Watkins Anne E, Fenichel Eli P, Weinberger Daniel M, Vogels Chantal B F, Brackney Doug E, Casanovas-Massana Arnau, Campbell Melissa, Fournier John, Bermejo Santos, Datta Rupak, Dela Cruz Charles S, Farhadian Shelli F, Iwasaki Akiko, Ko Albert I, Grubaugh Nathan D, Wyllie Anne L
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA.
Yale School of the Environment, Yale University, New Haven, CT 06510, USA.
medRxiv. 2020 Sep 3:2020.09.02.20183830. doi: 10.1101/2020.09.02.20183830.
Expanding testing capabilities is integral to managing the further spread of SARS-CoV-2 and developing reopening strategies, particularly in regards to identifying and isolating asymptomatic and pre-symptomatic individuals. Central to meeting testing demands are specimens that can be easily and reliably collected and laboratory capacity to rapidly ramp up to scale. We and others have demonstrated that high and consistent levels of SARS-CoV-2 RNA can be detected in saliva from COVID-19 inpatients, outpatients, and asymptomatic individuals. As saliva collection is non-invasive, extending this strategy to test pooled saliva samples from multiple individuals could thus provide a simple method to expand testing capacity. However, hesitation towards pooled sample testing arises due to the dilution of positive samples, potentially shifting weakly positive samples below the detection limit for SARS-CoV-2 and thereby decreasing the sensitivity. Here, we investigated the potential of pooling saliva samples by 5, 10, and 20 samples prior to RNA extraction and RT-qPCR detection of SARS-CoV-2. Based on samples tested, we conservatively estimated a reduction of 7.41%, 11.11%, and 14.81% sensitivity, for each of the pool sizes, respectively. Using these estimates we modeled anticipated changes in RT-qPCR cycle threshold to show the practical impact of pooling on results of SARS-CoV-2 testing. In tested populations with greater than 3% prevalence, testing samples in pools of 5 requires the least overall number of tests. Below 1% however, pools of 10 or 20 are more beneficial and likely more supportive of ongoing surveillance strategies.
扩大检测能力对于控制新冠病毒的进一步传播和制定重新开放策略至关重要,特别是在识别和隔离无症状及症状前感染者方面。满足检测需求的核心是能够轻松、可靠地采集的样本以及能够迅速扩大规模的实验室能力。我们和其他研究表明,在新冠肺炎住院患者、门诊患者及无症状感染者的唾液中能够检测到高水平且稳定的新冠病毒RNA。由于唾液采集是非侵入性的,因此将此策略扩展到检测多个个体的混合唾液样本可以提供一种扩大检测能力的简单方法。然而,由于阳性样本的稀释,可能会使弱阳性样本低于新冠病毒的检测限,从而降低敏感性,人们对混合样本检测存在疑虑。在此,我们研究了在提取RNA和进行新冠病毒RT-qPCR检测之前,将唾液样本按5份、10份和20份进行混合的潜力。基于所检测的样本,我们保守估计,对于每种混合样本量,敏感性分别降低7.41%、11.11%和14.81%。利用这些估计值,我们对RT-qPCR循环阈值的预期变化进行了建模,以显示混合样本对新冠病毒检测结果的实际影响。在患病率高于3%的受测人群中,将样本按5份一组进行检测所需的总体检测次数最少。然而,在患病率低于1%时,10份或20份一组的混合样本更有益,可能也更有助于持续的监测策略。