Hirzel Cédric, Grandgirard Denis, Surial Bernard, Wider Manon F, Leppert David, Kuhle Jens, Walti Laura N, Schefold Joerg C, Spinetti Thibaud, Suter-Riniker Franziska, Dijkman Ronald, Leib Stephen L
Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
Ther Adv Neurol Disord. 2022 Mar 12;15:17562864221080528. doi: 10.1177/17562864221080528. eCollection 2022.
In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune response with regard to neuronal injury has not yet been investigated.
In a prospective cohort study, we recruited patients with mild-moderate ( = 39) and severe ( = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses.
sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild-moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild-moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies.
Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels.
在2019冠状病毒病（COVID-19）患者中，越来越多的证据表明血清神经丝轻链（sNfL）水平升高意味着存在神经元损伤。然而，全身炎症和严重急性呼吸综合征冠状病毒2（SARS-CoV-2）特异性免疫反应在神经元损伤方面的作用尚未得到研究。
在一项前瞻性队列研究中，我们招募了轻度至中度（n = 39）和重度（n = 14）COVID-19患者，并在入组时和28（±7）天时测量了sNfL水平、细胞因子浓度、包括中和抗体滴度在内的SARS-CoV-2特异性抗体以及细胞介导的免疫反应。我们通过sNfL测量来探究神经轴突损伤与疾病严重程度、细胞因子水平和病毒特异性免疫反应之间的关联。
作为神经元损伤指标的sNfL水平在入组时较高，且在重症患者的随访期间有所升高，而在轻度至中度COVID-19期间，sNfL水平保持不变。与轻度至中度疾病相比，重度COVID-19与所评估的细胞因子[白细胞介素（IL）-6、IL-8、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）]浓度升高、抗刺突IgG和抗核衣壳IgG浓度升高以及中和抗体滴度升高有关。病情更严重的患者具有更高数量的明确的SARS-CoV-2特异性T细胞。从基线到第28（±7）天sNfL浓度的增加与抗刺突蛋白IgG抗体水平和中和抗体滴度呈正相关。
重度COVID-19与细胞因子血清浓度升高以及随后的神经元损伤相关，这通过sNfL水平升高得以体现。在COVID-19病程中，病情更严重的患者产生了更高的中和抗体滴度和更高数量的SARS-CoV-2特异性T细胞。在SARS-CoV-2感染后产生明显的病毒特异性体液和细胞介导免疫反应并不能防止通过sNfL水平所反映的神经轴突损伤。
