CoVPN 5001 A prospective study of acute immune responses to SARS-CoV-2 infection SDMC

该提案概述了COVID-19预防网络（CoVPN）疫苗的科学议程 领导运营中心（Leadership Operations Center，简称CDC），用于实施急性SARS-CoV-2自然史试验 住院和非住院个体的感染：“急性免疫应答的前瞻性研究 SARS-CoV-2感染。 随着COVID-19大流行的爆发，我们认识到该领域的知识存在重大差距， 先天性和适应性免疫功能在改善COVID-19疾病和清除病毒中的作用 感染和疫苗预防或改变SARS-CoV-2感染者的COVID-19疾病的能力 个体为了解决这一差距，美国国家卫生研究院（NIH）领导了CoVPN的快速构建， 与5个NIH支持的临床试验网络合作，在64个国家建立一个增强的医生科学家网络， 美国（US）和15个国家的55个国际临床试验中心，致力于在全球范围内开发 SARS-CoV-2的有效疫苗由于其在实施全球艾滋病毒疫苗试验方面的丰富经验， 在过去的20年里，HIV疫苗试验网络（HVTN）被选为CoVPN的代理 疫苗试验 我们相信，CoVPN能够很好地研究自然历史的差距，并迅速将这些信息部署在 开发SARS-CoV-2中和疫苗和mAb疗法。在这项研究中，我们建议启动一个 在17个美国（US）招募的约800名急性感染者的观察性队列研究 和43个国际临床试验中心进行了为期8个月的研究。18岁及以上RT-PCR阳性的成人 SARS-CoV-2检测结果将在各试验中心竞争性入组，直至达到完整队列。 参与者将在28天内随访6次门诊访视，并在一个月内接受最后一次远程联系 在最后一次访问之后。发生临床失代偿的受试者将被转诊接受医院评估。 该研究的具体目标是生成表征SARS-CoV-2病毒动力学的标准化数据集 以及对SARS-CoV-2的体液、先天和细胞免疫应答的质量、幅度和动力学 无症状和急性症状受试者（住院和非住院受试者）中的感染 个体）来自不同的地理和遗传背景。 这项自然史研究将告诉我们很多关于急性免疫缺陷患者的适应性免疫反应的信息。 感染了SARS-CoV-2，并将阐明免疫系统在成功清除SARS-CoV-2中所起的作用。 感染它将提高我们对反应的动态和持续时间的理解， 表位特异性和其他定义签名，并将告知合理的设计和测试的预防和 治疗性疫苗和单克隆抗体。最后，这项研究将为大型 目前正在进入临床试验管道的COVID-19疫苗数量。

This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of a natural history trial for acute SARS-CoV-2 infection in hospitalized and non-hospitalized individuals: “A Prospective Study of Acute Immune Responses to SARS-CoV-2 Infection.” With the onset of the COVID-19 pandemic, we recognize there is a significant gap in knowledge in the field on the contribution of innate and adaptive immune functions in modifying COVID-19 disease and in clearing viral infection and in the ability of vaccines to prevent or modify COVID-19 disease in SARS-CoV-2 infected individuals. Addressing this gap, the National Institute of Health (NIH) led rapid constitution of the CoVPN, partnering 5 NIH supported clinical trial networks, to create an enhanced network of physician scientists at 64 United States (US) and 55 international clinical trial sites in 15 countries dedicated to developing globally effective vaccines for SARS-CoV-2. Due to its extensive experience implementing global HIV vaccine trials over the last 20 years, the HIV Vaccine Trials Network (HVTN) LOC was selected as the LOC for CoVPN vaccine trials. We believe the CoVPN is well placed to study the natural history gaps and rapidly deploy this information in the development of SARS-CoV-2 neutralizing vaccines and mAb therapies. In this study we propose initiating an observational cohort study of approximately 800 acutely infected persons recruited at 17 United States (US) and 43 international clinical trial sites over an 8 month period. Adults 18 years and older with RT-PCR positive SARS-CoV-2 test results will be enrolled competitively across trial sites until the full cohort is reached. Participants will follow up for 6 clinic visits over a 28 day period and receive a final remote contact one month after the last visit. Participants who experience clinical decompensation will be referred for hospital evaluation. Specific aims of the study are to generate standardized datasets characterizing the SARS-CoV-2 viral kinetics and the quality, magnitude, and kinetics of humoral, innate and cellular immune responses to SARS-CoV-2 infection in asymptomatic and acutely symptomatic participants (in both hospitalized and non-hospitalized individuals) from a diversity of geographic and genetic backgrounds. This natural history study will tell us much about the adaptive immune responses in persons who are acutely infected from SARS-CoV-2 and will shed light on the role the immune system plays in successfully clearance of infection. It will improve our understanding of the dynamics and duration of responses, as well as the epitope specificity and other defining signatures, and will inform rational design and testing of preventive and therapeutic vaccines and monoclonal antibodies. Lastly, this study will prepare the network for the large number of COVID-19 vaccines now entering the clinical trial pipeline.