Lessons from applied large-scale pooling of 133,816 SARS-CoV-2 RT-PCR tests.
Lessons from applied large-scale pooling of 133,816 SARS-CoV-2 RT-PCR tests.
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DOI：
10.1126/scitranslmed.abf2823
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发表时间：
2021-04-14
影响因子：
17.1
通讯作者：
Hebrew University-Hadassah COVID-19 Diagnosis Team
中科院分区：
文献类型：
--
作者：
Barak N;Ben-Ami R;Sido T;Perri A;Shtoyer A;Rivkin M;Licht T;Peretz A;Magenheim J;Fogel I;Livneh A;Daitch Y;Oiknine-Djian E;Benedek G;Dor Y;Wolf DG;Yassour M;Hebrew University-Hadassah COVID-19 Diagnosis Team
基于阳性率的SARS-CoV-2检测的自适应样本池在不影响特异性或敏感性的情况下避免了76%的测试反应。基于RT-PCR的频繁和准确的检测对于预防和管理SARS-CoV-2感染是必不可少的；然而，主动的感染监测往往受到时间或资源的限制。Cleary等人。结果表明，考虑人群水平的病毒流行率和个体病毒载量可以在灵敏度损失最小的情况下提高联合检测的效率，这在理论上和使用人类拭子和痰样本的体外验证中都是如此。Barak等人。结果显示，对133,816名医院采集的患者鼻咽样本进行的联合检测消除了四分之三的检测反应，灵敏度仅略有下降，证明了该方法在现场的有效性。这两项研究都表明，在检测之前考虑合并单个样本可以可靠地增加SARS-CoV-2检测的吞吐量。在RNA提取和实时逆转录聚合酶链式反应(RT-PCR)分析之前，将多个拭子样本合并在一起，已被提出作为一种策略，以降低成本并增加SARS-CoV-2检测的吞吐量。然而，关于对SARS-CoV-2进行实际大规模群体测试的报道一直很少。关键的公开问题涉及样品稀释导致的灵敏度降低、假阳性率、实际效率(通过合并节省的测试数量)以及总体感染率对分析性能的影响。在这里，我们报告了对2020年4月至9月期间收集的133,816个样本的分析，这些样本由Dorfman Pooling进行了SARS-CoV-2的存在测试。我们避免了76%的RNA提取和RT-PCR测试，尽管流行率经常变化(0.5%到6%)。我们观察到池的效率和灵敏度超过了理论预测，这是由于池中阳性样本的非随机分布造成的。总体而言，我们的发现支持使用汇集来进行高效的大规模SARS-CoV-2检测。
Adaptive sample pooling for SARS-CoV-2 testing based on positivity rates spares 76% of test reactions without compromising specificity or sensitivity. Frequent and accurate RT-PCR–based testing is essential for preventing and managing SARS-CoV-2 infection; however, active infection surveillance is still often limited by time or resources. Cleary et al. demonstrate that considering population-level viral prevalence and individual viral loads allows for efficiency gains upon pooled testing with minimal loss of sensitivity, both theoretically and as validated in vitro using human swab and sputum samples. Barak et al. show that pooled testing of 133,816 hospital-collected patient nasopharyngeal samples eliminated three quarters of testing reactions with only a minor reduction in sensitivity, demonstrating the efficacy of the approach in the field. Both studies suggest that considered pooling of individual samples before testing could reliably increase SARS-CoV-2 testing throughput. Pooling multiple swab samples before RNA extraction and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis has been proposed as a strategy to reduce costs and increase throughput of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests. However, reports on practical large-scale group testing for SARS-CoV-2 have been scant. Key open questions concern reduced sensitivity due to sample dilution, the rate of false positives, the actual efficiency (number of tests saved by pooling), and the impact of infection rate in the population on assay performance. Here, we report an analysis of 133,816 samples collected between April and September 2020 and tested by Dorfman pooling for the presence of SARS-CoV-2. We spared 76% of RNA extraction and RT-PCR tests, despite the frequently changing prevalence (0.5 to 6%). We observed pooling efficiency and sensitivity that exceeded theoretical predictions, which resulted from the nonrandom distribution of positive samples in pools. Overall, our findings support the use of pooling for efficient large-scale SARS-CoV-2 testing.
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作者：
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