Seven coronavirus (CoV) species are known human pathogens: the epidemic viruses SARS-CoV, SARS-CoV-2, and MERS-CoV and those continuously circulating in human populations since initial isolation: HCoV-OC43, HCoV-229E, HCoV-HKU1, and HCoV-NL63. All have associations with human central nervous system (CNS) dysfunction. In infants and young children, the most common CNS phenomena are febrile seizures; in adults, non-focal abnormalities that may be either neurologic or constitutional. Neurotropism and neurovirulence are dependent in part on CNS expression of cell surface receptors mediating viral entry, and host immune response. In adults, CNS receptors for epidemic viruses are largely expressed on brain vasculature, whereas receptors for less pathogenic viruses are present in vasculature, brain parenchyma, and olfactory neuroepithelium, dependent upon viral species. Human coronaviruses can infect circulating mononuclear cells, but meningoencephalitis is rare. Well-documented human neuropathologies are infrequent and, for SARS, MERS, and COVID-19, can entail cerebrovascular accidents originating extrinsically to brain. There is evidence of neuronal infection in the absence of inflammatory infiltrates with SARS-CoV, and CSF studies of rare patients with seizures have demonstrated virus but no pleocytosis. In contrast to human disease, animal models of neuropathogenesis are well developed, and pathologies including demyelination, neuronal necrosis, and meningoencephalitis are seen with both native CoVs as well as human CoVs inoculated into nasal cavities or brain. This review covers basic CoV biology pertinent to CNS disease; the spectrum of clinical abnormalities encountered in infants, children, and adults; and the evidence for CoV infection of human brain, with reference to pertinent animal models of neuropathogenesis.

七种冠状病毒 (CoV) 是已知的人类病原体：流行病毒 SARS-CoV、SARS-CoV-2 和 MERS-CoV 以及自最初隔离以来在人群中持续传播的病毒：HCoV-OC43、HCoV-229E、HCoV-HKU1和 HCoV-NL63。所有这些都与人类中枢神经系统 (CNS) 功能障碍有关。在婴幼儿中，最常见的中枢神经系统现象是热性惊厥；在成人中，可能是神经系统或体质的非局灶性异常。神经嗜性和神经毒力部分依赖于介导病毒进入和宿主免疫反应的细胞表面受体的 CNS 表达。在成人中，流行病毒的 CNS 受体主要在脑血管系统中表达，而致病性较低的病毒受体则存在于血管系统、脑实质和嗅觉神经上皮中。取决于病毒种类。人类冠状病毒可以感染循环单核细胞，但脑膜脑炎很少见。有据可查的人类神经病理学并不常见，对于 SARS、MERS 和 COVID-19，可能会导致脑外源性脑血管意外。有证据表明在没有 SARS-CoV 炎症浸润的情况下存在神经元感染，对罕见癫痫发作患者的脑脊液研究显示病毒但没有细胞增多。与人类疾病相比，神经发病机制的动物模型得到了很好的发展，在天然 CoV 以及接种到鼻腔或大脑中的人类 CoV 中都可以看到包括脱髓鞘、神经元坏死和脑膜脑炎在内的病理。这篇综述涵盖了与 CNS 疾病相关的基本 CoV 生物学；婴儿、儿童和成人的临床异常谱；以及人脑感染冠状病毒的证据，参考相关的神经发病动物模型。