血清sTWEAK与新冠肺炎患者严重程度及预后的关联：一项前瞻性队列研究

Association between Serum sTWEAK and Severity and Prognosis of Patients with COVID-19’s Disease: A Prospective Cohort Study

摘要: 背景：可溶性肿瘤坏死因子样弱凋亡诱导因子(sTWEAK)是一种具有生物活性的细胞因子，广泛存在于多种组织和细胞中，参与刺激细胞生长、诱导炎性细胞因子和刺激细胞凋亡，已有研究证明sTWEAK水平升高与肺动脉高压、哮喘和慢性阻塞性肺疾病等呼吸系统疾病的发病机制相关。然而，sTWEAK在新冠肺炎中的作用尚未阐明。本课题旨在探讨血清sTWEAK水平与新冠肺炎患者病情严重程度和预后的关系。方法：本研究是一项前瞻性队列研究，入组了343例符合标准的新冠肺炎患者，系统收集了人口统计学数据和临床特征。采用酶联免疫吸附试验测定血清sTWEAK浓度。结果：在这项队列研究中，我们观察到新冠肺炎患者血清sTWEAK浓度随疾病严重程度评分呈协同性升高。线性回归与逻辑回归模型均发现血清sTWEAK水平与新冠肺炎严重程度评分存在显著正相关关系。经混杂因素调整后，入院时血清sTWEAK水平升高被证实会显著增加机械通气及入住重症监护室风险。与传统肺炎严重程度评分系统相比，受试者工作特征曲线下面积显示，在COVID-19患者中，血清sTWEAK水平对预后恶化的预测能力与传统严重程度评分相当。结论：血清sTWEAK水平升高不仅与新冠肺炎严重程度呈正相关，还可预测新冠肺炎患者的不良临床结局。血清sTWEAK可作为评估新冠肺炎严重程度和预测不良预后的新型生物标志物，有望在临床应用中为新冠肺炎患者提供更精准有效的治疗策略。

Abstract: Background: Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) is a biologically active cytokine widely distributed in various tissues and cells. It participates in stimulating cell growth, inducing inflammatory cytokines, and stimulating apoptosis. Previous studies have demonstrated that elevated sTWEAK levels are associated with the pathogenesis of respiratory diseases such as pulmonary hypertension, asthma, and chronic obstructive pulmonary disease. However, the role of sTWEAK in COVID-19 remains unclear. This study aims to investigate the relationship between serum sTWEAK levels and the severity and prognosis of COVID-19 patients. Methods: This prospective cohort study enrolled 343 eligible COVID-19 patients, and demographic and clinical characteristics were systematically collected. Serum sTWEAK concentration was measured using an enzyme-linked immunosorbent assay (ELISA). Results: In this cohort study, we observed a synergistic increase in serum sTWEAK concentration with disease severity scores in COVID-19 patients. Both linear and logistic regression models revealed a significant positive correlation between serum sTWEAK levels and COVID-19 severity scores. After adjusting for confounding factors, elevated serum sTWEAK levels at admission significantly increased the risk of mechanical ventilation and admission to the intensive care unit. Compared with the traditional pneumonia severity scoring system, the area under the receiver operating characteristic (AUC) curve showed that serum sTWEAK levels had comparable predictive power for prognostic deterioration in COVID-19 patients. Conclusion: Elevated serum sTWEAK levels are not only positively correlated with COVID-19 severity but can also predict adverse clinical outcomes in COVID-19 patients. Serum sTWEAK can serve as a novel biomarker for assessing COVID-19 severity and predicting adverse prognosis, and is expected to provide more precise and effective treatment strategies for COVID-19 patients in clinical applications.