COVID-19 伴有神经系统症状患者的脑脊液生物标志物：病例系列研究。
CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series.
机构信息
From the Department of Infectious Diseases (A.E., N.K., L.H., L.-M.A., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg; Region Västra Götaland (A.E., N.K., L.H., L.-M.A., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden; Institutes of Medical Biochemistry (J.G.) and Biological Chemistry (D.F.), Medical University of Innsbruck, Biocenter, Austria; Department of Neurology (R.W.P.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London.
出版信息
Neurology. 2021 Jan 12;96(2):e294-e300. doi: 10.1212/WNL.0000000000010977. Epub 2020 Oct 1.
OBJECTIVE
To explore whether hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neurologic symptoms have evidence of CNS infection, inflammation, and injury using CSF biomarker measurements.
METHODS
We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β-microglobulin, and immunoglobulin G index), blood-brain barrier integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe coronavirus disease 2019 (COVID-19) and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4 of 6), suspected meningitis (1 of 6), and dysgeusia (1 of 6). SARS-CoV-2 infection was confirmed by real-time PCR analysis of nasopharyngeal swabs.
RESULTS
SARS-CoV-2 RNA was detected in the plasma of 2 patients (cycle threshold [Ct] value 35.0-37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in 1 but not in a second real-time PCR assay. CSF neopterin (median 43.0 nmol/L) and β-microglobulin (median 3.1 mg/L) were increased in all. Median immunoglobulin G index (0.39), albumin ratio (5.35), and CSF white blood cell count (<3 cells/µL) were normal in all, while CSF NfL was elevated in 2 patients.
CONCLUSION
Our results in patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.
目的
通过检测脑脊液（CSF）生物标志物来探讨伴有神经系统症状的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染住院患者是否存在中枢神经系统（CNS）感染、炎症和损伤的证据。
方法
我们评估了 6 例伴有中度至重度 2019 冠状病毒病（COVID-19）和神经系统症状且已行诊断性腰椎穿刺的患者的 CSF 中 SARS-CoV-2 RNA 以及鞘内炎症的 CSF 生物标志物（CSF 白细胞计数、新蝶呤、β-微球蛋白和免疫球蛋白 G 指数）、血脑屏障完整性（白蛋白比值）和轴索损伤（CSF 神经丝轻链蛋白[NfL]）。神经系统症状和体征包括脑病表现（6 例中的 4 例）、疑似脑膜炎（6 例中的 1 例）和味觉障碍（6 例中的 1 例）。通过实时 PCR 分析鼻咽拭子来确认 SARS-CoV-2 感染。
结果
2 例患者的血浆中检测到 SARS-CoV-2 RNA（Ct 值 35.0-37.0），3 例患者的 CSF 中低水平检测到 SARS-CoV-2 RNA（Ct 值 37.2、38.0、39.0），但在第 2 次实时 PCR 检测中均未检测到。所有患者的 CSF 新蝶呤（中位数 43.0 nmol/L）和β-微球蛋白（中位数 3.1 mg/L）均升高。所有患者的免疫球蛋白 G 指数（0.39）、白蛋白比值（5.35）和 CSF 白细胞计数（<3 个/µL）均正常，而 2 例患者的 CSF NfL 升高。
结论
我们对伴有神经系统症状的 COVID-19 患者的研究结果提示一种不常见的 CSF 炎症模式，即可溶性标志物升高，但白细胞反应和其他免疫特征不典型的 CNS 病毒感染不存在。虽然我们最初的假设集中在 SARS-CoV-2 对 CNS 的入侵，但我们无法令人信服地检测到 SARS-CoV-2 是 CNS 炎症的潜在驱动因素。这些特征将 COVID-19 的 CSF 与其他病毒性 CNS 感染区分开来，并提出了关于 SARS-CoV-2 感染 CNS 发病机制的基本问题。
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