Anti-SARS-CoV-2 antibodies in the CSF, blood-brain barrier dysfunction, and neurological outcome: Studies in 8 stuporous and comatose patients.
Anti-SARS-CoV-2 antibodies in the CSF, blood-brain barrier dysfunction, and neurological outcome: Studies in 8 stuporous and comatose patients.
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DOI：
10.1212/nxi.0000000000000893
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
Dalakas MC
中科院分区：
文献类型：
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作者：
Alexopoulos H;Magira E;Bitzogli K;Kafasi N;Vlachoyiannopoulos P;Tzioufas A;Kotanidou A;Dalakas MC
[目的]探讨冠状病毒病2019患者脑病及长期昏迷或昏迷状态的病理生理机制(新冠肺炎)。采用美国食品和药物管理局(FDA)批准并独立验证的ELISA法，对8名有脑病症状的新冠肺炎患者进行了血清和脑脊液中SARS-CoV-2抗体的检测。用白蛋白和免疫球蛋白G(Ig G)指数进一步检测血脑屏障(BBB)完整性和免疫球蛋白G(Ig G)鞘内合成。还对脑脊液进行了自身免疫性脑炎抗体和14-3-3检测，14-3-3是正在进行的神经变性的标志。所有患者的脑脊液中均有抗SARS-CoV-2抗体，8例患者中有4例有高滴度，与高血清值相当。1例鞘内合成抗SARS-CoV-2抗体，3例血脑屏障破坏。4例患者脑脊液14-3-3-蛋白呈阳性，提示正在发生神经变性。所有患者脑脊液中自身免疫性脑炎抗体和SARS-CoV-2聚合酶链式反应均为阴性。除持续性脑病体征外，所有患者均无任何局灶性神经体征、病史或特定神经系统疾病。在昏迷或脑病患者的脑脊液中检测到高效价的抗SARS-CoV-2抗体，提示鞘内免疫球蛋白合成或血脑屏障破坏。血脑屏障受损可能促进细胞因子和炎症介质进入中枢神经系统，促进神经炎症和神经变性。这些观察结果突显了前瞻性脑脊液研究的必要性，以确定抗SARS-CoV-2抗体的致病作用，并确定早期治疗干预措施。
To investigate the pathophysiologic mechanism of encephalopathy and prolonged comatose or stuporous state in severally ill patients with coronavirus disease 2019 (COVID-19). Eight COVID-19 patients with signs of encephalopathy were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the serum and CSF using a Food and Drug Administration-approved and independently validated ELISA. Blood-brain barrier (BBB) integrity and immunoglobulin G (IgG) intrathecal synthesis were further tested using albumin and IgG indices. The CSF was also tested for autoimmune encephalitis antibodies and 14-3-3, a marker of ongoing neurodegeneration. All patients had anti–SARS-CoV-2 antibodies in their CSF, and 4 of 8 patients had high titers, comparable to high serum values. One patient had anti–SARS-CoV-2 IgG intrathecal synthesis, and 3 others had disruption of the blood-brain barrier. The CSF in 4 patients was positive for 14-3-3-protein suggesting ongoing neurodegeneration. In all patients, the CSF was negative for autoimmune encephalitis antibodies and SARS-CoV-2 by PCR. None of the patients, apart from persistent encephalopathic signs, had any focal neurologic signs or history or specific neurologic disease. High-titer anti-SARS-CoV-2 antibodies were detected in the CSF of comatose or encephalopathic patients demonstrating intrathecal IgG synthesis or BBB disruption. A disrupted BBB may facilitate the entry of cytokines and inflammatory mediators into the CNS enhancing neuroinflammation and neurodegeneration. The observations highlight the need for prospective CSF studies to determine the pathogenic role of anti–SARS-CoV-2 antibodies and identify early therapeutic interventions.