目的:严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染可引起广泛的神经系统并发症,但其在疾病急性期的神经渗透性尚不清楚。
方法:使用超速离心从接受癫痫手术的患者的脑活检组织中分离细胞外囊泡,并通过蛋白质印迹和qPCR分析病毒蛋白和RNA的存在,分别。通过免疫组织化学评估活检组织是否存在微血管损伤,并与其他三种非COVID外科癫痫脑组织进行比较。
结果:我们证明了在SARS-CoV-2感染后不久接受癫痫手术的患者的细胞外囊泡和大脑中的微血管疾病中存在病毒核衣壳蛋白。内皮细胞活化表现为PECAM-1水平升高,与对照非COVID外科癫痫脑组织相比,活检组织中与纤维蛋白原渗漏和免疫细胞浸润有关。
结论:尽管缺乏病毒在脑内复制的证据,核衣壳蛋白的存在与疾病特异性内皮细胞活化有关,纤维蛋白原渗漏,和免疫细胞浸润。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause a wide range of neurologic complications; however, its neuropenetrance during the acute phase of the illness is unknown.
Extracellular vesicles were isolated from brain biopsy tissue from a patient undergoing epilepsy surgery using ultracentrifugation and analyzed by Western blot and qPCR for the presence of virus protein and RNA, respectively. Biopsy tissue was assessed by immunohistochemistry for the presence of microvascular damage and compared with 3 other non-COVID surgical epilepsy brain tissues.
We demonstrate the presence of viral nucleocapsid protein in extracellular vesicles and microvascular disease in the brain of a patient undergoing epilepsy surgery shortly after SARS-CoV-2 infection. Endothelial cell activation was indicated by increased levels of platelet endothelial cell adhesion molecule-1 and was associated with fibrinogen leakage and immune cell infiltration in the biopsy tissue as compared with control non-COVID surgical epilepsy brain tissues.
Despite the lack of evidence of viral replication within the brain, the presence of the nucleocapsid protein was associated with disease-specific endothelial cell activation, fibrinogen leakage, and immune cell infiltration.