背景:2019年冠状病毒病(COVID-19)的管理和控制依赖于可靠的诊断测试。
目的:评估核酸扩增试验(NAAT)诊断冠状病毒感染的诊断试验准确性(DTA)。
方法:PubMed,WebofScience,Cochrane图书馆,Embase,打开灰色和会议进行到2019年5月。PubMed和medRxiv于2020年8月31日更新了COVID-19。
方法:如果研究报告了使用临床样本的不同NAAT之间的一致率,则研究合格。
方法:疑似上呼吸道或下呼吸道冠状病毒感染的症状患者。
方法:将新的NAAT定义为指数测试,将现有的NAAT定义为参考标准。数据以一式两份独立提取。使用诊断准确性研究质量评估2工具评估偏倚风险。报告了通过双变量荟萃分析汇总的总体敏感性/特异性周围的置信区(CR)。使用meta回归评估异质性。
结果:纳入了51项研究,其中22人包括COVID-19之前的10.181人和29人,其中包括8742人被诊断患有严重急性呼吸道综合症冠状病毒2(SARS-CoV-2)。总体汇总敏感性为89.1%(95%CR84.0-92.7%),特异性为98.9%(95%CR98.0-99.4%)。几乎所有的研究都评估了不同的PCRs作为指标和参考标准。实时RTPCR检测的灵敏度明显高于其他检测方法。高偏倚风险的参考标准可能夸大了特异性。评估SARS-COV-2的研究的合并敏感性和特异性分别为90.4%(95%CR83.7-94.5%)和98.1%(95%CR95.9-99.2),分别。使用下呼吸道样本的SARS-COV-2研究,实时RT-PCR,针对N或S基因或多个基因的测试显示出更高的敏感性,和基于逆转录酶环介导等温扩增(RT-LAMP)的测定,特别是当只靶向RNA依赖性RNA聚合酶(RdRp)基因时,与其他研究相比,灵敏度明显较低。
结论:汇集迄今为止的所有研究表明,平均10%的冠状病毒感染患者可能被PCR检测漏诊。影响灵敏度和特异性的变量可用于测试选择和开发。
BACKGROUND: Management and control of coronavirus disease 2019 (COVID-19) relies on reliable diagnostic testing.
OBJECTIVE: To evaluate the diagnostic test accuracy (DTA) of nucleic acid amplification tests (NAATs) for the diagnosis of coronavirus infections.
METHODS: PubMed, Web of Science, the Cochrane Library, Embase, Open Grey and conference proceeding until May 2019. PubMed and medRxiv were updated for COVID-19 on 31st August 2020.
METHODS: Studies were eligible if they reported on agreement rates between different NAATs using clinical samples.
METHODS: Symptomatic patients with suspected upper or lower respiratory tract coronavirus infection.
METHODS: The new NAAT was defined as the index test and the existing NAAT as reference standard. Data were extracted independently in duplicate. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Confidence regions (CRs) surrounding summary sensitivity/specificity pooled by bivariate meta-analysis are reported. Heterogeneity was assessed using meta-regression.
RESULTS: Fifty-one studies were included, 22 of which included 10 181 persons before COVID-19 and 29 including 8742 persons diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The overall summary sensitivity was 89.1% (95%CR 84.0-92.7%) and specificity 98.9% (95%CR 98.0-99.4%). Nearly all the studies evaluated different PCRs as both index and reference standards. Real-time RT PCR assays resulted in significantly higher sensitivity than other tests. Reference standards at high risk of bias possibly exaggerated specificity. The pooled sensitivity and specificity of studies evaluating SARS-COV-2 were 90.4% (95%CR 83.7-94.5%) and 98.1% (95%CR 95.9-99.2), respectively. SARS-COV-2 studies using samples from the lower respiratory tract, real-time RT-PCR, and tests targeting the N or S gene or more than one gene showed higher sensitivity, and assays based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP), especially when targeting only the RNA-dependent RNA polymerase (RdRp) gene, showed significantly lower sensitivity compared to other studies.
CONCLUSIONS: Pooling all studies to date shows that on average 10% of patients with coronavirus infections might be missed with PCR tests. Variables affecting sensitivity and specificity can be used for test selection and development.