Plasma proteomics show altered inflammatory and mitochondrial proteins in patients with neurologic symptoms of post-acute sequelae of SARS-CoV-2 infection.
Plasma proteomics show altered inflammatory and mitochondrial proteins in patients with neurologic symptoms of post-acute sequelae of SARS-CoV-2 infection.
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血浆蛋白质组学显示，患有 SARS-CoV-2 感染急性后遗症的神经系统症状的患者的炎症和线粒体蛋白发生了改变。
DOI：
10.1016/j.bbi.2023.08.022
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Koralnik,IgorJ
中科院分区：
文献类型：
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作者：
Hanson,BarbaraA;Visvabharathy,Lavanya;Orban,ZacharyS;Jimenez,Millenia;Batra,Ayush;Liotta,EricM;DeLisle,RobertK;Klausner,JeffreyD;Cohen,Pinchas;Padhye,AdvaitS;Tachas,George;Koralnik,IgorJ
COVID-19幸存者的持续症状构成长期COVID综合征，也称为SARS-CoV-2感染后急性后遗症（PASC）。PASC（Neuro-PASC）的神经系统表现特别使人衰弱，持续时间长，且了解不多。为了深入了解PASC的发病机制，我们利用了在我们的Neuro-COVID-19诊所看到的一组特征良好的Neuro-PASC（NP）患者，他们患有轻度急性COVID-19，从未需要住院治疗，以研究他们的血浆蛋白质组。使用SomaLogic平台SomaScan，从92名未接种疫苗的个体中测量>7000种蛋白质的血浆浓度，包括48名NP患者，20名没有持续症状的COVID-19恢复期（CC）和24名未暴露的健康对照（HC），以询问PASC的潜在病理生物学和潜在生物标志物。我们基于COVID-19后状态、神经系统和非神经系统症状，以及与Neuro-PASC相关的生活质量（QoL）和认知变化的主观和客观标准化测试，分析了血浆蛋白质组。NP患者的血浆蛋白质组与CC和HC受试者的差异比COVID-19后组（NP和CC合并）与HC的差异更大。急性COVID-19后3-9个月NP患者的蛋白质组差异显示，相对于CC和HC受试者，炎症蛋白和通路发生了改变。与脑雾和疲劳的神经PASC症状相关的蛋白质组学包括DNA修复、氧化应激和中性粒细胞脱粒标志物的变化。此外，我们发现NP患者恢复到COVID-19前基线的主观印象较低与氧化磷酸化蛋白COX 7A 1浓度增加之间存在相关性，这也与神经系统症状和疲劳以及QoL和认知功能障碍受损相关。最后，我们确定了其他与中枢神经系统症状相关的氧化磷酸化相关蛋白。我们的研究结果表明Neuro-PASC中正在发生的炎症变化和线粒体参与，并为生物标志物验证铺平了道路，用于监测和开发这种衰弱疾病的治疗干预。
Persistent symptoms of COVID-19 survivors constitute long COVID syndrome, also called post-acute sequelae of SARS-CoV-2 infection (PASC). Neurologic manifestations of PASC (Neuro-PASC) are particularly debilitating, long lasting, and poorly understood. To gain insight into the pathogenesis of PASC, we leveraged a well-characterized group of Neuro-PASC (NP) patients seen at our Neuro-COVID-19 clinic who had mild acute COVID-19 and never required hospitalization to investigate their plasma proteome. Using the SomaLogic platform, SomaScan, the plasma concentration of >7000 proteins was measured from 92 unvaccinated individuals, including 48 NP patients, 20 COVID-19 convalescents (CC) without lingering symptoms, and 24 unexposed healthy controls (HC) to interrogate underlying pathobiology and potential biomarkers of PASC. We analyzed the plasma proteome based on post-COVID-19 status, neurologic and non-neurologic symptoms, as well as subjective and objective standardized tests for changes in quality-of-life (QoL) and cognition associated with Neuro-PASC. The plasma proteome of NP patients differed from CC and HC subjects more substantially than post-COVID-19 groups (NP and CC combined) differed from HC. Proteomic differences in NP patients 3–9 months following acute COVID-19 showed alterations in inflammatory proteins and pathways relative to CC and HC subjects. Proteomic associations with Neuro-PASC symptoms of brain fog and fatigue included changes in markers of DNA repair, oxidative stress, and neutrophil degranulation. Furthermore, we discovered a correlation between NP patients lower subjective impression of recovery to pre-COVID-19 baseline with an increase in the concentration of the oxidative phosphorylation protein COX7A1, which was also associated with neurologic symptoms and fatigue, as well as impairment in QoL and cognitive dysfunction. Finally, we identified other oxidative phosphorylation-associated proteins correlating with central nervous system symptoms. Our results suggest ongoing inflammatory changes and mitochondrial involvement in Neuro-PASC and pave the way for biomarker validation for use in monitoring and development of therapeutic intervention for this debilitating condition.