Cheng Jianghao, Wang Haozhen, Li Chaodan, Yu Jianhua, Zhu Mingli
Department of Open Laboratory Medicine, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Department of General Practice, Jinhua People's Hospital, Jinhua, China.
Front Immunol. 2024 Nov 25;15:1464545. doi: 10.3389/fimmu.2024.1464545. eCollection 2024.
Cytokines and chemokines as crucial participants in innate immune response play significant roles during SARS-CoV-2 infection, yet excessive immune response exacerbates the severity of COVID-19.
This study aims to investigate the involvement of which cytokines/chemokines in the cytokine storm of COVID-19, as well as the changes in cytokine/chemokine levels during the course of COVID-19, simultaneously exploring the diagnostic and prognostic value of the relevant cytokines/chemokines for COVID-19.
Flow cytometry was employed to detect the levels of cytokines and chemokines in the serum of 50 COVID-19 patients.
Compared with severe COVID-19 patients, the levels of cytokines IL-6, IL-8, IL-10, sCD25, and chemokines IP-10 and MIG in the peripheral blood of non-severe patients were significantly reduced, while only IL-6, IL-10, and IP-10 levels were significantly decreased compared to non-survivors of COVID-19. Meanwhile, serum concentrations of IP-10, MCP-1, sTREM-1, IL-10, and the neutrophil-to-lymphocyte ratio (NLR) in peripheral blood could distinguish between COVID-19 survivors and non-survivors and were significantly associated with mortality. Among them, the concentration of IP-10 was shown to be the most powerful indicator for predicting adverse outcomes in COVID-19 patients (AUC: 0.715); however, its combined detection with the conventional inflammatory marker NLR did not improve the predictive value for adverse outcomes in COVID-19 patients. Additionally, serum IP-10 levels were negatively correlated with peripheral blood NK cell count and total lymphocyte count, while sTREM-1 levels were positively correlated with peripheral blood CD4+ T cell count and CD3+ T cell count. Meanwhile, IL-8 levels were positively correlated with total lymphocyte count in peripheral blood. Finally, the serum levels of cytokines/chemokines in non-survivors of COVID-19 increased significantly before death, while in survivors, they returned to normal levels before discharge.
Severely ill and non-surviving COVID-19 patients exhibit compromised immune function, with significantly higher levels of inflammation, cytokine/chemokine storms, and immune dysregulation compared to non-severe patients. Serum concentrations of IP-10, MCP-1, sTREM-1, and IL-10 levels can serve as biomarkers to predict adverse outcomes in COVID-19.
细胞因子和趋化因子作为先天免疫反应的关键参与者，在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染过程中发挥重要作用，但过度的免疫反应会加剧冠状病毒病2019（COVID-19）的严重程度。
本研究旨在探讨哪些细胞因子/趋化因子参与了COVID-19的细胞因子风暴，以及COVID-19病程中细胞因子/趋化因子水平的变化，同时探索相关细胞因子/趋化因子对COVID-19的诊断和预后价值。
采用流式细胞术检测50例COVID-19患者血清中的细胞因子和趋化因子水平。
与重症COVID-19患者相比，非重症患者外周血中细胞因子白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、可溶性白细胞介素-2受体α链（sCD25）以及趋化因子干扰素诱导蛋白10（IP-10）和巨噬细胞炎性蛋白诱导基因（MIG）水平显著降低，而与COVID-19非幸存者相比，只有IL-6、IL-10和IP-10水平显著下降。同时，外周血中IP-10、单核细胞趋化蛋白-1（MCP-1）、可溶性髓系细胞触发受体-1（sTREM-1）、IL-10的血清浓度以及中性粒细胞与淋巴细胞比值（NLR）可区分COVID-19幸存者和非幸存者，且与死亡率显著相关。其中，IP-10浓度被证明是预测COVID-19患者不良结局的最有力指标（曲线下面积：0.715）；然而，其与传统炎症标志物NLR联合检测并未提高对COVID-19患者不良结局的预测价值。此外，血清IP-10水平与外周血自然杀伤（NK）细胞计数和总淋巴细胞计数呈负相关，而sTREM-1水平与外周血CD4 + T细胞计数和CD3 + T细胞计数呈正相关。同时，IL-8水平与外周血总淋巴细胞计数呈正相关。最后，COVID-19非幸存者血清中细胞因子/趋化因子水平在死亡前显著升高，而幸存者在出院前恢复至正常水平。
重症和死亡的COVID-19患者免疫功能受损，与非重症患者相比，炎症水平、细胞因子/趋化因子风暴和免疫失调显著更高。血清中IP-10、MCP-1、sTREM-1和IL-10水平可作为预测COVID-19不良结局的生物标志物。
