The ImmuneRACE Study: A Prospective Multicohort Study of Immune Response Action to COVID-19 Events with the ImmuneCODE™ Open Access Database

ABSTRACT Objectives The primary aim of this study is to increase our understanding of the adaptive immune response to the SARS-CoV-2 virus by assaying the peripheral immune repertoire for virus-associated T-cell receptors (TCRs). Secondary aims include identification and characterization of SARS-CoV-2–specific B-cell receptors (BCRs) and monoclonal antibodies (mAbs) generated by antibody-producing cells during and after acute infection. Trial design ImmuneRACE is a prospective, single group, multi-cohort, exploratory study of unselected eligible participants exposed to, infected with, or recovering from SARS-CoV-2. Participants Approximately 1000 individuals, aged 18 to 89 years and residing in 24 different geographic areas within the United States, will be enrolled, primarily using remote telemedicine technologies. Cohorts will be based on clinical history. Cohort 1 will include participants exposed to SARS-CoV-2 within 2 weeks of study entry. Cohort 2 participants will include those clinically diagnosed or with positive laboratory confirmation of active COVID-19 disease. Cohort 3 will comprise participants previously diagnosed with COVID-19 disease who have been deemed recovered based on two consecutive negative tests, clearance by a healthcare professional, or resolution of symptoms related to COVID-19. All participants must be able to communicate with the investigator and understand and comply with the requirements of the study. Protected populations and those who may not safely participate are not eligible for this study. Intervention and comparator Blood samples and nasopharyngeal or oropharyngeal swabs will be collected from participants. Nasopharyngeal or oropharyngeal swabs will be collected by inserting a swab into the nose or throat of the participant. Samples will be shipped frozen or transported refrigerated or at room temperature to Adaptive Biotechnologies for processing, including, but not limited to, testing for coronavirus or other respiratory illnesses, DNA extraction, and TCR analysis. The immunoSEQ assay will be conducted using DNA extracted from blood samples. An electronic questionnaire will be administered to collect information pertaining to the participant’s medical history, symptoms, and diagnostic tests performed for COVID-19 disease. Participants will have the option to undergo additional blood draws and questionnaires over a 2-month period. In collaboration with Microsoft, we will use machine learning and artificial intelligence approaches to construct a classifier based on TCR repertoire data designed to accurately distinguish COVID-19–positive cases from unexposed controls (from the ImmuneCODE database of TCR sequences). A rigorous statistical analysis will be performed to validate the classifier. Main outcomes The main outcomes of this study will include a comparison of disease-specific TCR signatures in patients and controls, identification of the immunodominant antigens that elicit a T-cell response to SARS-CoV-2, risk stratification based on an individual’s immune signature, and determination of immune signatures of patients exposed to SARS-CoV-2 that may allow earlier detection of infection compared to available tests. Trial registration “ImmuneRACE – Immune Response Action to COVID-19 Events (Protocol ADAP-006, version 1.0; 5/8/2020) is registered with the US National Institutes of Health and can be accessed at ClinicalTrials.gov ( NCT04494893 ).