Mapping Immune Responses to CMV in Renal Transplant Recipients - Mechanistic Assays Core

ABSTRACTThe COVID-19 clinical syndrome caused by the SARS-CoV-2 virus has the potential to cause significantmorbidity and mortality in previously healthy patients. A significant observation is that although this infectionmay result in a self-limiting upper respiratory infection or mild pneumonia in some patients, other patientsexperience progression of respiratory symptoms to requirement of intubation for mechanical respiratorysupport and death due to severe respiratory failure. This clinical observation strongly suggests that differencesin host immunologic response are the determinative factor in clinical outcome. We hypothesize that theproposed systems immunology, biostatistical and computational modeling approaches, coupled with detailedclinical phenotype of hospitalized COVID-19 patients will provide a new framework to interpret the interplaybetween SARS-CoV-2 virus and the host, and the relationship with clinical outcome. Project 1 will assess thefrequency and function of SARS-CoV-2 virus antigen specific T cells and evaluate their breadth and clonalityof their TCR repertoire with clinical outcome. Project 2 will determine epigenetic signatures of the immuneresponse to the SARS-CoV-2 virus across short, middle and long-term times and identify DNA methylation-based markers of anti-viral immunity and clinical outcome. With this approach, we will create a unique resourceof highly annotated longitudinal data on SARS-CoV-2 virus infection, which will enable the development ofnovel diagnostic strategies and therapeutics to treat or prevent SARS-CoV-2 virus infection.