Characterization of Persistent COVID-19

PROJECT SUMMARY Immunosuppressed individuals are increasingly recognized as a focal point of the COVID-19 epidemic. They are at increased risk of chronic COVID-19 infection, therapeutic treatment failure, severe disease and COVID-19 mortality. Evidence is also emerging that they may also be drivers of COVID-19 variant/subvariant emergence, due to their risk of prolonged infection and accelerated viral evolution. However, the immune and viral mechanisms by which chronic infection, viral evolution, and drug resistance occur in this population are poorly understood. To improve health outcomes for this high-risk population and to reduce the risk of viral evolution and drug resistance, there is an urgent need to address gaps in our understanding of which immune deficiencies increase the risk of chronic COVID-19 infection and accelerated viral evolution. The primary goal of this proposal is to determine the host and virologic characteristics that promote chronic viral infection and viral evolution. The proposing investigators will an existing translational research infrastructure with experience recruiting cohorts of immunosuppressed individuals with COVID-19 and broad expertise in clinical research, viral quantification, viral culture, sequencing, and immunology. The results will provide critical new data about COVID-19 pathogenesis, variant evolution, therapeutic response, and inform the clinical care of immunosuppressed populations. By deepening our understanding of the immune pathways of viral clearance, the results from this proposal may also identify potential targets for the next generation of vaccines and therapeutics.