Clonal hematopoiesis and severity of COVID-19 disease

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SUMMARY COVID-19 disease has a diverse range of outcomes, and this individual-to-individual variability is poorly understood. Clonal hematopoiesis is a prevalent, age-associated condition that arises from the accumulation of various somatic mutations in hematopoietic cells and can lead to their clonal amplification. These mutant clones corrupt immune cell function and contribute to mortality and increased cardiovascular disease risk through cytokine dysregulation. The proposed research will investigate the hypothesis that clonal hematopoiesis is a hematologic host factor that predisposes persons to develop severe COVID-19 disease. Through a collaborative effort between Kenneth Walsh Ph.D. (UVA) and Christopher deFilippi M.D. (Inova) the proposed research will explore the possibility that clonal hematopoiesis-mediated alterations to the immune system are associated with clinical laboratory measures of a marked inflammatory response, biochemical evidence of cardiac injury and poor clinical outcomes in patients with COVID-19 infection. Patients will be consented and enrolled at the Inova hospital system in northern Virginia that delivers service to more than 2 million people per year in the Washington, D.C metro area with a large volume of hospitalized COVID-19 positive patients. Upon enrollment, biospecimens will be collected and banked. Clinical data will be extracted from the electronic medical record and stored in research form in Research Electronic Data Capture software. DNA will be sent to Dr. Walsh’s laboratory at UVA for analysis of clonal hematopoiesis. DNA from the Inova group will be processed at UVA to assess clonal hematopoiesis via targeted, error-corrected DNA sequencing. This analysis employs an enrichment panel to capture driver genes of interest and the construction of libraries with DNA barcodes. Following deep next generation DNA sequencing, a bioinformatic platform is employed to distinguish true variant calls from noise at a particular exonic location. These data on clonal hematopoiesis will then be shared with the team at Inova to test whether there are associations between somatic mutations, clinical outcome, and markers of inflammation and cardiac injury.