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--严重急性呼吸道--引起的严重肺炎的爆发 综合症冠状病毒(SARS-CoV-2)，于2019年12月在武汉出现，中国。没有足够的机会获得 检测限制了我们对这种新流行病在美国的程度的了解。 快速检测策略是填补这一空白的当务之急。 这是UCSD HIV临床试验协作中心(CTU)的行政补充，用于筛查所有患者- 面对研究人员和部分研究参与者直接响应PA-18-591和NOSI AI- 20-031，因为它可以安全地恢复我们三个美国临床研究站点(CRSS)的关键研究服务 (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)，服务于可能有较高风险的艾滋病毒(PWH)携带者 新冠肺炎。研究与护理相协调的连续性对于结束艾滋病毒流行的进展至关重要 而不会让员工和参与者在研究环境中面临收购新冠肺炎的风险。没有其他本地人 政府或卫生系统正在采用这种方法。 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的流行情况： 与威尔斯亲王医院有直接接触的无症状研究人员和研究参与者中的CoV-2 对于研究访问，确定新的事件感染，并可能防止无症状的携带者传播 SARS-CoV-2至威尔斯亲王医院。这项提议在概念上是创新的，因为它应用了核酸测试(NAT)池 节省测试用品、个人防护设备和资金以解决紧迫需求的技术 进行更多的测试。由于没有技术障碍，测试可以立即开始。 我们将筛选(1)直接护理研究人员，在加州大学圣地亚哥分校(n=40)每周3天，在南加州大学(n=8)每周筛查一次。 用于无症状SARS-CoV-2的UCH(n=20)和(2)每个地点10名研究参与者的子集 考试日。自行收集的鼻拭子样本将使用NAT池平台(UCSD AVRC CRS)进行测试 或基于个体RT-PCR的商业SARS-CoV-2检测(USC和UCH CRSS)。 我们的理由是，通过利用我们在池NAT方面的CTU专业知识，三家公司的基础设施容量 CRSS和圣地亚哥艾滋病研究中心(CFAR)，我们将实施和评估具有成本效益的 确定SARS-CoV-2感染流行和免疫应答的筛查方法 直接护理研究人员和回归研究参与者之间的(即血清阳性率)(目标1)和 确定联合检测(UCSD AVRC)与基于单个RT-PCR的检测特性 商业SARS-CoV-2检测(USC和UCH CRSS，AIM 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危环境中，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.