Fan Qinghong, Deng Kai, Huang Huang, He Ruiying, Deng Xizi, Lan Yun, Tan Yizhou, Chen Weilie, Wang Yaping, Deng Xilong, Hu Fengyu, Li Feng
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
Guangzhou Laboratory, Bio-Island, Guangzhou, China.
Front Immunol. 2022 Mar 8;13:758946. doi: 10.3389/fimmu.2022.758946. eCollection 2022.
In contrast to dexamethasone, the clinical efficacy of methylprednisolone (MP) remains controversial, and a systems biology study on its mechanism is lacking. In this study, a total of 38 severe COVID-19 patients were included. The demographics, clinical characteristics, and severity biomarkers including C-reactive protein (CRP), d-dimer, albumin, and Krebs von den Lungen 6 of patients receiving MP (n=26, 40 mg or 80 mg daily for 3-5 days) and supportive therapy (n=12) were compared. Longitudinal measurements of 92 cytokines in MP group from admission to over six months after discharge were performed by multiplex Proximity Extension Assay. The results showed that demographics, baseline clinical characteristics were similar in MP and non-MP groups. No death occurred and the hospital stays between the two groups were similar. Kinetics studies showed that MP was not better than supportive therapy at improving the four severity biomarkers. Cytokines in MP group were characterized by five clusters according to their baseline levels and responses to MP. The immunological feature of severe COVID-19 could be defined by the "core signature" cytokines in cluster 2: MCP-3, IL-6, IFN-γ, and CXCL10, which strongly correlated with each other and CRP, and are involved in cytokine release storm. The "core signature" cytokines were significantly upregulated at baseline and remained markedly elevated after MP treatment. Our work showed a short course of MP therapy could not rapidly improve the immune disorders among severe COVID-19 patients or clinical outcomes, also confirmed "core signature" cytokines, as severity biomarkers similar to CRP, could be applied to evaluate clinical treatment effect.
与地塞米松不同，甲泼尼龙（MP）的临床疗效仍存在争议，且缺乏关于其作用机制的系统生物学研究。本研究共纳入38例重症新型冠状病毒肺炎（COVID-19）患者。比较了接受MP治疗（n = 26，每日40 mg或80 mg，持续3 - 5天）和支持治疗（n = 12）患者的人口统计学特征、临床特征以及包括C反应蛋白（CRP）、D-二聚体、白蛋白和肺表面活性物质相关蛋白A在内的严重程度生物标志物。采用多重邻近延伸分析对MP组患者从入院到出院后六个月以上的92种细胞因子进行纵向检测。结果显示，MP组和非MP组的人口统计学特征、基线临床特征相似。两组均未发生死亡，住院时间相似。动力学研究表明，在改善四项严重程度生物标志物方面，MP并不优于支持治疗。根据MP组细胞因子的基线水平和对MP的反应，可将其分为五个簇。重症COVID-19的免疫特征可由第2簇中的“核心特征”细胞因子定义：单核细胞趋化蛋白-3（MCP-3）、白细胞介素-6（IL-6）、干扰素-γ（IFN-γ）和CXC趋化因子配体10（CXCL10），它们彼此之间以及与CRP密切相关，并参与细胞因子释放风暴。“核心特征”细胞因子在基线时显著上调，MP治疗后仍明显升高。我们的研究表明，短期MP治疗不能迅速改善重症COVID-19患者的免疫紊乱或临床结局，同时也证实“核心特征”细胞因子作为与CRP类似的严重程度生物标志物，可用于评估临床治疗效果。
