VAccine failure: natural history and determinants of post-vaccination Covid-19

疫苗失败：Covid-19 疫苗接种后的自然史和决定因素

• 批准号: 10595580
• 负责人: John Daniel Kelly
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10595580
• 关键词: 2019-nCoV; Acute; Age; Body mass index; COVID-19; COVID-19 diagnosis; COVID-19 vaccination; COVID-19 vaccine; Case/Control Studies; Catchment Area; Cirrhosis; Clinical; Collaborations; Data; Diabetes Mellitus; Disease; Dose; Environmental Risk Factor; Epidemiology; Future; Goals; Healthcare; Hospitalization; Immune response; Immune system; Immunocompromised Host; Immunologics; Incidence; Individual; Integration Host Factors; Israel; Laboratories; Longitudinal cohort; Manufacturer; Medicare; Messenger RNA; Mutation; Natural History; Outcome; Pattern; Persons; Population; Populations at Risk; Positioning Attribute; Prevalence; Protocols documentation; Public Health; RNA vaccine; Reporting; Risk; Risk Factors; SARS-CoV-2 genome; SARS-CoV-2 infection; SARS-CoV-2 infection history; SARS-CoV-2 variant; Sampling; Subgroup; Symptoms; System; Thinking; Time; Vaccinated; Vaccination; Vaccinee; Vaccines; Variant; Veterans; Viral; Viral Genome; Viral Vector; booster vaccine; clinical care; cohort; comparative; data sharing networks; data warehouse; density; design; effectiveness study; efficacy trial; epidemiology study; experience; follow-up; high risk; hospitalization rates; human old age (65+); military veteran; mortality; novel vaccines; observational cohort study; population based; pragmatic study; primary care visit; programs; protective factors; response; unvaccinated; vaccination outcome; vaccination protocol; vaccine delivery; vaccine effectiveness; vaccine efficacy; vaccine failure; vaccine trial; variant of interest; variants of concern; whole genome

As SARS-CoV-2 vaccines enter mass distribution, little is known about vaccinated individuals who nonetheless develop Covid-19 (symptomatic disease or “vaccine failure”), require hospitalization, and die. Pfizer-BioNTech reported 3.8 vaccine failure cases/1,000 person-years, meaning vaccine failure will be relatively common on a population level. Pfizer, Moderna, and Janssen vaccine efficacy trials involved 35,000 to 50,000 individuals from which there are insufficient numbers to study vaccine failure, calling for post-vaccination surveillance with observational cohort studies in real-world settings. Using the VHA Corporate Data Warehouse (CDW) and the Covid-19 Shared Data Resource, we can harness real-time data to design a forward-thinking, active surveillance system to pragmatically study the epidemiology of vaccine failure. Our overarching goals in the proposed VAccine Failure study are to characterize post-vaccination Covid-19 clinical outcomes and identify factors associated with vaccine failure. Our central hypothesis is that adverse Covid-19 clinical outcomes after vaccination will be increasingly common over time, driven by delayed vaccination, clinical factors associated with weak or rapidly declining immune responses, and viral lineages accumulating escape mutations. We propose to identify a national longitudinal cohort of all Veterans age >65 years who had a primary care visit in the VA within the past 2 years and received at least 1 dose of any SARS-CoV-2 vaccine (N>1.55 million Veterans). We will observe these Veterans for up to 3.5 years and ascertain diagnoses of Covid-19 incidence or vaccine failure (acute SARS-CoV-2 infection + at least 1 symptom), hospitalization, and mortality. We will leverage our extensive experience conducting observational cohort studies with VA and Medicare data to emulate a target trial approach and achieve the following Aims, rooted in the epidemiological triad: Aim 1. To describe and compare Covid-19 clinical outcomes by vaccine type and manufacturer in a population-based national cohort of SARS-CoV-2 vaccinated Veterans. Aim 2. To determine environmental factors associated with vaccine failure. Aim 3. To determine host factors associated with vaccine failure. Aim 4. To determine agent factors associated with vaccine failure. To achieve Aim 4, we will use a case-control study of 600 Veterans with Covid-19 to identify cases with the outcome of viral variant and perform density sampling of controls from our SFVAHCS/VISN-21 catchment area, where we have access to banked remnant SARS-CoV-2 PCR-positive samples. This project is uniquely positioned to provide the National VA Vaccine Program with real-time evidence to rapidly adapt its vaccine delivery for Veterans (e.g., vaccine boosters for at- risk groups; timing of next-generation vaccines) while filling the urgent national need for post-vaccination surveillance in real-world settings.

随着SARS-COV-2疫苗进入质量分布，对接种疫苗的个人知之甚少 开发Covid-19（有症状疾病或“疫苗衰竭”），需要住院并死亡。辉瑞-biontech 报告了3.8次疫苗衰竭病例/1,000人年，这意味着疫苗失败将相对普遍 人口水平。辉瑞，现代和詹森疫苗效率试验涉及35,000至50,000个人 从中没有足够的数量来研究疫苗衰竭，要求进行疫苗接种后的监测 现实世界中的观察队列研究。使用VHA公司数据仓库（CDW）和 COVID-19共享数据资源，我们可以利用实时数据来设计一种前瞻性，主动 监视系统务实研究疫苗衰竭的流行病学。我们在 拟议的疫苗衰竭研究是为了表征疫苗接种后的临床结局和 确定与疫苗衰竭相关的因素。我们的中心假设是不利的Covid-19临床 疫苗后的结果随着时间的推移将越来越普遍，由延迟的疫苗驱动 与免疫反应弱或快速下降的因素以及病毒谱系累积逃生有关的因素 突变。我们建议确定所有年龄> 65岁的退伍军人的国家纵向队列 在过去的两年中，VA的初级保健访问，并至少接受1剂SARS-COV-2疫苗 （n> 155万退伍军人）。我们将观察这些退伍军人长达3.5年，并确定 COVID-19发病率或疫苗衰竭（急性SARS-COV-2感染 +至少1个症状），住院和 死亡。我们将利用我们通过VA进行观察队列研究的丰富经验 Medicare数据模拟目标试验方法并实现以下目标，植根于流行病学 三合会：目的1。描述和比较疫苗类型的COVID-19临床结果和制造商 以人群为基础的SARS-COV-2疫苗接种退伍军人队列。目标2。确定环境 与疫苗衰竭相关的因素。目标3。确定与疫苗衰竭相关的宿主因素。目的 4。确定与疫苗衰竭相关的药物因子。为了实现目标4，我们将使用一个案例对照 研究600名具有COVID-19的退伍军人，以识别病毒变体结果的病例并执行密度 从我们的SFVAHCS/VISN-21集水区中对控件进行采样 SARS-COV-2 PCR阳性样品。该项目的独特位置可以提供国家弗吉尼亚州疫苗 具有实时证据的计划，可以快速调整其对退伍军人的疫苗输送（例如，用于AT-的疫苗助推器 风险群体；下一代疫苗的时机）同时满足了疫苗后的紧急国家需求 现实环境中的监视。