Mapping Immune Responses to CMV in Renal Transplant Recipients - Transplant Supplement

SARS-CoV-2 virus infection and associated COVID-19 disease has caused unparalleled global morbidity andmortality in previously healthy patients, with over 4 million cases and 150,000 deaths in the US alone. Olderpatients, who experience immune dysfunction associated with aging, and patients with underlying health issues,such as chronic kidney disease, have been inequitably burdened by COVID-19. Understanding correlates ofprotection against SARS-CoV-2 infection and why these immunocompromised patients apparently possessdeficiencies in generating these protective immune responses is critical to developing clinical practices for theseat-risk populations. To address this fundamental knowledge gap, this study will characterize the natural immuneresponse to SARS-CoV-2 virus infection in immunocompromised patients and determine whether immunity islong-lasting. Specifically, we will evaluate the quantity and quality of antibodies against SARS-CoV-2 and theirrelationship to frequency and functionality of SARS-CoV-2-specific T cells, therefore generating a completepicture of the adaptive immune response to SARS-CoV-2 in immunocompromised patients.To achieve our goal, we have utilized four kidney transplant centers within the University of California to establisha cohort of 2500 patients with end-stage renal disease (ESRD) awaiting transplant and 2000 renal transplantrecipients with banked pre- and post-COVID-19 pandemic sera across a highly racially and ethnically diversepopulation, of which 40% are from minority populations that have been inequitably burdened by COVID-19. Wewill screen for exposure to SARS-CoV-2 in the complete cohort of 4500 patients, enrolling 100 ESRD and 76renal transplant recipients with evidence of SARS-CoV-2-specific antibodies, based on a recent populationseroprevalence estimate of 4% in Los Angeles. We will additionally recruit matched patients without evidence ofSARS-CoV-2-specific antibodies. Antibody titer, isotype, subclass, avidity, infection neutralization and ability tointerface with cell-mediated immunity will be determined at baseline with longitudinal follow-up 3-6 month and 9-12 months later to assess longevity of humoral immune responses to SARS-CoV-2. Similarly, we will delineatethe frequency, phenotype and longevity of SARS-CoV-2-specific cellular immune responses.This study will generate an extensive repository of clinical phenotypes, outcomes, and high-dimensional bloodand urine profiling data on longitudinal samples of patients with and without exposure to SARS-CoV-2 in theCalifornia transplant population, providing an invaluable resource for the research community in understandingimmunity to SARS-CoV-2. Utilizing state-of-the-art biostatistics and computational approaches, we will integratehigh-dimensional data of humoral and cellular immune responses to develop models of combined adaptiveimmune profiles following SARS-CoV-2 exposure and assess their longevity and likelihood of protecting uponre-exposure.