COVID-19患者在疾病急性期和完全康复后的血浆细胞因子

N. A. Arsentieva, N. Liubimova, O. K. Batsunov, Z. Korobova, O. Stanevich, A. Lebedeva, E. A. Vorobyov, S. V. Vorobyova, A. N. Kulikov, D. Lioznov, M. A. Sharapova, D. Pevtcov, A. Totolian
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引用次数: 10

摘要

新冠肺炎是一种由新型冠状病毒SARS-CoV-2引起的感染,与多种病理生理机制有关,调动了广泛的生物分子,主要是细胞因子。本研究的目的是评估新冠肺炎患者急性期血浆中多种细胞因子的水平,并在完全恢复后检测56名新冠肺炎患者、69名康复者和10名健康人的外周血浆样本中46种分子的浓度,如IL-1α、IL-1β、IL-2、IL-3、IL-4、IL-5、IL-6、IL-7、IL-9、IL-12(p40)、IL-12、p70、IL-13、IL-15、IL-17A/CTLA8、IL-17-E/IL-25、IL-117F、IL-18、IL-22、IL-27、IFNα2、IFNγ、TNFα、TNFβ/淋巴毒素-α(LTA),CCL2/MCP-1、CCL3/MIP-1α、CCL4/MIP-1β、CCL7/MCP-3、CCL11/Eotaxin、CCL22/MDC、CXCL1/GROα、CXCL8/IL-8、CXCL9/MIG、CXCL10/IP-10、CX3CL1/Fractalkine、IL-1ra、IL-10、EGF、FGF-2/FGF碱性、Flt3配体、G-CSF、M-CSF、GM-CSF、PDGF-AA、PDGF-A B/BB、TGF-α,通过xMAP多路复用技术测量VEGF-A在疾病急性期新冠肺炎患者的血浆中发现18种细胞因子水平显著升高(与对照组相比),即IL-6、IL-7、IL-15、IL-27、TNFα、TNFβ/淋巴毒素-α(LTA)、CCL2/MCP-1、CCL7/MCP-3、CXCL1/GROα、CXCL8/IL-8、CXCL10/IP-10、CXCL9/MIG、IL-1r、IL-10、M-CSF、GM-CSF、,VEGF-A我们发现,与患有中度、重度/极重度疾病的患者相比,康复患者中几乎所有提到的细胞因子都显著降低。此外,我们还发现,与对照组相比,康复者血浆中的8种细胞因子水平显著降低,即IL-1α、IL-2、IL-9、IL-12 p40、IL-18、CCL22/MDC、Flt3配体,严重急性呼吸系统综合征冠状病毒2型感染引起的TGF-α免疫反应涉及多种细胞因子,大多具有促炎作用。我们首次表明,恢复期的特点是调节细胞分化和造血的细胞因子水平显著降低(特别是淋巴细胞、T细胞和NK细胞),这些细胞因子的水平没有变化。我们发现,与急性期相比,大多数血浆细胞因子在康复后显著降低。相反,疾病的急性期伴随着血浆中促炎和抗炎细胞因子的显著增加
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Plasma cytokines in patients with COVID-19 during acute phase of the disease and following complete recovery
COVID-19, an infection caused by the new coronavirus SARS-CoV-2, is associated with a number of pathophysiological mechanisms, mobilizing a wide spectrum of biomolecules, mainly, cytokines The purpose of this study was to evaluate levels of multiple cytokines in blood plasma from the patients with COVID-19 during acute phase of the disease, and upon complete recovery Samples of peripheral blood plasma of 56 patients with COVID-19, 69 convalescents and 10 healthy individuals were examined Concentrations of 46 molecules, such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFNα2, IFNγ, TNFα, TNFβ/ Lymphotoxin-α (LTA), CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine, IL-1ra, IL-10, EGF, FGF-2/FGF-basic, Flt3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGF-AB/ BB, TGF-α, VEGF-A were measured via xMAP multiplexing technology Significantly increased levels of 18 cytokines were found in blood plasma from COVID-19 patients during acute phase of the disease (as compared to control group), i e , IL-6, IL-7, IL-15, IL-27, TNFα, TNFβ/Lymphotoxin-α (LTA), CCL2/MCP-1, CCL7/MCP-3, CXCL1/GROα, CXCL8/IL-8, CXCL10/IP-10, CXCL9/MIG, IL-1rа, IL-10, M-CSF, GM-CSF, VEGF-A We found a significant decrease of nearly all the mentioned cytokines in recovered patients, in comparison with those who had moderate, severe/extremely severe disease Moreover, we revealed a significantly decreased level of 8 cytokines in plasma from convalescents, as compared with control group, i e , IL-1α, IL-2, IL-9, IL-12 p40, IL-18, CCL22/MDC, Flt3 Ligand, TGF-α Immune response caused by SARS-CoV-2 infection involves multiple cytokines, mostly, with pro-inflammatory effects We have shown for the first time that the convalescence phase is characterized by significantly lower levels of cytokines which regulate cellular differentiation and hematopoiesis (in particular, lymphocytes, T-cells and NK-cells) Over acute phase of the disease, the levels of these cytokines did not change We revealed a significant decrease of most plasma cytokines upon recovery as compared to acute phase On the contrary, acute phase of the disease is accompanied by significant increase of both pro- and antiinflammatory cytokines in blood plasma
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