Bae Gyuntae, Yang Zhiqi, Bucci Daniele, Wegner Claire, Schäfer Hartmut, Singh Yogesh, Lonati Caterina, Trautwein Christoph
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tübingen, Tübingen, Germany.
Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.
Metabolomics. 2025 May 7;21(3):65. doi: 10.1007/s11306-025-02262-y.
Individuals suffering from acute COVID-19 (AC) often develop long COVID-19 (LC) syndrome that is associated with aberrant levels of lipoproteins and inflammatory mediators. Yet, these dysregulations are heterogenous due to the uncertain prevalence and require a more extensive characterization.
This study aimed to investigate LC-associated dysregulations in inflammatory mediators and lipids by longitudinal Nuclear Magnetic Resonance (NMR) lipoprotein analysis and cytokine profiling in human blood.
We quantitatively profiled lipoproteins and inflammatory parameters in LC patients at 5 (n = 95), 9 (n = 73), 12 (n = 95), 16 (n = 78), and 20 (n = 85) months post AC by in vitro diagnostics research (IVDr)-based NMR spectroscopy. Simultaneously, we assessed inflammatory meditators with a 13-plex cytokine panel by flow cytometry. We then compared the lipoprotein profiles with historical data from AC (N = 307) and healthy cohorts collected before the COVID-19 pandemic (N = 305), whereas the cytokine profiles were correlated with that of the AC cohort.
We identified 31 main and 80 significantly altered subclass lipoproteins, respectively. LC was associated with higher serum levels of very low-density, intermediate-density, low-density, high-density lipoproteins, along with triglycerides, cholesterols, and apolipoprotein a-I & a-II lipoproteins compared to the healthy cohort. We also observed significantly lower concentrations of NMR-based inflammatory parameters in LC than in AC cohort, whilst proinflammatory mediators IFN-α2, IFN-γ, TNF-α, CXCL8/IL-8, IL-12p70, IL-17 A, and IL-23 displayed significantly higher concentrations in LC compared with the AC cohort. Conversely, CCL2/MCP-1, IL-6, and IL-18 were significantly higher in the AC cohort than in LC.
Our findings demonstrate a persistent hyperlipidemic phenotype in LC alongside signs of chronic inflammation and lipoprotein metabolism that vary in states of acute and chronic inflammation.
患有急性新冠病毒感染（AC）的个体常发展为新冠后综合征（LC），这与脂蛋白和炎症介质水平异常有关。然而，由于患病率不确定，这些失调情况存在异质性，需要更广泛的特征描述。
本研究旨在通过纵向核磁共振（NMR）脂蛋白分析和人血中细胞因子谱分析，调查LC相关的炎症介质和脂质失调情况。
我们通过基于体外诊断研究（IVDr）的NMR光谱法，对AC后5个月（n = 95）、9个月（n = 73）、12个月（n = 95）、16个月（n = 78）和20个月（n = 85）的LC患者的脂蛋白和炎症参数进行了定量分析。同时，我们通过流式细胞术用13重细胞因子检测板评估炎症介质。然后，我们将脂蛋白谱与AC的历史数据（N = 307）以及新冠疫情大流行前收集的健康队列数据（N = 305）进行比较，而细胞因子谱则与AC队列的谱进行相关性分析。
我们分别确定了31种主要和80种显著改变的亚类脂蛋白。与健康队列相比，LC与极低密度脂蛋白、中间密度脂蛋白、低密度脂蛋白、高密度脂蛋白以及甘油三酯、胆固醇和载脂蛋白a-I及a-II脂蛋白的血清水平升高有关。我们还观察到，LC中基于NMR的炎症参数浓度明显低于AC队列，而促炎介质IFN-α2、IFN-γ、TNF-α、CXCL8/IL-8、IL-12p70、IL-17 A和IL-23在LC中的浓度明显高于AC队列。相反，CCL2/MCP-1、IL-6和IL-18在AC队列中明显高于LC。
我们的研究结果表明，LC存在持续的高脂血症表型，同时伴有慢性炎症和脂蛋白代谢的迹象，这些在急性和慢性炎症状态下有所不同。
