Pooled and conventional nucleic acid testing strategies for SARS-CoV-2 to screen direct care research staff and protect HIV patients

摘要 由一种以前未知的病毒病原体引起的严重肺炎爆发，严重急性呼吸道感染， 综合征冠状病毒（SARS-CoV-2），于2019年12月在中国武汉出现。不能充分获得 测试限制了我们对这种新流行病在美国的程度的理解。 快速检测策略急需填补这一空白。 UCSD协作HIV临床试验单位（CTU）的这一行政补充，以筛选所有患者- 面对研究人员和研究参与者的比例是直接响应PA-18-591和NOSI AI- 20-031，因为它可以允许我们的三个美国临床研究中心（CRS）安全恢复关键研究服务 (UCSD抗病毒研究中心[AVRC] CRS、南加州大学[USC] CRS和 科罗拉多大学医院[UCH] CRS），为艾滋病毒感染者（PWH）提供服务，这些人可能有更高的感染风险， 2019冠状病毒病。研究的连续性与护理的协调对于结束艾滋病毒流行至关重要 而不会使员工和参与者在研究环境中面临感染COVID-19的风险。没有其他本地 政府或卫生系统正在采取这种办法。 我们的目标是实施和评估一种具有成本效益的筛查方法，以确定SARS的流行程度- 与威尔斯亲王医院直接接触的无症状研究人员和正在就诊的研究参与者中的CoV-2 对于研究访视，确定新的事件感染，并可能预防无症状携带者传播 SARS冠状病毒2型呼叫威尔斯亲王医院该提议在概念上是创新的，因为其应用核酸测试（NAT）合并 节省测试用品、个人防护设备和资金的技术，以满足迫切需要 增加测试。由于没有技术障碍，测试可以立即开始。 我们将筛选（1）UCSD（n=40）和USC（n=8）每周3天/周的直接护理研究人员， 无症状SARS-CoV-2的UCH（n=20）和（2）每个研究中心10名研究参与者的子集， 测试日将使用NAT合并平台（UCSD AVRC CRS）检测自我采集的鼻拭子样本 或基于RT-PCR的商业SARS-CoV-2检测（USC和UCH CRS）。 我们的理由是，通过利用CTU在池化NAT方面的专业知识， CRS和圣地亚哥艾滋病研究中心（CFAR），我们将实施和评估一项具有成本效益的 确定SARS-CoV-2感染流行率和SARS-CoV-2免疫应答的筛查方法 (i.e.直接护理研究人员和返回的研究参与者（目标1）中的血清阳性率）， 确定合并检测（UCSD AVRC）与基于单个RT-PCR的检测特征 商业SARS-CoV-2测试（USC和UCH CRS，目标2）。一旦得到验证，就可以部署此方法 在其他环境中，以帮助确保安全返回工作程序或在高风险环境中，如医护人员 在癌症或艾滋病诊所或疗养院。

ABSTRACT An outbreak of serious pneumonia caused by a previously unknown viral pathogen, severe acute respiratory syndrome coronavirus (SARS-CoV-2), emerged in Wuhan, China in December 2019. Inadequate access to testing has limited our understanding of the extent of this new epidemic in the U.S. A cost effective accurate and rapid testing strategy is urgent to fill this gap. This administrative supplement to the UCSD Collaborative HIV Clinical Trials Unit (CTU) to screen all patient- facing research staff and a proportion of research participants is directly responsive to PA-18-591 and NOSI AI- 20-031 as it may allow safe resumption of key research services at our three U.S. Clinical Research Sites (CRSs) (UCSD Antiviral Research Center [AVRC] CRS, the University of Southern California [USC] CRS and the University of Colorado Hospital [UCH] CRS), serving persons with HIV (PWH) who may be at higher risk for COVID-19. Continuity of research coordinated with care is critical in progress toward ending the HIV epidemic without putting staff and participants at risk for COVID-19 acquisition in the research setting. No other local government or health systems are undertaking this approach. Our goal is to implement and evaluate a cost-effective screening approach to determine the prevalence of SARS- CoV-2 in asymptomatic research staff who are in direct contact with PWH and research participants being seen for study visits, identify new incident infections and potentially prevent asymptomatic carrier transmission of SARS-CoV-2 to PWH. This proposal is conceptually innovative in that it applies nucleic acid test (NAT) pooling techniques to save testing supplies, personal protective equipment and money to address an immediate need for increased testing. As there are no technical barriers, testing can start immediately. We will screen (1) direct care research personnel 3 days/week at UCSD (n=40) and weekly at USC (n=8) and UCH (n=20) for asymptomatic SARS-CoV-2 and (2) a subset of 10 research participants at each site every testing day. Self-collected nasal swab samples will be tested using a NAT pooling platform (UCSD AVRC CRS) or individual RT-PCR based commercial SARS-CoV-2 testing (USC and UCH CRSs). Our rationale is that by leveraging our CTU expertise in pooled NAT, the infrastructure capacity of the three CRSs and the San Diego Center for AIDS Research (CFAR), we will implement and evaluate a cost-effective screening approach to determine the prevalence of SARS-CoV-2 infection and SARS-CoV-2 immune response (i.e. seroprevalence) among direct care research staff and returning research participants (Aim 1) and to determine the test characteristics of pooled testing (UCSD AVRC) compared to individual RT-PCR based commercial SARS-CoV-2 testing (USC and UCH CRSs, Aim 2). Once validated, this approach can be deployed in other settings to help ensure safe return to work procedures or in high-risk settings such as healthcare workers in cancer or HIV clinics or nursing homes.