Rho Federal Systems Division, Inc. NIAID DAIT SACCC

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.