The Limit of Detection Matters: The Case for Benchmarking Severe Acute Respiratory Syndrome Coronavirus 2 Testing.
The Limit of Detection Matters: The Case for Benchmarking Severe Acute Respiratory Syndrome Coronavirus 2 Testing.
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DOI：
10.1093/cid/ciaa1382
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发表时间：
2021-11-02
期刊：
影响因子：
--
通讯作者：
Kirby JE
中科院分区：
文献类型：
--
作者：
Arnaout R;Lee RA;Lee GR;Callahan C;Cheng A;Yen CF;Smith KP;Arora R;Kirby JE
解决冠状病毒病2019年(新冠肺炎)大流行需要进行诊断测试，以确定哪些人感染了严重急性呼吸综合征冠状病毒2(SARS-CoV-2)。目前的金标准是对鼻咽样本进行逆转录-聚合酶链式反应(PCR)。一流的检测表明，每毫升运输介质中病毒RNA的检测极限(LOD)约为100份。然而，目前批准的检测方法的LOD差异超过10,000倍。LODS较高的检测将遗漏感染患者。然而，这些检测方法的相对临床敏感性仍不清楚。在这里，我们根据它们的LOD来模拟检测的临床敏感性。采用雅培实时SARS-CoV-2紧急使用授权试验从4700名首次阳性患者中获得周期阈值(Ct值)。根据聚合酶链式反应原理和经验分析，我们从CT推导出病毒载量。根据病毒载量分布相对于检测LOD的分析，发展了一种预测临床敏感性的滑动标度关系。CT值在短时间测试窗口内可靠地重复，为用作估计病毒载量的工具提供了支持。病毒载量被发现相对均匀地分布在log10个递增病毒载量箱中。根据这些数据，LOD每增加10倍，预计检测灵敏度将降低约13%。该检测方法对SARS-CoV-2检测的临床表现有重要影响。市场上最高的LODS将错过大多数感染患者。因此，化验应以通用标准为基准，以允许对SARS-CoV-2检测方法进行交叉比较。严重急性呼吸综合征冠状病毒2的逆转录聚合酶链式反应分析提供了定量数据。患者结果相对均匀地分布在Log10病毒载荷箱中。检测下限每增加10倍，灵敏度就会下降约13%。
Resolving the coronavirus disease 2019 (COVID-19) pandemic requires diagnostic testing to determine which individuals are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current gold standard is to perform reverse-transcription polymerase chain reaction (PCR) on nasopharyngeal samples. Best-in-class assays demonstrate a limit of detection (LoD) of approximately 100 copies of viral RNA per milliliter of transport media. However, LoDs of currently approved assays vary over 10,000-fold. Assays with higher LoDs will miss infected patients. However, the relative clinical sensitivity of these assays remains unknown. Here we model the clinical sensitivities of assays based on their LoD. Cycle threshold (Ct) values were obtained from 4700 first-time positive patients using the Abbott RealTime SARS-CoV-2 Emergency Use Authorization test. We derived viral loads from Ct based on PCR principles and empiric analysis. A sliding scale relationship for predicting clinical sensitivity was developed from analysis of viral load distribution relative to assay LoD. Ct values were reliably repeatable over short time testing windows, providing support for use as a tool to estimate viral load. Viral load was found to be relatively evenly distributed across log10 bins of incremental viral load. Based on these data, each 10-fold increase in LoD is expected to lower assay sensitivity by approximately 13%. The assay LoD meaningfully impacts clinical performance of SARS-CoV-2 tests. The highest LoDs on the market will miss a majority of infected patients. Assays should therefore be benchmarked against a universal standard to allow cross-comparison of SARS-CoV-2 detection methods. Reverse-transcription polymerase chain reaction assays for severe acute respiratory syndrome coronavirus 2 provide quantitative data. Patient results are relatively evenly distributed across log10 viral load bins. Each 10-fold increase in limit of detection corresponds to an approximate 13% loss in sensitivity.
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