Rho Federal Systems Division, Inc. NIAID DAIT SACCC

项目总结/摘要 SARS-CoV-2病毒已经引发了一场全球性的大流行，有超过2800万例病例， 截至2021年3月1日，美国有50万人死亡（疾病控制和预防中心，COVID Data Tracker）。美国食品和药物管理局（FDA）已向两家公司授予紧急使用授权（EUA）。 mRNA疫苗、辉瑞-BioNTech COVID-19疫苗和Moderna COVID-19疫苗。两种疫苗 使用新的mRNA脂质纳米粒递送系统，并已被证明是惊人的有效， 在大型临床试验中预防疾病。 自从在更广泛的人群中引入这些疫苗以来，已经有严重过敏反应的报道 接种这些产品。根据已发表的资料， 辉瑞-BioNTech COVID-19疫苗估计为10/1，000，000疫苗剂量，约为10- 比通常使用的疫苗所见的速度高出一倍， Moderna COVID-19疫苗报告为2.5/1，000，000。这些反应中的大多数 发生在有过敏背景的个体中，大量发生在有过敏史的个体中。 过敏反应 该项目的目的是为Rho联邦系统部门提供支持， 和临床协调中心，负责方案制定、实施、数据分析和报告 一项具有两个主要目的的多中心、随机、初始设盲、II期研究的结果。一是 估计对辉瑞BioNTech和Moderna COVID-19的全身过敏反应的比例 对食物、毒液、药物或疫苗有严重过敏反应史的个体接种疫苗（高- 过敏[HA]）或肥大细胞疾病（MCD）病史。第二，如果HA/MCD人群的风险是 是为了确定HA/MCD人群中的比例是否高于 非特应性研究人群。如果对以下任何一种药物发生大量的立即全身过敏反应， 或者两种疫苗都被看到，本研究的另一个重点是开始评估过敏的机制。 对COVID-19疫苗的反应，并确定是否可以通过患者病史确定特定的风险因素 或生物标记物检测。 这些信息将是至关重要的，以适当建议高度过敏的个人和那些与肥大细胞疾病 关于这些疫苗，保持公众对这些疫苗安全性的信任，并尽量减少疫苗接种。 对这些和未来使用这种新技术的疫苗犹豫不决。

PROJECT SUMMARY / ABSTRACT The SARS-CoV-2 virus has triggered a world-wide pandemic with over 28 million cases and more than 500,000 deaths in the United States as of March 1, 2021 (Centers for Disease Control and Prevention, COVID Data Tracker). The Food and Drug Administration (FDA) has given Emergency Use Authorization (EUA) to two mRNA vaccines, the Pfizer-BioNTech COVID-19 Vaccine and the Moderna COVID-19 Vaccine. Both vaccines use the new mRNA lipid nanoparticle delivery system and have been proven to be strikingly effective in preventing disease in large clinical trials. Since introduction of these vaccines in a wider population, there have been reports of severe allergic reactions to vaccination with these products. According to published sources, the incidence rate of anaphylaxis for the Pfizer-BioNTech COVID-19 Vaccine is estimated at 10/1,000,000 vaccine doses, which is approximately 10- fold higher than the rate typically seen with commonly used vaccines, and the rate of anaphylaxis for the Moderna COVID-19 Vaccine has been reported as 2.5/1,000,000. The majority of these reactions have occurred in individuals with an allergic background and a large number in individuals with a history of anaphylaxis. The purpose of this project is to provide support for Rho Federal Systems Division to serve as the Statistical and Clinical Coordinating Center for protocol development, implementation, data analysis, and reporting of results for a multicenter, randomized, initially blinded, phase 2 study with two principal aims. The first is to estimate the proportions of systemic allergic reactions to the Pfizer-BioNTech and the Moderna COVID-19 vaccines in individuals with a history of severe allergic reactions to foods, venoms, drugs, or vaccines (High- Allergy [HA]), or a history of mast cell disorders (MCD). The second, if the risk in the HA/MCD population is demonstrable, is to determine whether the proportions are higher in the HA/MCD population compared to a non-atopic study population. In the event a significant number of immediate systemic allergic reactions to either or both vaccines are seen, another focus of this study is to begin evaluating the mechanism(s) of allergic reactions to the COVID-19 vaccines, and to determine if specific risk factors can be identified by patient history or biomarker testing. This information will be crucial to properly advise highly allergic individuals and those with mast cell disorders regarding these vaccines, to maintain public trust in the safety of these vaccines, and to minimize vaccine hesitancy for these and future vaccines using this new technology.