RFA-IP-22-004, Michigan-Ford Initiative to Measure Vaccine Effectiveness (MFIVE): Seasonal Influenza, COVID-19 and Respiratory Virus Vaccines

A部分：衡量疫苗有效性的里根-福特倡议：季节性流感， 2019冠状病毒病和呼吸道病毒疫苗对医疗护理急性 门诊环境中的呼吸道疾病（MAARI）一直是疫苗有效性（VE）的基石 在美国的监测超过十年。作为美国流感VE网络的一部分，密歇根州 呼吸道病毒研究和应对中心拥有专业知识和基础设施， 支持SARS-CoV-2和流感实时VE评估的先前测试阴性研究结果 疫苗。我们的主要目标是在我们先前努力的基础上评估疫苗的有效性 SARS-CoV-2和流感病毒在预防MAARI中的作用。我们将在整个过程中进行VE监视 密歇根州东南部通过招募在门诊诊所和检测中心就诊的患者 跨越两个医疗体系我们的招生地点分布在多个社区， 该区域的卫生保健服务，包括为受传染病严重影响的人口提供服务的诊所。本研究将 抗体、病毒全基因组序列和非流感、非 SARS-CoV-2呼吸道病毒（如RSV）。我们将利用这些评估来扩大测试阴性 方法，以提供更准确和强大的评估价值工程。我们的具体目标如下： 目的1.确定流感和COVID-19疫苗在儿童和成人中的疫苗有效性， 门诊设置。我们将通过积极招募MAARI患者，收集和测试 呼吸道标本的检验，以及健康数据和疫苗接种史的核实。 目标2.进行流感和SARS-CoV-2病毒基因组测序，以进行监测和支持 VE的变异和分支特异性估计。我们将利用我们现有的强大的测序管道， 从研究和临床收集的呼吸道标本中及时获得测序数据。 目标3.有效维持SARS-CoV-2监测和COVID-19疫苗有效性评估 在流感病毒未传播期间的门诊患者中。我们会完成的 通过对我们参与的两大医疗中心的电子病历的标准化查询， 定期与国家疫苗接种登记数据整合。我们的主要成果将是迅速确定 疫苗的有效性，通过定期交付给疾病预防控制中心，以支持疫苗的建议，为一般 人口，并为未来疫苗的选择和开发提供信息。

Component A: Michigan-Ford Initiative to Measure Vaccine Effectiveness (MFIVE): Seasonal Influenza, COVID-19, and Respiratory Virus Vaccines The use of active surveillance for medically-attended acute respiratory illness (MAARI) in outpatient settings has been the cornerstone of vaccine effectiveness (VE) monitoring in the U.S. for over a decade. As a part of the U.S. Flu VE Network for 10 years, the Michigan Center for Respiratory Virus Research and Response has the expertise and the infrastructure to build upon the findings of previous test-negative studies to support real-time VE assessments for SARS-CoV-2 and influenza vaccines. Our primary goal is to build upon our previous efforts to evaluate the effectiveness of vaccines against SARS-CoV-2 and influenza in prevention of MAARI. We will conduct VE surveillance throughout Southeastern Michigan through recruitment of patients presenting at ambulatory clinics and testing centers spanning two healthcare systems. Our enrollment sites are distributed throughout multiple communities in the region, including clinics serving populations disproportionately impacted by infectious diseases. This study will integrate analyses of antibodies, whole genome sequences of viruses, and detection of non-influenza, non- SARS-CoV-2 respiratory viruses (e.g. RSV). We will use these evaluations to expand upon the test-negative methodology to provide a more accurate and robust assessment of VE. Our specific objectives are as follows: Objective 1. Determine vaccine effectiveness of influenza and COVID-19 vaccines in children and adults from ambulatory settings. We will do this through active enrollment of individuals with MAARI, collection and testing of respiratory specimens, and verification of health data and vaccination history. Objective 2. Conduct viral genomic sequencing of influenza and SARS-CoV-2 for surveillance and to support variant and clade-specific estimates of VE. We will leverage our existing, robust sequencing pipeline to provide timely sequencing data from both research and clinically-collected respiratory specimens. Objective 3. Efficiently maintain SARS-CoV-2 surveillance and COVID-19 vaccine effectiveness evaluations among ambulatory patients during periods when influenza viruses are not circulating. We will accomplish this through standardized queries of the electronic medical records of our two participating major medical centers, with regular integration with state vaccination registry data. Our primary outcome will be rapid determinations of vaccine effectiveness, through regular deliveries to CDC to support vaccine recommendations for the general population and to inform selection and development of future vaccines.