多效性白细胞介素-6（IL-6）和白细胞介素-10（IL-10）水平升高与COVID-19的严重程度和死亡率密切相关：对147项研究的最新纵向荟萃分析和系统评价
Elevated Levels of Pleiotropic Interleukin-6 (IL-6) and Interleukin-10 (IL-10) are Critically Involved With the Severity and Mortality of COVID-19: An Updated Longitudinal Meta-Analysis and Systematic Review on 147 Studies.
作者信息
Jafrin Sarah, Aziz Md Abdul, Islam Mohammad Safiqul
机构信息
Laboratory of Pharmacogenomics and Molecular Biology, Department of Pharmacy, Faculty of Science, Noakhali Science and Technology University, Sonapur, Noakhali, Bangladesh.
Department of Pharmacy, Faculty of Pharmacy and Health Sciences, State University of Bangladesh, Dhaka, Bangladesh.
出版信息
Biomark Insights. 2022 Jun 16;17:11772719221106600. doi: 10.1177/11772719221106600. eCollection 2022.
OBJECTIVES
Disruption in the natural immune reaction due to SARS-CoV-2 infection can initiate a potent cytokine storm among COVID-19 patients. An elevated level of IL-6 and IL-10 during a hyperinflammatory state plays a vital role in increasing the risk of severity and mortality. In this study, we aimed to evaluate the potential of circulating IL-6 and IL-10 levels as biomarkers for detecting the severity and mortality of COVID-19.
METHODS
This study was conducted according to the Cochrane Handbook and PRISMA guidelines. Authorized databases were searched to extract suitable studies using specific search terms. RevMan 5.4 was applied for performing the meta-analysis. Mean differences in IL-6 and IL-10 levels were calculated among COVID-19 patients via a random-effects model. NOS scoring, publication bias and sensitivity analyses were checked to ensure study quality.
RESULTS
A total of 147 studies were selected, with 31 909 COVID-19 patients under investigation. In the severity analysis, the mean concentration of IL-6 was significantly higher in the severe COVID-19 cases than in the non-severe cases (MD: 19.98; < .001; 95% CI: 17.56, 22.40). Similar result was observed for IL-10 mean concentration in severe COVID-19 cases (MD: 1.35; < .001; 95% CI: 0.90, 1.80). In terms of mortality analysis, circulating IL-6 showed sharp elevation in the deceased patients (MD: 42.11; < .001; 95% CI: 36.86, 47.36). IL-10 mean concentration was higher in the dead patients than in the survived patients (MD: 4.79; < .001; 95% CI: 2.83, 6.75). Publication bias was not found except for comparing IL-6 levels with disease severity. Sensitivity analysis also reported no significant deviation from the pooled outcomes.
CONCLUSIONS
Elevated levels of circulating IL-6 and IL-10 signifies worsening of COVID-19. To monitor the progression of SARS-CoV-2 infection, IL-6 and IL-10 should be considered as potential biomarkers for severity and mortality detection in COVID-19.
SYSTEMATIC REVIEW REGISTRATION
INPLASY registration number: INPLASY202240046.
目的
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染导致的自然免疫反应中断可在新型冠状病毒肺炎（COVID-19）患者中引发强烈的细胞因子风暴。炎症反应亢进状态下白细胞介素6（IL-6）和白细胞介素10（IL-10）水平升高在增加重症和死亡风险方面起着至关重要的作用。在本研究中，我们旨在评估循环IL-6和IL-10水平作为检测COVID-19严重程度和死亡率生物标志物的潜力。
方法
本研究按照Cochrane手册和系统评价与Meta分析的首选报告项目（PRISMA）指南进行。通过特定检索词检索授权数据库以提取合适的研究。应用RevMan 5.4进行Meta分析。采用随机效应模型计算COVID-19患者中IL-6和IL-10水平的平均差异。进行纽卡斯尔-渥太华量表（NOS）评分、发表偏倚和敏感性分析以确保研究质量。
结果
共纳入147项研究，涉及31909例接受调查的COVID-19患者。在严重程度分析中，重症COVID-19病例中IL-6的平均浓度显著高于非重症病例（平均差：19.98；P＜0.001；95%置信区间：17.56，22.40）。重症COVID-19病例中IL-10的平均浓度也有类似结果（平均差：1.35；P＜0.001；95%置信区间：0.90，1.80）。在死亡率分析方面，死亡患者中循环IL-6显著升高（平均差：42.11；P＜0.001；95%置信区间：36.86，47.36）。死亡患者中IL-10的平均浓度高于存活患者（平均差：4.79；P＜0.001；95%置信区间：2.83，6.75）。除了比较IL-6水平与疾病严重程度外，未发现发表偏倚。敏感性分析也显示与汇总结果无显著偏差。
结论
循环IL-6和IL-10水平升高表明COVID-19病情恶化。为监测SARS-CoV-2感染的进展，IL-6和IL-10应被视为COVID-19严重程度和死亡率检测的潜在生物标志物。
系统评价注册
国际系统评价平台（INPLASY）注册号：INPLASY202240046。
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