Anand Harnadar, Ende Victoria, Singh Gurinder, Qureshi Irfan, Duong Tim Q, Mehler Mark F
The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, United States.
Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States.
Front Neurosci. 2021 Aug 27;15:727060. doi: 10.3389/fnins.2021.727060. eCollection 2021.
SARS-CoV-2 infection is associated with a spectrum of acute neurological syndromes. A subset of these syndromes promotes higher in-hospital mortality than is predicted by traditional parameters defining critical care illness. This suggests that deregulation of components of the central and peripheral nervous systems compromises the interplay with systemic cellular, tissue and organ interfaces to mediate numerous atypical manifestations of COVID-19 through impairments in organismal homeostasis. This unique dyshomeostasis syndrome involves components of the ACE-2/1 lifecycles, renin-angiotensin system regulatory axes, integrated nervous system functional interactions and brain regions differentially sculpted by accelerated evolutionary processes and more primordial homeostatic functions. These biological contingencies suggest a mechanistic blueprint to define long-term neurological sequelae and systemic manifestations such as premature aging phenotypes, including organ fibrosis, tissue degeneration and cancer. Therapeutic initiatives must therefore encompass innovative combinatorial agents, including repurposing FDA-approved drugs targeting components of the autonomic nervous system and recently identified products of SARS-CoV-2-host interactions.
新型冠状病毒2型（SARS-CoV-2）感染与一系列急性神经综合征相关。其中一部分综合征导致的院内死亡率高于传统重症监护疾病参数所预测的死亡率。这表明中枢和外周神经系统成分的失调会损害与全身细胞、组织和器官界面的相互作用，通过破坏机体稳态来介导新冠肺炎的众多非典型表现。这种独特的稳态失调综合征涉及血管紧张素转换酶2/1（ACE-2/1）生命周期、肾素-血管紧张素系统调节轴、整合神经系统功能相互作用以及由加速进化过程和更原始的稳态功能塑造的不同脑区的成分。这些生物学意外情况提示了一个机制蓝图，以定义长期神经后遗症和全身表现，如过早衰老表型，包括器官纤维化、组织退化和癌症。因此，治疗方案必须包括创新的联合药物，包括重新利用美国食品药品监督管理局（FDA）批准的针对自主神经系统成分的药物以及最近发现的SARS-CoV-2与宿主相互作用的产物。
