在 COVID-19 中常见的神经胶质细胞和神经元损伤的神经化学证据。
Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19.
机构信息
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
出版信息
Neurology. 2020 Sep 22;95(12):e1754-e1759. doi: 10.1212/WNL.0000000000010111. Epub 2020 Jun 16.
OBJECTIVE
To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.
METHODS
We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.
RESULTS
The patients with severe COVID-19 had higher plasma concentrations of GFAp ( = 0.001) and NfL ( < 0.001) than controls, while GFAp was also increased in patients with moderate disease ( = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up ( < 0.01), while NfL showed a sustained increase from first to last follow-up ( < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.
CONCLUSION
We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
目的
通过测量中枢神经系统损伤的血浆生物标志物，检验 2019 年冠状病毒病（COVID-19）对中枢神经系统有影响的假说。
方法
我们招募了 47 名轻症（n=20）、中度（n=9）或重症（n=18）COVID-19 患者，在入院时和平均 11.4 天后再次采集样本，使用单分子阵列测量了 2 种中枢神经系统损伤的血浆生物标志物，神经丝轻链蛋白（NfL；轴突内神经元损伤的标志物）和胶质纤维酸性蛋白（GFAp；星形胶质细胞激活/损伤的标志物）。横断面结果与来自独立队列的 33 名年龄匹配对照者的结果进行了比较。
结果
重症 COVID-19 患者的血浆 GFAp（=0.001）和 NfL（<0.001）浓度高于对照组，而中度疾病患者的 GFAp 也升高（=0.03）。在重症患者中，血浆 GFAp 的早期峰值在随访时降低（<0.01），而 NfL 从首次到最后一次随访均持续升高（<0.01），可能反映了早期星形胶质细胞反应和更延迟的轴突损伤的顺序。
结论
我们在中度和重度 COVID-19 患者中发现了神经元损伤和神经胶质激活的神经化学证据。需要进一步研究来阐明 COVID-19 相关中枢神经系统损伤的频率和性质，以及其与临床定义的中枢神经系统事件（如缺氧和缺血事件）的关系，以及与更密切相关的全身严重急性呼吸系统综合征冠状病毒 2 感染和随之而来的免疫激活的关系，并评估监测血浆 NfL 和 GFAp 在管理这群患者中的临床应用。
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