Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China.
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry, Peking Union Medical College, Beijing, China.
J Allergy Clin Immunol. 2020 Jul;146(1):119-127.e4. doi: 10.1016/j.jaci.2020.04.027. Epub 2020 Apr 29.
The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression.
We sought to identify biomarkers for disease severity and progression of COVID-19.
Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe, and 14 moderate patients were measured and analyzed in combination with clinical data.
Levels of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IFN-γ-induced protein 10, monocyte chemotactic protein-3, hepatocyte growth factor, monokine-induced gamma IFN, and macrophage inflammatory protein 1 alpha, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IFN-γ-induced protein 10 and monocyte chemotactic protein-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99.
In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of severe acute respiratory syndrome coronavirus 2 infection, and provide potential therapeutic targets and strategies.
由严重急性呼吸综合征冠状病毒 2 引起的 2019 年冠状病毒病（COVID-19）的爆发于 2019 年 12 月首次在武汉报告，并持续对公共健康构成严重威胁，凸显出确定疾病严重程度和进展的生物标志物的迫切需要。
我们旨在确定 COVID-19 疾病严重程度和进展的生物标志物。
测量并分析了 50 例 COVID-19 病例（包括 11 例危重症、25 例重症和 14 例中度）的血浆样本中的 48 种细胞因子，并结合临床数据进行分析。
发现 COVID-19 病例中的 14 种细胞因子水平显著升高，并且在不同疾病严重程度的患者中表现出不同的表达谱。此外，在疾病进展过程中与疾病严重程度高度相关的 IFN-γ 诱导蛋白 10、单核细胞趋化蛋白 3、肝细胞生长因子、单克隆诱导γ IFN 和巨噬细胞炎症蛋白 1α 的表达水平在危重症患者中显著更高，其次是重症患者，然后是中度患者。对 16 例患者中的 5 种细胞因子进行连续检测表明，持续高水平与疾病恶化和死亡结局相关。此外，IFN-γ 诱导蛋白 10 和单核细胞趋化蛋白 3是 COVID-19 进展的优秀预测因子，这两种细胞因子的组合在受体操作特征曲线计算中具有最大的曲线下面积，值为 0.99。
在这项研究中，我们报告了与 COVID-19 疾病严重程度和进展高度相关的生物标志物。这些发现增加了我们对严重急性呼吸综合征冠状病毒 2 感染的免疫病理机制的理解，并为潜在的治疗靶点和策略提供了依据。
