COVID-19 患者外周血淋巴细胞中 DNA 结构的 Labilization

A. Popova, Sergey V. Kuzmin, Natalia A. Ilyushina, Olga V. Gorenskaya, Olga V. Egorova, Alina P. Kotnova, Nataliya S. Averianova, Semen D. Ignatyev, Nataliya E. Kuznetsova, Nataliya V. Kobelevskaya
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Statistical differences between the mean medians of the «%DNA in the comet tail» (tail DNA%) were assessed using Student’s t-test. The Jeffers test was used to compare the proportions of cells with different levels of DNA-damage. Statistical differences between groups were assessed using the Mann-Whitney test. \nResults. In the COVID-19 patients, an increase in the level of breaks and alkali-labile sites in DNA was revealed when compared to controls (p = 0.025). \nIn the group of patients infected with SARS-CoV-2, the proportion of comets with DNA damage of up to 5% decreased (p = 0.009), while the proportion of comets containing more than 10% DNA tail increased (p = 0.000). The number of atypical comets compared to the control increased by 3.7 and 5.9 times with mild and moderate severity of the disease, respectively (r = 0.993; p = 0.001). 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摘要

引言现有数据表明,SARS-CoV-2 冠状病毒可损害 DNA 修复过程,造成氧化应激,从而导致人体细胞内 DNA 损伤的累积。然而,人们对该病毒的 DNA 损伤作用尚未进行充分研究。本研究旨在研究 SARS-CoV-2 在人类外周血淋巴细胞中造成 DNA 损伤的能力。材料和方法。研究对象包括 140 名 COVID-19 患者和 24 名对照组供体。淋巴细胞中的 DNA 碎片水平通过碱性 DNA-Comet 分析法测定。采用学生 t 检验法评估 "彗尾 DNA%"(彗尾 DNA%)平均中值之间的统计差异。Jeffers 检验用于比较不同 DNA 损伤程度的细胞比例。组间统计差异采用 Mann-Whitney 检验。结果与对照组相比,COVID-19 患者 DNA 的断裂和碱溶性位点增加(p = 0.025)。在感染SARS-CoV-2的患者组中,DNA损伤不超过5%的彗星比例下降(p = 0.009),而DNA尾部超过10%的彗星比例上升(p = 0.000)。与对照组相比,病情轻度和中度的非典型彗星数量分别增加了 3.7 倍和 5.9 倍(r = 0.993;p = 0.001)。在与冠心病(CHD)和二型糖尿病(DM 2 型)相关的疾病中,与无这些疾病的患者组相比,淋巴细胞中 DNA 碎片的水平在统计学上显著增加。局限性。缺乏有关严重 COVID-19 疾病中 DNA 结构损伤的数据。结论。SARS-CoV-2感染会导致人体外周血淋巴细胞中的DNA结构变色。DNA 损伤程度取决于 COVID-19 的严重程度以及是否存在合并疾病:心脏病和 2 型糖尿病。研究结果对于了解病毒对人类免疫功能健全细胞的作用机制非常重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Labilization of the DNA structure in peripheral blood lymphocytes of COVID-19 patients
Introduction. Available data indicate the SARS-CoV-2 coronavirus to be potent of impairing DNA repair processes and cause oxidative stress, which can lead to the accumulation of DNA damage in human cells. However, the DNA-damaging effect of the virus has not yet been sufficiently studied. The purpose of the research was to study the ability of SARS-CoV-2 to cause DNA damage in human peripheral blood lymphocytes. Materials and methods. One hundred forty COVID-19 patients and 24 donors of the control group are included in the study. The level of DNA fragmentation in lymphocytes was determined by alkaline DNA-comet assay. Statistical differences between the mean medians of the «%DNA in the comet tail» (tail DNA%) were assessed using Student’s t-test. The Jeffers test was used to compare the proportions of cells with different levels of DNA-damage. Statistical differences between groups were assessed using the Mann-Whitney test. Results. In the COVID-19 patients, an increase in the level of breaks and alkali-labile sites in DNA was revealed when compared to controls (p = 0.025). In the group of patients infected with SARS-CoV-2, the proportion of comets with DNA damage of up to 5% decreased (p = 0.009), while the proportion of comets containing more than 10% DNA tail increased (p = 0.000). The number of atypical comets compared to the control increased by 3.7 and 5.9 times with mild and moderate severity of the disease, respectively (r = 0.993; p = 0.001). In the association with diseases – coronary heart disease (CHD) and diabetes mellitus type II (DM type 2), the level of DNA fragmentation in lymphocytes statistically significantly increased compared to the group of patients without these diseases. Limitations. A limitation is the lack of data on DNA-structure damage in severe COVID-19 disease. Conclusion. SARS-CoV-2 infection leads to labilization of the DNA structure in human peripheral blood lymphocytes. The level of DNA damage depends on the severity of COVID-19 and the presence of comorbid diseases: CHD and DM type 2. The results of the study are important for understanding the mechanisms of action of the virus on human immunocompetent cells.
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