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与疾病严重程度相关的炎症因子预测COVID-19病情进展

The Inflammatory Factors Associated with Disease Severity to Predict COVID-19 Progression.

作者信息

Huang Wei, Li Mei, Luo Guangwei, Wu Xiaojie, Su Bintao, Zhao Lan, Zhang Shuang, Chen Xiaofan, Jia Min, Zhu Jianhua, Su Wen, Zhang Dongxin

机构信息

Department of Laboratory Medicine, Wuhan No. 1 Hospital, Wuhan 430022, People's Republic of China.

Department of Respiratory and Critical Care Medicine, Wuhan No. 1 Hospital, Wuhan 430022, People's Republic of China.

出版信息

J Immunol. 2021 Apr 1;206(7):1597-1608. doi: 10.4049/jimmunol.2001327. Epub 2021 Feb 12.

Abstract

Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. Exploring the immune-inflammatory characteristics of COVID-19 patients is essential to reveal pathogenesis and predict progression. In this study, COVID-19 patients showed decreased CD3, CD4, and CD8 T cells but increased neutrophils in circulation, exhibiting upregulated neutrophil-to-lymphocyte and neutrophil-to-CD8 T cell ratio. IL-6, TNF-α, IL-1β, IL-18, IL-12/IL-23p40, IL-10, Tim-3, IL-8, neutrophil extracellular trap-related proteinase 3, and S100A8/A9 were elevated, whereas IFN-γ and C-type lectin domain family 9 member A (clec9A) were decreased in COVID-19 patients compared with healthy controls. When compared with influenza patients, the expressions of TNF-α, IL-18, IL-12/IL-23p40, IL-8, S100A8/A9 and Tim-3 were significantly increased in critical COVID-19 patients, and carcinoembryonic Ag, IL-8, and S100A8/A9 could serve as clinically available hematologic indexes for identifying COVID-19 from influenza. Moreover, IL-6, IL-8, IL-1β, TNF-α, proteinase 3, and S100A8/A9 were increased in bronchoalveolar lavage fluid of severe/critical patients compared with moderate patients, despite decreased CD4 T cells, CD8 T cells, B cells, and NK cells. Interestingly, bronchoalveolar IL-6, carcinoembryonic Ag, IL-8, S100A8/A9, and proteinase 3 were found to be predictive of COVID-19 severity and may serve as potential biomarkers for predicting COVID-19 progression and potential targets in therapeutic intervention of COVID-19.

摘要

2019冠状病毒病(COVID-19)与免疫失调和细胞因子风暴有关。探索COVID-19患者的免疫炎症特征对于揭示发病机制和预测病情进展至关重要。在本研究中,COVID-19患者循环中的CD3、CD4和CD8 T细胞减少,但中性粒细胞增多,中性粒细胞与淋巴细胞以及中性粒细胞与CD8 T细胞的比例上调。与健康对照相比,COVID-19患者的IL-6、TNF-α、IL-1β、IL-18、IL-12/IL-23p40、IL-10、Tim-3、IL-8、中性粒细胞胞外诱捕网相关蛋白酶3和S100A8/A9升高,而IFN-γ和C型凝集素结构域家族9成员A(clec9A)降低。与流感患者相比,重症COVID-19患者中TNF-α、IL-18、IL-12/IL-23p40、IL-8、S100A8/A9和Tim-3的表达显著增加,癌胚抗原、IL-8和S100A8/A9可作为从流感中鉴别COVID-19的临床可用血液学指标。此外,与中度患者相比,重症/危重症患者支气管肺泡灌洗液中的IL-6、IL-8、IL-1β、TNF-α、蛋白酶3和S100A8/A9增加,尽管CD4 T细胞、CD8 T细胞、B细胞和NK细胞减少。有趣的是,发现支气管肺泡IL-6、癌胚抗原、IL-8、S1'00A8/A9和蛋白酶3可预测COVID-19的严重程度,并可能作为预测COVID-19病情进展的潜在生物标志物以及COVID-19治疗干预的潜在靶点。

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