与 COVID-19 相关的脊髓炎:临床、放射学和实验室特征

Aleksandra Kozlova, Alina Dzharullaeva, Amir Tukhvatulin, I. Zakroyshchikova, T. Simaniv, Lola Askarova, D. Eliseeva, Natalia Stoida, I. Kochergin, E. Baydina, M. Zakharova
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CSF from patients with myelitis associated with COVID-19 (11 patients) was compared with CSF of healthy controls (HC) (7 patients) and patients with MS (37 patients) from the non-COVID era. CSF cytological examination, protein levels and oligoclonal bands (OCBs) evaluation, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus detection and cytokine profiling using Bio-Plex Pro Human Inflammation Panel 1, 37-Plex were performed.\nResults: In total 11 patients with different types of myelitis developed up to 3 months after COVID-19 were enrolled in the study. Radiological findings were diverse: short transverse myelitis (lesion of fewer than 3 segments) (n = 6), longitudinal extensive transverse myelitis (LETM) (n = 2), multifocal spinal cord lesions (n = 1), and myelitis involving dorsal and lateral columns (n = 2). 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引用次数: 0

摘要

目的:本研究旨在描述与新型冠状病毒感染[冠状病毒病2019(COVID-19)]相关的各种类型的脊髓炎,分析受影响患者的细胞因子谱和脑脊液(CSF)参数,并将其与其他免疫介导疾病-多发性硬化症(MS)患者进行比较,以确定可能的共同致病途径,从而确定治疗目标:方法:根据患者病史研究其临床、放射学和实验室特征。将与 COVID-19 相关的脊髓炎患者(11 例)的脑脊液与健康对照组(7 例)和非 COVID 时代的多发性硬化症患者(37 例)的脑脊液进行比较。研究人员还进行了脑脊液细胞学检查、蛋白质水平和寡克隆带(OCBs)评估、严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)病毒检测,并使用 Bio-Plex Pro Human Inflammation Panel 1, 37-Plex 进行了细胞因子分析:共有 11 名患者在 COVID-19 后 3 个月内患上了不同类型的脊髓炎。放射学检查结果多种多样:短横贯性脊髓炎(病变少于 3 节)(6 例)、纵向广泛横贯性脊髓炎(2 例)、多灶性脊髓病变(1 例)以及累及背侧柱和侧柱的脊髓炎(2 例)。部分横贯性脊髓炎患者和抗髓鞘少突胶质细胞糖蛋白(MOG)抗体(MOG 抗体)患者对治疗的反应最为明显。多项比较显示,与 MS 组相比,COVID-19 骨髓炎(CM)患者的白细胞介素-10(IL-10)、干扰素-α2(IFN-α2)、IFN-β 和胸腺基质淋巴细胞生成素(TSLP)水平降低,IL-19 和 B 细胞活化因子(BAFF)水平升高。BAFF和增殖诱导配体(APRIL)浓度最高的患者神经系统残疾程度最严重:结论:与COVID-19相关的脊髓炎在临床和影像学上具有异质性。对 COVID-19 相关性脊髓炎患者的细胞因子谱进行评估后发现,除少数细胞因子外,它们与多发性硬化症患者的细胞因子谱相对相似。BAFF/APRIL系统和IL-10在自身免疫性疾病的发生和发展中的作用众所周知,然而,它们与COVID-19的联系以及对SARS-CoV-2后免疫介导的中枢神经系统(CNS)疾病发生的影响仍有待进一步研究。
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Myelitis associated with COVID-19: clinical, radiological, and laboratory characteristics
Aim: The current study aimed to describe various types of myelitis associated with a novel coronavirus infection [coronavirus disease 2019 (COVID-19)] as well as to analyze cytokine profiles and cerebrospinal fluid (CSF) parameters in affected patients and to compare them to patients with other immune-mediated disorders—multiple sclerosis (MS), in order to identify possible common pathogenetic pathways and consequently treatment targets. Methods: Clinical, radiological, and laboratory characteristics were studied based on patients’ history. CSF from patients with myelitis associated with COVID-19 (11 patients) was compared with CSF of healthy controls (HC) (7 patients) and patients with MS (37 patients) from the non-COVID era. CSF cytological examination, protein levels and oligoclonal bands (OCBs) evaluation, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus detection and cytokine profiling using Bio-Plex Pro Human Inflammation Panel 1, 37-Plex were performed. Results: In total 11 patients with different types of myelitis developed up to 3 months after COVID-19 were enrolled in the study. Radiological findings were diverse: short transverse myelitis (lesion of fewer than 3 segments) (n = 6), longitudinal extensive transverse myelitis (LETM) (n = 2), multifocal spinal cord lesions (n = 1), and myelitis involving dorsal and lateral columns (n = 2). The most pronounced response to treatment was observed in patients with partial transverse myelitis and patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG Abs). Multiple comparisons have demonstrated decreased levels of interleukin-10 (IL-10), interferon-α2 (IFN-α2), IFN-β, and thymic stromal lymphopoietin (TSLP), and increased IL-19 and B cell activating factor (BAFF) in patients with COVID-19 myelitis (CM) compared to the MS group. The highest BAFF and a proliferation-inducing ligand (APRIL) concentrations were found in patients with the most profound neurological disability. Conclusions: Myelitis associated with COVID-19 is clinically and radiologically heterogeneous. Evaluation of cytokine profiles in patients with myelitis associated with COVID-19 revealed their relative similarity with ones of MS patients, except for a few cytokines. BAFF/APRIL system as well as IL-10 is well-known for the role in the development and progression of autoimmune diseases, however, their links with COVID-19 and effects on the development of immune-mediated central nervous system (CNS) disorders after SARS-CoV-2 remain to be further studied.
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