Elevation of Neural injury markers in Patients with Neurologic Sequelae after Hospitalization for SARS-CoV-2 Infection. Spanos et al.

Background: Patients with SARS-CoV-2 infection (COVID-19) risk developing long-term neurologic symptoms after infection, though risk factors and mechanisms for this phenomenon remain largely unknown. This study seeks to identify biomarkers associated with neurologic sequelae in patients after hospitalization for SARS-CoV-2 infection.
Methods: Plasma samples and clinical outcome data were retrospectively analyzed from an observational cohort study conducted from 3/19/20 to 3/20/2021. Three neuronal injury markers; Glial fibrillary astrocytic protein (GFAP), Neurofilament light chain (NF-L), and Tau, and two inflammatory plasma protein markers; Monocyte Chemoattractant Protein-4 (MCP-4) and T-cell Immunoglobulin and Mucin domain protein-3 (TIM-3), were measured. SARS-CoV-2 positive patients were followed for one year after hospitalization using post-SARS-CoV-2 online questionnaires and virtual visits. Sixty-one adults with SARS-CoV-2 infection were included. Sixty hospitalized adults from the pre-SARS-CoV-2 era were matched according to age, sex, ICU duration, and qSOFA scores and served as historical controls.
Findings: Sixty-one patients with confirmed SARS-CoV-2 infection were included (53 for outcomes) of which 21 (40%) developed neurologic symptoms during one year of recovery. In the historical control cohort, from forty-seven patients that were followed, 7 (14%) developed persisting neurological symptoms. COVID-19 Patients with neurologic sequelae were older and had more severe disease, including signs of hepatic injury, decreased renal function, leukocytosis, and higher levels of inflammatory markers. COVID-19 was associated with an additional risk for neurological sequelae compared to controls. Glial fibrillary astrocytic protein (GFAP) and Neurofilament light chain (NF-L) were significantly elevated in SARS-CoV-2 infection compared to control patients. After adjusting for age, sex, and disease severity, GFAP and NF-L remained significantly associated with longer-term neurological symptoms in patients with SARS-CoV-2 infection.
Interpretation:
A significant proportion of patients who recovered from acute COVID-19 infection develop neurological sequelae in the year after hospitalization. Compared to historical controls, patients with SARS-CoV-2 infection were more likely to have neurological symptoms during one year of follow-up after hospitalization. Plasma GFAP and NF-L levels are higher in patients hospitalized for SARS-CoV-2 infection relative to control patients and are associated with neurological symptoms.

背景：SARS-CoV-2感染（COVID-19）患者感染后存在发展长期神经学症状的风险，尽管此现象的风险因素和机制尚大多未明。本研究旨在识别与SARS-CoV-2感染后住院患者神经学后遗症相关的生物标志物。方法：对从2020年3月19日至2021年3月20日进行的观察性队列研究中的血浆样本和临床结局数据进行回顾性分析。测量了三种神经元损伤标志物：星形胶质纤维蛋白（GFAP）、神经丝轻链（NF-L）和Tau，以及两种炎症血浆蛋白标志物：单核细胞趋化蛋白-4（MCP-4）和T细胞免疫球蛋白和粘蛋白结构域蛋白-3（TIM-3）。对SARS-CoV-2阳性患者进行住院后一年内的随访，使用SARS-CoV-2在线问卷和虚拟访问。纳入61名SARS-CoV-2感染成人。根据年龄、性别、ICU住院时间和qSOFA评分，从SARS-CoV-2时代之前的60名住院成人中进行匹配，作为历史对照。发现：包括61名确诊SARS-CoV-2感染的患者（53名用于结局分析）中，其中21名（40%）在一年康复期内出现了神经学症状。在历史对照队列中，47名随访的患者中，有7名（14%）出现了持续的神经学症状。与对照患者相比，COVID-19患者神经学后遗症的发生年龄更大，病情更严重，包括肝损伤迹象、肾功能下降、白细胞增多和炎症标志物水平升高。与对照相比，COVID-19与神经学后遗症的额外风险相关。与对照患者相比，SARS-CoV-2感染患者的星形胶质纤维蛋白（GFAP）和神经丝轻链（NF-L）显著升高。在调整年龄、性别和疾病严重程度后，GFAP和NF-L与SARS-CoV-2感染患者的长期神经学症状仍显著相关。解释：从急性COVID-19感染中恢复的患者中，相当一部分在住院后一年内发展出神经学后遗症。与历史对照相比，SARS-CoV-2感染患者在住院后一年的随访期间出现神经学症状的可能性更高。与对照患者相比，SARS-CoV-2感染住院患者的血浆GFAP和NF-L水平更高，且与神经学症状相关。