Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications

IF 3.7 Q2 IMMUNOLOGY Brain, behavior, & immunity - health Pub Date : 2024-06-13 DOI:10.1016/j.bbih.2024.100805
Fernanda G.Q. Barros-Aragão , Talita P. Pinto , Victor C. Carregari , Nathane B.S. Rezende , Thaís L. Pinheiro , Guilherme Reis-de-Oliveira , Mauro J. Cabral-Castro , Daniel C. Queiroz , Paula L.C. Fonseca , Alessandro L. Gonçalves , Gabriel R. de Freitas , Felipe K. Sudo , Paulo Mattos , Fernando A. Bozza , Erika C. Rodrigues , Renato S. Aguiar , Rosana S. Rodrigues , Carlos O. Brandão , Andrea S. Souza , Daniel Martins-de-Souza , Fernanda Tovar-Moll
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Abstract

COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2's spike protein in patients' CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62–62.23 vs. Mild 3.91 pg/mL CI 1.5–10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4–4.4 vs. Non-Pronounced 2.0, CI 1.4–2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89–123.31 vs Non-Pronounced 6.22, CI 2.9–13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases.

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神经炎症生物标志物的变化与 COVID-19 神经系统并发症患者的疾病严重程度和神经影像学改变相关。
COVID-19 在轻度和重度病例中会诱发急性和持续性神经症状。拟议的伴随机制包括病毒直接感染和变应原、凝血病、缺氧和神经炎症。然而,与轻度和重度病例的多种神经系统结果相关的潜在分子改变却尚未得到深入研究。为了阐明导致 COVID-19 神经系统疾病的可能机制,我们回顾性地详细调查了 35 例 COVID-19 轻度和重度住院患者,这些患者均出现了神经系统改变,并接受了有临床指征的脑脊液(CSF)采样。我们进行了临床和神经系统检查、脑成像、病毒测序和脑脊液分析。我们发现,COVID-19 患者表现出与肺部负担不同的神经症状。鼻拭子病毒测序结果表明,在研究期间,该病毒为优势毒株,而且通过多反应监测分析,我们无法在患者的脑脊液中检测到 SARS-CoV-2 的尖峰蛋白。无论 COVID-19 的严重程度或神经影像学改变如何,患者均表现出全身性炎症和与炎症、先天性免疫和止血相关的 CSF 蛋白质组学的广泛改变。CSF 白细胞介素-6(IL6)升高与疾病严重程度相关(性别、年龄和合并症调整后的平均值:重度 24.5 pg/ml,95% 置信区间 (CI) 9.62-62.23 vs. 轻度 3.91 pg/mL CI 1.5-10.3 患者,p = 0.019)。与无明显神经影像学改变的患者相比,出现明显神经影像学改变的患者的 CSF 肿瘤坏死因子-α(TNFα)和 IL6 水平更高(性别、年龄和合并症调整后的平均 TNFα Pronounced 3.4, CI 2.4-4.4 vs. Non-Pronounced 2.0, CI 1.4-2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89-123.31 vs. Non-Pronounced 6.22, CI 2.9-13.34, p = 0.046)。总之,我们的研究结果表明,神经炎症可能是轻度和重度 COVID-19 急性神经系统疾病的驱动因素。
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来源期刊
Brain, behavior, & immunity - health
Brain, behavior, & immunity - health Biological Psychiatry, Behavioral Neuroscience
CiteScore
8.50
自引率
0.00%
发文量
0
审稿时长
97 days
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