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

该提案概述了新冠肺炎预防网络疫苗的科学议程 领导运营中心(LOC)实施急性SARS-CoV-2自然病史试验 住院和非住院患者的感染：一项关于急性免疫反应的前瞻性研究 SARS-CoV-2感染。 随着新冠肺炎大流行的爆发，我们认识到该领域在以下方面的知识存在重大差距 先天免疫和获得性免疫功能在新冠肺炎病治疗和病毒清除中的作用 在SARS-CoV-2感染中疫苗预防或改变新冠肺炎病的能力 个人。为了解决这一差距，国家卫生研究所(NIH)领导了CoVPN的快速建立， 与5个美国国立卫生研究院支持的临床试验网络合作，创建了的内科科学家增强网络 美国和15个国家的55个国际临床试验基地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)LOC被选为CoVPN的LOC 疫苗试验。 我们相信，CoVPN处于有利地位，可以研究自然历史差距，并在 SARS-CoV-2中和疫苗和单抗治疗的发展。在这项研究中，我们建议发起一个 对在美国17个国家招募的大约800名急性感染者的观察性队列研究 和43个国际临床试验点在8个月的时间里。RT-PCR阳性的18岁及以上成年人 SARS-CoV-2检测结果将在各试验点进行竞争性登记，直到达到全部队列。 参与者将在28天内跟踪6次诊所访问，并在一个月内接受最终远程联系 在最后一次拜访之后。经历临床失代偿的参与者将被转介到医院进行评估。 这项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、天然和细胞免疫反应的质量、大小和动力学 无症状和有急性症状的参与者(住院和非住院)的感染情况 个人)，来自不同的地理和遗传背景。 这项自然历史研究将告诉我们许多关于人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病毒中所起的作用 感染的可能性。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标记，并将为合理设计和测试预防性和 治疗性疫苗和单抗。最后，这项研究将为大型网络做好准备 一些新冠肺炎疫苗目前正在进入临床试验管道。

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.