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COVID-19 患者疾病严重程度表现相关促炎分子的相对表达。

Relative expression of proinflammatory molecules in COVID-19 patients who manifested disease severities.

机构信息

Department of Nutrition and Food Technology, Jashore University of Science and Technology, Jashore, Bangladesh.

Department of Microbiology, University of Dhaka, Dhaka, Bangladesh.

出版信息

J Med Virol. 2021 Oct;93(10):5805-5815. doi: 10.1002/jmv.27112. Epub 2021 Jun 12.

Abstract

Aggressive immune response, due to overexpressed proinflammatory molecules, has been characterized in coronavirus disease 2019 (COVID-19) patients. Some of those mediators have a dual and opposite role on immune systems at play behind differential disease severities. We investigated the expression of some cytokines and chemokines in COVID-19 patients in Bangladesh. We diagnosed the patients by detecting severe acute respiratory syndrome coronavirus 2 RNA in nasal swab samples by the real-time RT-PCR method. Thirty adult patients were preselected based on their disease severities and grouped into mild, moderate, and severe cases. Nine healthy volunteers participated in this study as a control. Relative expression of nine cytokines/chemokine in total leukocytes was semi-quantified in SYBRgreen-based real-time quantitative reverse-transcriptase polymerase chain reaction. We performed statistical tests on transformed log data using SPSS 24.0. At the onset of symptoms (Day 1), angiotensin-converting enzyme 2 (ACE2) (p < 0.05) and interleukin (IL)-6 (p > 0.05) were upregulated in all COVID-19 groups, although the expression levels did not significantly correlate with disease severities. However, expressions of IL-6, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, tumor necrosis factor-α (TNF-α), RANTES (regulated upon activation, normal T cell expressed and secreted), and ACE2, on Day 14, were positively correlated with disease severities. Relative viral load at Day 1 showed no significant correlation with cytokine expression but had a significant positive correlation with RANTES and ACE2 expression on Day 14 (p < 0.05). Male patients had a higher level of IL-6 than female patients on Day 1 (p < 0.05). All COVID-19 patients showed upregulated cytokines and chemokines on Day 14 compared to Day 1 except TNF-α. Female patients had a higher expression of ACE2 and IL-12 on Day 14. Upregulated cytokines/chemokines at the convalescent stage, especially IL-6, may help in targeting anticytokine therapy in post-COVID-19 patients' management.

摘要

在 2019 年冠状病毒病(COVID-19)患者中,过度表达的前炎症分子导致了强烈的免疫反应。这些介质中的一些在不同疾病严重程度背后的免疫系统中发挥着双重相反的作用。我们在孟加拉国调查了 COVID-19 患者的一些细胞因子和趋化因子的表达情况。我们通过实时 RT-PCR 方法检测鼻拭子样本中的严重急性呼吸综合征冠状病毒 2 RNA 来诊断患者。根据疾病严重程度预选了 30 名成年患者,并将其分为轻症、中度和重症病例。9 名健康志愿者作为对照参加了这项研究。在 SYBRgreen 基础上的实时定量逆转录聚合酶链反应中,半定量测定了白细胞中 9 种细胞因子/趋化因子的相对表达。我们使用 SPSS 24.0 对转换后的对数数据进行了统计检验。在症状出现的第一天(第 1 天),所有 COVID-19 组的血管紧张素转换酶 2(ACE2)(p<0.05)和白细胞介素(IL)-6(p>0.05)均上调,尽管表达水平与疾病严重程度没有显著相关性。然而,第 14 天时,IL-6、单核细胞趋化蛋白-1、巨噬细胞炎症蛋白-1α、肿瘤坏死因子-α(TNF-α)、RANTES(激活正常 T 细胞表达和分泌)和 ACE2 的表达与疾病严重程度呈正相关。第 1 天的相对病毒载量与细胞因子表达无显著相关性,但与第 14 天的 RANTES 和 ACE2 表达呈显著正相关(p<0.05)。第 1 天,男性患者的 IL-6 水平高于女性患者(p<0.05)。与第 1 天相比,所有 COVID-19 患者在第 14 天的细胞因子和趋化因子均上调,除 TNF-α外。第 14 天,女性患者的 ACE2 和 IL-12 表达水平较高。恢复期上调的细胞因子/趋化因子,特别是 IL-6,可能有助于针对 COVID-19 患者管理中的抗细胞因子治疗。

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