Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, China.
Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Immunol. 2023 Jan 31;14:1111920. doi: 10.3389/fimmu.2023.1111920. eCollection 2023.
Coronavirus disease 2019 (COVID-19) is increasing worldwide, with complications due to frequent viral mutations, an intricate pathophysiology, and variable host immune responses. Biomarkers with predictive and prognostic value are crucial but lacking.
Serum samples from authentic and D614G variant (non-Omicron), and Omicron-SARS-CoV-2 infected patients were collected for METRNβ detection and longitudinal cytokine/chemokine analysis. Correlation analyses were performed to compare the relationships between serum METRNβ levels and cytokines/chemokines, laboratory parameters, and disease severity. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were used to evaluate the predictive value of METRNβ in COVID-19.
The serum level of METRNβ was highly elevated in non-Omicron-SARS-CoV-2 infected patients compared to healthy individuals, and the non-survivor displayed higher METRNβ levels than survivors among the critical ones. METRNβ concentration showed positive correlation with viral load in NAPS. ROC curve showed that a baseline METRNβ level of 1886.89 pg/ml distinguished COVID-19 patients from non-infected individuals with an AUC of 0.830. Longitudinal analysis of cytokine/chemokine profiles revealed a positive correlation between METRNβ and pro-inflammatory cytokines such as IL6, and an inverse correlation with soluble CD40L (sCD40L). Higher METRNβ was associated with increased mortality. These findings were validated in a second and third cohort of COVID-19 patients identified in a subsequent wave.
Our study uncovered the precise role of METRNβ in predicting the severity of COVID-19, thus providing a scientific basis for further evaluation of the role of METRNβ in triage therapeutic strategies.
新型冠状病毒病 2019（COVID-19）在全球范围内不断增加，由于频繁的病毒突变、复杂的病理生理学和宿主免疫反应的变化，导致并发症不断增加。具有预测和预后价值的生物标志物至关重要，但目前仍缺乏此类标志物。
收集了来自真实患者和 D614G 变异株（非奥密克戎）以及奥密克戎-SARS-CoV-2 感染患者的血清样本，用于检测 METRNβ 和进行纵向细胞因子/趋化因子分析。进行相关性分析以比较血清 METRNβ 水平与细胞因子/趋化因子、实验室参数和疾病严重程度之间的关系。使用受试者工作特征（ROC）曲线和 Kaplan-Meier 生存曲线评估 METRNβ 在 COVID-19 中的预测价值。
与健康个体相比，非奥密克戎-SARS-CoV-2 感染患者的血清 METRNβ 水平显著升高，危重症患者中，非幸存者的 METRNβ 水平高于幸存者。NAPs 中的 METRNβ 浓度与病毒载量呈正相关。ROC 曲线显示，基线 METRNβ 水平为 1886.89 pg/ml 时，区分 COVID-19 患者和未感染者的 AUC 为 0.830。细胞因子/趋化因子谱的纵向分析显示，METRNβ 与促炎细胞因子（如 IL6）呈正相关，与可溶性 CD40L（sCD40L）呈负相关。较高的 METRNβ 与死亡率增加相关。这些发现在随后的 COVID-19 患者的第二和第三批队列中得到了验证。
我们的研究揭示了 METRNβ 在预测 COVID-19 严重程度方面的精确作用，从而为进一步评估 METRNβ 在分诊治疗策略中的作用提供了科学依据。
