Huang Wei, Li Mei, Luo Guangwei, Wu Xiaojie, Su Bintao, Zhao Lan, Zhang Shuang, Chen Xiaofan, Jia Min, Zhu Jianhua, Su Wen, Zhang Dongxin
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.
J Immunol. 2021 Apr 1;206(7):1597-1608. doi: 10.4049/jimmunol.2001327. Epub 2021 Feb 12.
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.
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。