COVID-19 intensive care patients occasionally develop neurological symptoms. The absence of SARS-CoV-2 in most cerebrospinal fluid (CSF) samples suggests the involvement of further mechanisms including autoimmunity. We therefore determined whether anti-neuronal or anti-glial autoantibodies are present in eleven consecutive severely ill COVID-19 patients presenting with unexplained neurological symptoms. These included myoclonus, cranial nerve involvement, oculomotor disturbance, delirium, dystonia and epileptic seizures. Most patients showed signs of CSF inflammation and increased levels of neurofilament light chain. All patients had anti-neuronal autoantibodies in serum or CSF when assessing a large panel of autoantibodies against intracellular and surface antigens relevant for central nervous system diseases using cell-based assays and indirect immunofluorescence on murine brain sections. Antigens included proteins well-established in clinical routine, such as Yo or NMDA receptor, but also a variety of specific undetermined epitopes on brain sections. These included vessel endothelium, astrocytic proteins and neuropil of basal ganglia, hippocampus or olfactory bulb. The high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a causal relationship to clinical symptoms, in particular to hyperexcitability (myoclonus, seizures). While several underlying autoantigens still await identification in future studies, presence of autoantibodies may explain some aspects of multi-organ disease in COVID-19 and can guide immunotherapy in selected cases.

中文翻译：

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具有神经系统症状的COVID-19患者中高频率的脑脊液自身抗体

COVID-19重症监护患者偶尔会出现神经系统症状。大多数脑脊液（CSF）样品中均未出现SARS-CoV-2，这提示了包括自身免疫在内的其他机制的参与。因此，我们确定了十一名出现无法解释的神经系统症状的重症COVID-19连续患者中是否存在抗神经胶质或抗神经胶质自身抗体。这些包括肌阵挛，颅神经受累，动眼障碍，del妄，肌张力障碍和癫痫发作。大多数患者显示出CSF炎症迹象和神经丝轻链水平升高。当使用基于细胞的测定法和鼠脑切片的间接免疫荧光法评估一大批针对与中枢神经系统疾病相关的细胞内和表面抗原的自身抗体时，所有患者的血清或CSF中均具有抗神经元自身抗体。抗原包括临床常规中公认的蛋白质，例如Yo或NMDA受体，还包括大脑切片上的各种特定的不确定表位。这些包括血管内皮，星形细胞蛋白和基底神经节，海马或嗅球的神经纤维。在没有其他解释的情况下，针对大脑的自身抗体的高频率提示与临床症状，尤其是与过度兴奋性（肌阵挛，癫痫发作）有因果关系。虽然一些潜在的自身抗原仍在等待将来的研究鉴定，