新型冠状病毒肺炎病情严重程度与预后指标相关性的Meta分析

Prognostic Indicators for Severity in COVID-19 Patients:a Meta-analysis

背景世界卫生组织表示新型冠状病毒肺炎(COVID-19)的爆发已经构成一次全球性的“大流行”,其病情严重程度影响患者预后。目的探索COVID-19病情严重程度和预后指标的相关性,从而确定预后指标对病情严重程度的评估和预测价值,为临床COVID-19的病情转归及预后评估提供参考。方法计算机检索The Cochrane Library、EMBase、PubMed、Web of Science、SinoMed、中国知网、万方数据知识服务平台、维普网,收集分为重症组和非重症组或死亡组和存活组的COVID-19随机对照试验,并且包含降钙素原(PCT)、C反应蛋白(CRP)、淋巴细胞计数(LYM)、白介素-6(IL-6)、D-二聚体(D-dimer)预后相关指标,文献检索时间是建库至2020-09-03。采用改良Jaded评分量表对文献进行质量评价,运用Stata 12.0软件进行Meta分析。结果共纳入15篇文献,1476例患者,Jadad评分均在4~5分,均为高质量文献。Meta分析结果显示,重症组患者的PCT〔SMD=-2.28,95%CI(-3.60,-0.98),P<0.001〕、CRP〔SMD=-2.23,95%CI(-3.38,-1.07),P<0.001〕、IL-6〔SMD=-2.97,95%CI(-4.94,-1.00),P<0.001〕、D-dimer〔SMD=-1.22,95%CI(-2.66,0.21),P=0.008〕高于非重症组。死亡组患者的PCT〔SMD=-4.11,95%CI(-9.98,1.76),P=0.007〕、CRP〔SMD=-2.73,95%CI(-4.21,-1.25),P<0.001〕、IL-6〔SMD=-3.79,95%CI(-4.90,-2.67),P<0.001〕、D-dimer〔SMD=-0.68,95%CI(-1.46,0.09),P=0.009〕高于存活组。重症组患者的LYM低于非重症组〔SMD=1.41,95%CI(0.34,2.48),P<0.001〕,死亡组患者的LYM低于存活组〔SMD=2.08,95%CI(0.93,3.22),P<0.001〕。结论重型COVID-19患者的PCT、CRP、IL-6、D-dimer高于非重型COVID-19患者,LYM低于非重型COVID-19患者;死亡组COVID-19患者的PCT、CRP、IL-6、D-dimer高于存活组,LYM低于存活组,提示PCT、CRP、IL-6、D-dimer可能与病情严重程度呈正相关,LYM可能与病情严重程度呈负相关。PCT、CRP、IL-6、D-dimer过高以及LYM过低将不利于病情转归,可作为预后指标对患者预后情况进行预测。

Background The COVID-19 has become a global pandemic declared by the WHO,and the severity of which affects the prognosis of patients.Objective To explore the prognostic indicators for severity and their predictive values in COVID-19 patients,providing a reference for clinical prediction of patients'outcome and prognosis.Methods Eight databases(the Cochrane Library,Embase,PubMed,Web of Science,SinoMed,CNKI,Wanfang Data Knowledge Service Platform,VIP)were searched from inception to 2020-09-03 for randomized controlled trials(RCTs)about severe versus non-severe COVID-19 patients or deceased versus survived COVID-19 patients with prognostic indicators〔including procalcitonin(PCT)〕,C-reactive protein(CRP),lymphocyte count(LYM),interleukin-6(IL-6),(D-dimer)studied.The modified Jaded Scale was used to assess the methodological quality.Stata 12.0 was used for meta-analysis.Results Fifteen RCTs were included,involving 1476 cases,all were assessed with high methodological quality(modified Jadad Scale score ranging from 4 to 5 points).Meta-analysis found that severe COVID-19 patients had higher mean values of PCT〔SMD=-2.28,95%CI(-3.60,-0.98),P<0.001〕,CRP〔SMD=-2.23,95%CI(-3.38,-1.07),P<0.001〕,IL-6〔SMD=-2.97,95%CI(-4.94,-1.00),P<0.001〕,and D-dimer〔SMD=-1.22,95%CI(-2.66,0.21),P=0.008〕than non-severe COVID-19 patients.Severe COVID-19 patients had lower mean LYM〔SMD=1.41,95%CI(0.34,2.48),P<0.001〕.The deceased COVID-19 patients had higher mean values of PCT〔SMD=-4.11,95%CI(-9.98,1.76),P=0.007〕,CRP〔SMD=-2.73,95%CI(-4.21,-1.25),P<0.001〕,IL-6〔SMD=-3.79,95%CI(-4.90,-2.67),P<0.001〕,and D-dimer〔SMD=-0.68,95%CI(-1.46,0.09),P=0.009〕than the survived.The deceased COVID-19 patients had lower mean LYM〔SMD=2.08,95%CI(0.93,3.22),P<0.001〕.Conclusion Increased PCT,CRP,IL-6 and D-dimer and decreased LYM were found in severe or deceased COVID-19 patients,indicating that the former three may be positively correlated with severity,while the latter may be negatively correlated with severity.These five indicators may be used as prognostic indicators for severity,too high PCT,CRP,IL-6 and D-dimer,and too low LYM may suggest a poor prognosis.