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 (LOC) 实施急性 SARS-CoV-2 自然史试验 住院和非住院个体的感染：“急性免疫反应的前瞻性研究 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巨大差距 先天性和适应性免疫功能在改变 COVID-19 疾病和清除病毒方面的贡献 感染以及疫苗预防或改变 SARS-CoV-2 感染者的 COVID-19 疾病的能力 个人。为了解决这一差距，美国国立卫生研究院 (NIH) 领导了 CoVPN 的快速组建， 与 5 个 NIH 支持的临床试验网络合作，创建一个增强的医师科学家网络 64 美国（US）及15个国家55个国际临床试验中心致力于全球发展 针对 SARS-CoV-2 的有效疫苗。由于其实施全球艾滋病毒疫苗试验的丰富经验 在过去 20 年中，HIV 疫苗试验网络 (HVTN) LOC 被选为 CoVPN 的 LOC 疫苗试验。 我们相信 CoVPN 完全有能力研究自然历史差距并在全球范围内快速部署这些信息 SARS-CoV-2 中和疫苗和 mAb 疗法的开发。在这项研究中，我们建议发起一项 在美国 17 个国家招募约 800 名急性感染者的观察性队列研究 以及为期 8 个月的 43 个国际临床试验中心。 RT-PCR 呈阳性的 18 岁及以上成年人 SARS-CoV-2 检测结果将在各个试验地点竞争性入组，直至达到全部队列。 参与者将在 28 天内跟踪 6 次诊所就诊，并在一个月内收到最后一次远程联系 上次访问后。经历临床失代偿的参与者将被转介接受医院评估。 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 以及针对 SARS-CoV-2 的体液、先天和细胞免疫反应的质量、强度和动力学 无症状和急性症状参与者（住院和非住院）的感染 来自不同地理和遗传背景的个体）。 这项自然历史研究将告诉我们很多关于急性感染者的适应性免疫反应的信息。 感染 SARS-CoV-2 并将揭示免疫系统在成功清除中所起的作用 的感染。它将提高我们对反应的动态和持续时间的理解，以及 表位特异性和其他定义特征，并将为预防和预防的合理设计和测试提供信息 治疗性疫苗和单克隆抗体。最后，这项研究将为大型网络做好准备 许多 COVID-19 疫苗现已进入临床试验渠道。

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.