoms like headache and make a good recovery. However, a minority of patients develop severe complications with unfavorable outcomes including cerebrovascular diseases [1]. SARS-CoV-2 is considered novel because of its special features. But simultaneously, there are similarities between this and other betacoronaviruses. For instance, genomic analysis indicated that Middle East respiratory syndrome coronavirus and SARS-CoV share high degrees of sequence homology with SARS-CoV-2. Moreover, SARS-CoV and SARS-CoV-2 use the same host receptor for cell entry [2]. Like other coronaviruses, SARS-CoV-2 is neurotropic and may spread to the nervous system via similar mechanisms. Neurotropic and neuroinvasive properties of SARSCoV-2 are supported by several observations including the presence of virus particles in the cerebrospinal fluid of patients with significant nervous system symptoms [3]. Currently, it is difficult to distinguish whether neurological complications of COVID-19 are a consequence of direct or indirect effects of viral infection. However, existing data highlight the importance of considering both effects. Direct effects may occur by multiple mechanisms including viral transit across the cribriform plate or olfactory bulb to brain. Another mechanism relies on blood circulation and angiotensin-converting enzyme 2 (ACE2) receptors that are expressed on glial cells, neurons, and capillary endothelium and are involved in virus entry [4]. In addition to direct adverse consequences, several indirect mechanisms have been proposed to account for neuropathologic properties of SARS-CoV-2. For instance, viral replication within the lung pneumocytes may lead to hypoxic conditions and gas exchange disorders in the nervous system. Another mechanism appears to be related to ACE2 which acts as a cardiocerebral vascular protection factor and plays an important role in blood pressure regulation and antiatherosclerosis mechanisms. Virus binding to ACE2 receptors can lead to hypertension and increase the risk of ischemic stroke and cerebral hemorrhage [1, 4]. The third indirect mechanism is linked to the host immune response against virus. Some evidence indicates that neurological symptoms of COVID-19 could be induced by uncontrolled production of cytokines. These mediators are produced by different cells including glial cells. The ability of these cells to produce proinflammatory cytokines has also been demonstrated in experimental models, after corona virus infection [4]. Molecular mimicry that could be associated with the development of autoimmunity is another mechanism by which SARS-

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COVID-19 的神经系统表现：我们可以从其他冠状病毒中学到什么

致编辑，当前使世界经济瘫痪的大流行病是由一种新型冠状病毒[严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）]引起的。虽然肺是病毒的主要靶器官，但它也可以攻击身体的其他部位，包括神经系统。COVID-19 的神经系统表现从非特异性和中度到重度不等。大多数患者有轻微的头痛等症状，恢复良好。然而，少数患者会出现严重的并发症，包括脑血管疾病[1]。SARS-CoV-2 因其特殊性而被认为是新颖的。但同时，这种病毒与其他β冠状病毒也有相似之处。例如，基因组分析表明，中东呼吸综合征冠状病毒和 SARS-CoV 与 SARS-CoV-2 具有高度的序列同源性。此外，SARS-CoV 和 SARS-CoV-2 使用相同的宿主受体进入细胞 [2]。与其他冠状病毒一样，SARS-CoV-2 是嗜神经的，可能通过类似的机制传播到神经系统。一些观察结果支持了 SARSCoV-2 的嗜神经和神经侵袭特性，包括在具有显着神经系统症状的患者的脑脊液中存在病毒颗粒 [3]。目前，很难区分 COVID-19 的神经系统并发症是否是病毒感染的直接或间接影响的结果。然而，现有数据强调了考虑这两种影响的重要性。直接影响可能通过多种机制发生，包括病毒穿过筛板或嗅球到达大脑。另一种机制依赖于血液循环和血管紧张素转换酶 2 (ACE2) 受体，这些受体在神经胶质细胞、神经元和毛细血管内皮上表达并参与病毒进入 [4]。除了直接的不良后果外，还提出了几种间接机制来解释 SARS-CoV-2 的神经病理学特性。例如，肺肺细胞内的病毒复制可能导致神经系统缺氧和气体交换障碍。另一种机制似乎与 ACE2 相关，ACE2 作为一种心脑血管保护因子，在血压调节和抗动脉粥样硬化机制中发挥重要作用。病毒与 ACE2 受体结合可导致高血压并增加缺血性中风和脑出血的风险 [1, 4]。第三种间接机制与宿主对病毒的免疫反应有关。一些证据表明，COVID-19 的神经系统症状可能是由不受控制的细胞因子产生引起的。这些介质由不同的细胞产生，包括神经胶质细胞。在冠状病毒感染后的实验模型中，这些细胞产生促炎细胞因子的能力也得到了证明 [4]。可能与自身免疫发展相关的分子模拟是 SARS- 一些证据表明，COVID-19 的神经系统症状可能是由不受控制的细胞因子产生引起的。这些介质由不同的细胞产生，包括神经胶质细胞。在冠状病毒感染后的实验模型中，这些细胞产生促炎细胞因子的能力也得到了证明 [4]。可能与自身免疫发展相关的分子模拟是 SARS- 一些证据表明，COVID-19 的神经系统症状可能是由不受控制的细胞因子产生引起的。这些介质由不同的细胞产生，包括神经胶质细胞。在冠状病毒感染后的实验模型中，这些细胞产生促炎细胞因子的能力也得到了证明 [4]。可能与自身免疫发展相关的分子模拟是 SARS-