Domingues K Z A, Cobre A F, Lazo R E L, Amaral L S, Ferreira L M, Tonin F S, Pontarolo R
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Paraná, Curitiba, PR, 80210-170, Brazil.
H&TRC- Health & Technology Research Center, ESTeSL, Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, 1990-096, Lisbon, Portugal.
J Neurol. 2024 Jan;271(1):1-23. doi: 10.1007/s00415-023-12090-6. Epub 2023 Nov 28.
This study aimed to synthesize the existing evidence on biomarkers related to coronavirus disease 2019 (COVID-19) patients who presented neurological events.
A systematic review of observational studies (any design) following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Collaboration recommendations was performed (PROSPERO: CRD42021266995). Searches were conducted in PubMed and Scopus (updated April 2023). The methodological quality of nonrandomized studies was assessed using the Newcastle‒Ottawa Scale (NOS). An evidence gap map was built considering the reported biomarkers and NOS results.
Nine specific markers of glial activation and neuronal injury were mapped from 35 studies published between 2020 and 2023. A total of 2,237 adult patients were evaluated in the included studies, especially during the acute phase of COVID-19. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) biomarkers were the most frequently assessed (n = 27 studies, 77%, and n = 14 studies, 40%, respectively). Although these biomarkers were found to be correlated with disease severity and worse outcomes in the acute phase in several studies (p < 0.05), they were not necessarily associated with neurological events. Overall, 12 studies (34%) were judged as having low methodological quality, 9 (26%) had moderate quality, and 9 (26%) had high quality.
Different neurological biomarkers in neurosymptomatic COVID-19 patients were identified in observational studies. Although the evidence is still scarce and conflicting for some biomarkers, well-designed longitudinal studies should further explore the pathophysiological role of NfL, GFAP, and tau protein and their potential use for COVID-19 diagnosis and management.
本研究旨在综合现有的关于2019冠状病毒病（COVID-19）出现神经事件患者的生物标志物的证据。
按照系统评价和Meta分析的首选报告项目（PRISMA）指南以及Cochrane协作网的建议，对观察性研究（任何设计）进行了系统评价（国际前瞻性系统评价注册库：CRD42021266995）。在PubMed和Scopus（2023年4月更新）中进行了检索。使用纽卡斯尔-渥太华量表（NOS）评估非随机研究的方法学质量。根据报告的生物标志物和NOS结果构建了证据缺口图。
从2020年至2023年发表的35项研究中梳理出9种神经胶质激活和神经元损伤的特定标志物。纳入研究共评估了2237例成年患者，尤其是在COVID-19急性期。神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）生物标志物是评估最频繁的（分别为n = 27项研究，77%；n = 14项研究，40%）。尽管在多项研究中发现这些生物标志物在急性期与疾病严重程度和较差预后相关（p < 0.05），但它们不一定与神经事件相关。总体而言，12项研究（34%）被判定方法学质量低，9项（26%）质量中等，9项（26%）质量高。
在观察性研究中确定了有神经症状的COVID-19患者的不同神经生物标志物。尽管对于某些生物标志物的证据仍然稀少且相互矛盾，但精心设计的纵向研究应进一步探索NfL、GFAP和tau蛋白的病理生理作用及其在COVID-19诊断和管理中的潜在用途。
