Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19
Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19
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DOI：
10.1212/wnl.0000000000010111
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发表时间：
2020-09-22
期刊：
影响因子：
9.9
通讯作者：
Gisslen, Magnus
中科院分区：
文献类型：
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作者：
Kanberg, Nelly;Ashton, Nicholas J.;Gisslen, Magnus
目的通过测定CNS损伤的血浆生物标志物，验证2019冠状病毒病（COVID-19）对CNS有影响的假设。方法我们招募了47例轻度（n = 20）、中度（n = 9）和重度（n = 18）COVID-19患者，并通过单分子阵列检测了2种CNS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）和胶质细胞酸性蛋白（GFAP;星形胶质细胞活化/损伤的标志物），在就诊时收集的样品中，并在平均11.4天后再次在一个亚组中。横断面结果与来自一个独立队列的33名年龄匹配的对照组的结果进行了比较。结果重度COVID-19患者的血浆GFAP（p= 0.001）和NfL（p< 0.001）浓度高于对照组，而中度疾病患者的GFAP也升高（p= 0.03）。在严重疾病患者中，血浆GFAP的早期峰值在随访时降低（p< 0.01），而NfL从第一次到最后一次随访显示持续增加（p< 0.01），这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。结论我们显示了中重度COVID-19患者神经元损伤和胶质细胞活化的神经化学证据。需要进一步研究来阐明COVID-19相关CNS损伤的频率和性质及其与临床定义的CNS事件（如缺氧和缺血事件）的关系，以及与全身性严重急性呼吸综合征冠状病毒2型感染和随后的免疫激活更密切相关的机制，并评估监测血浆NfL和GFAP在这组患者管理中的临床效用。
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 (p= 0.001) and NfL (p< 0.001) than controls, while GFAp was also increased in patients with moderate disease (p= 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p< 0.01), while NfL showed a sustained increase from first to last follow-up (p< 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.