Household Respiratory Virus SARS-CoV-2 Transmission and Immunity Sub-Study (HRTS)

由新型人类冠状病毒SARS-CoV-2造成的大流行已经产生了许多 关于COVID患者预防和治疗的最佳做法的未回答问题- 19种疾病。儿童缺乏明显的疾病易感性背后的机制也是 悬而未决。为了回答这些最关键的问题，我们需要关于宿主如何免疫的数据 系统对SARS-CoV-2感染和新冠肺炎疾病做出反应。纵向队列 在幼稚的种群中建立是仔细分析免疫反应所必需的， 疾病的严重性和保护性记忆的产生。疾病表现和结果 在不同年龄段和有各种潜在疾病的人群中差异很大， 使研究设计复杂化。大规模、特征良好的人类队列的启动和部署成本高昂 难以快速发展。在这项研究中，我们建议使用Divinci Consortium队列， 三个地理上截然不同的人类出生队列，它们已经建立并 成功运行，能够立即开始对疑似或 确诊为SARS-CoV-2感染。重要的是，这三个群体都有能力收集 家庭样本，提供对广泛的免疫和疾病进展的洞察 年龄范围。我们建议收集呼吸道样本、母乳、粪便/直肠拭子，以及 血清/PBMC样本，并从这些样本中详尽地分析宿主免疫反应 SARS-CoV-2。基于研究设计，我们将能够将原始时间点与 活动性感染期间的样本以及仍无症状的个体的样本 与那些出现不同程度症状的人相比。我们的研究建议 综合测量幼稚儿童外周血中免疫细胞群(基线) 样本和恢复期样本(感染后)。我们建议开发新的试剂来治疗 检测SARS-CoV-2特异性T、B细胞。此外，我们建议测量SARS-CoV-2 病毒多样性和进化。最后，我们将能够广泛地检测血清样本以 确定轻度和重度患者之间反应的可测量差异 感染以及无症状和有症状的感染，并跟踪他们随后的易感性 为了再次感染。Divinci财团的独特之处在于能够立即对 SARS-CoV-2大流行，最终目标是更全面地了解病毒 和疾病。

The pandemic created by the novel human coronavirus SARS-CoV-2 has generated many unanswered questions on the best practices for prevention and treatment for those with COVID- 19 disease. The mechanism behind the lack of apparent disease susceptibility in children is also unresolved. To answer these most critical questions, we require data on how the host immune system responds to SARS-CoV-2 infection and COVID-19 disease. Longitudinal cohorts established in naive populations are necessary for careful profiling of immune responses, disease severity, and the generation of protective memory. Disease presentation and outcome has been highly variable among age groups and those with various underlying conditions, complicating study design. Large well-characterized human cohorts are costly to initiate and difficult to develop quickly. In this study, we propose to use the DIVINCI Consortium cohorts, three geographically distinct human birth cohorts, which are already established and successfully running to be able to immediately begin sampling individuals with suspected or confirmed SARS-CoV-2 infection. Importantly, all three cohorts have the ability to collect household samples, providing insights into immunity and disease progression across a broad age range. We propose to collect respiratory samples, breast milk, stool/rectal swab, and serum/PBMC samples, and from those samples, exhaustively assay the host immune response to SARS-CoV-2. Based on the study design, we will be able to compare naive time points to those during active infection as well as samples from individuals who remained asymptomatic compared to those who develop varying degrees of symptoms. Our study proposes to comprehensively measure immune cell populations in the peripheral blood in naive (baseline) samples and convalescent samples (after infection.) We propose to develop novel reagents for measuring SARS-CoV-2-specific T and B cells. Further, we propose to measure SARS-CoV-2 viral diversity and evolution. Finally, we will be able to extensively assay serological samples to determine measurable differences in the response between individuals with mild and severe infection and asymptomatic and symptomatic infection, and track their subsequent susceptibility to re-infection. The DIVINCI consortium is uniquely situated to have immediate response to the SARS-CoV-2 pandemic with the ultimate goal of a more complete understanding of the virus and the disease.