Department of Molecular Biology and Biotechnology, V.N. Karazin National University, 4 Pl. Svobody, 61022 Kharkiv, Ukraine; Diagnostic Laboratory with Enzyme Immunoassay and Immunofluorescence Analysis, State Institution "Zaycev V.T. Institute of General and Urgent Surgery of National Academy of Medical Sciences of Ukraine", Balakireva vyizd, 1, 61103 Kharkiv, Ukraine.
Department of Molecular Biology and Biotechnology, V.N. Karazin National University, 4 Pl. Svobody, 61022 Kharkiv, Ukraine.
Immunobiology. 2023 Jan;228(1):152316. doi: 10.1016/j.imbio.2022.152316. Epub 2022 Dec 20.
We studied the role of cytotoxic components (DAMPs) formed in the body of patients with COVID-19 in ensuring the long-term preservation of post-COVID-19 manifestations and the possibility of creating an experimental model by transferring DAMPs to rats. In patients with post-COVID-19 syndrome (PCS) 2 months after SARS-CoV-2 infection we determined the presence of cytotoxic components in the blood serum (Terasaki test, Dunaliella viridis test and content of DAMPs). In post-COVID-19 syndrome patients with a high content of serum cytotoxic oligopeptide fraction (selective group, n = 16) we determined the number of leukocytes, lymphocytes, neutrophil granulocytes and monocytes in the blood, the content of C-reactive protein (CRP), the concentration of C3 and C4 complement components and circulating immune complexes, the serum content of IL-6, IL -10, IL-18, TNF-α, phagocytic activity of neutrophils, presence of neutrophil traps and autoantibodies ANA. It has been shown that in patients with PCS, there are components with cytotoxicity in the blood serum, form specific immunopathological patterns, which are characterized by: an increased content of CRP, complement system components C3 and C4 and cytokines (TNF-α, IL-6, IL-10, IL-18) activation, the formation of a wide range of autoantibodies ANA, the low efficiency of endocytosis in oxygen-independent phagocytosis; their phagocytic activity reaches its functional limit, and against this background, activation of neutrophil traps occurs, which can contribute to further induction of DAMPs. This self-sustaining cell-killing activation provided long-term preservation of PCS symptoms. The transfer of blood serum components from selective group patients with PCS to rats was accompanied by the appearance of cytotoxic components in them which induced sensitization and immunopathological reactions. Preventive administration of a biologically active substance with polyfunctional properties MF to experimental animals "corrected" the initial functional state of the body's immune-metabolic system and eliminated or facilitated immuno-inflammatory reactions.
我们研究了 COVID-19 患者体内形成的细胞毒性成分(DAMPs)在确保 COVID-19 后表现长期存在方面的作用,以及通过将 DAMPs 转移到大鼠身上来创建实验模型的可能性。在 SARS-CoV-2 感染后 2 个月患有 COVID-19 后综合征(PCS)的患者中,我们确定了血清(Terasaki 试验、杜氏盐藻试验和 DAMPs 含量)中细胞毒性成分的存在。在 PCS 患者的血清中存在高浓度的细胞毒性寡肽片段(选择性组,n=16)的情况下,我们确定了白细胞、淋巴细胞、中性粒细胞和单核细胞的数量、C-反应蛋白(CRP)的含量、C3 和 C4 补体成分的浓度和循环免疫复合物、血清中 IL-6、IL-10、IL-18、TNF-α、中性粒细胞吞噬活性、中性粒细胞陷阱和自身抗体 ANA 的含量。结果表明,在 PCS 患者中,血清中存在具有细胞毒性的成分,形成特定的免疫病理模式,其特征为:CRP、补体系统成分 C3 和 C4 以及细胞因子(TNF-α、IL-6、IL-10、IL-18)的含量增加,形成广泛的自身抗体 ANA,在缺氧非依赖性吞噬作用中内吞作用效率低下;其吞噬活性达到功能极限,在此背景下,中性粒细胞陷阱被激活,这可能有助于进一步诱导 DAMPs。这种自我维持的细胞杀伤激活提供了 PCS 症状的长期存在。将来自选择性 PCS 患者的血清成分转移到大鼠身上,会导致它们出现细胞毒性成分,从而引发致敏和免疫病理反应。预防性给予具有多功能特性的生物活性物质 MF 可纠正实验动物初始的免疫代谢系统功能状态,并消除或促进免疫炎症反应。