Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes a highly contagious respiratory disease referred to as COVID‐19. However, emerging evidence indicates that a small but growing number of COVID‐19 patients also manifest neurological symptoms, suggesting that SARS‐CoV‐2 may infect the nervous system under some circumstances. SARS‐CoV‐2 primarily enters the body through the epithelial lining of the respiratory and gastrointestinal tracts, but under certain conditions this pleiotropic virus may also infect peripheral nerves and gain entry into the central nervous system (CNS). The brain is shielded by various anatomical and physiological barriers, most notably the blood–brain barrier (BBB) which functions to prevent harmful substances, including pathogens and pro‐inflammatory mediators, from entering the brain. The BBB is composed of highly specialized endothelial cells, pericytes, mast cells and astrocytes that form the neurovascular unit, which regulates BBB permeability and maintains the integrity of the CNS. In this review, potential routes of viral entry and the possible mechanisms utilized by SARS‐CoV‐2 to penetrate the CNS, either by disrupting the BBB or infecting the peripheral nerves and using the neuronal network to initiate neuroinflammation, are briefly discussed. Furthermore, the long‐term effects of SARS‐CoV‐2 infection on the brain and in the progression of neurodegenerative diseases known to be associated with other human coronaviruses are considered. Although the mechanisms of SARS‐CoV‐2 entry into the CNS and neurovirulence are currently unknown, the potential pathways described here might pave the way for future research in this area and enable the development of better therapeutic strategies.

中文翻译：

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严重急性呼吸综合征冠状病毒2可能是一种未被充分认识的中枢神经系统病原体。


严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 会引起一种高度传染性呼吸道疾病，称为 COVID-19。然而，新出现的证据表明，少数但数量不断增加的 COVID-19 患者也出现神经系统症状，这表明 SARS-CoV-2 在某些情况下可能会感染神经系统。 SARS-CoV-2 主要通过呼吸道和胃肠道的上皮层进入人体，但在某些条件下，这种多效性病毒也可能感染周围神经并进入中枢神经系统 (CNS)。大脑受到各种解剖学和生理学屏障的保护，尤其是血脑屏障（BBB），其功能是防止有害物质（包括病原体和促炎介质）进入大脑。 BBB 由高度特化的内皮细胞、周细胞、肥大细胞和星形胶质细胞组成，形成神经血管单元，调节 BBB 通透性并维持 CNS 的完整性。在这篇综述中，简要讨论了病毒进入的潜在途径以及 SARS-CoV-2 通过破坏血脑屏障或感染周围神经并利用神经元网络引发神经炎症来渗透中枢神经系统的可能机制。此外，还考虑了 SARS-CoV-2 感染对大脑以及已知与其他人类冠状病毒相关的神经退行性疾病进展的长期影响。尽管 SARS-CoV-2 进入中枢神经系统和神经毒力的机制目前尚不清楚，但本文描述的潜在途径可能为该领域的未来研究铺平道路，并能够开发更好的治疗策略。