Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed leukemia in the Western world and disproportionately affects older adults. Although there have been observational studies that have highlighted the susceptibility of CLL patients to viral infections such as COVID-19, a deeper understanding of this susceptibility is needed in order to develop new treatment strategies. The research team will leverage samples and data collected in an extensive Institute for Systems Biology/Swedish Medical Center COVID-19 trial to investigate the urgent and often fatal problem of viral infections in CLL patients through orchestrating single-cell multi-omics and a collection of novel systems biology computational approaches. The research aims to provide an improved understanding of how the altered epigenetic landscape and transcriptional reprogramming in CLL patients influences the activation, differentiation, and function of immune cells upon COVID-19 infection, and how these dysregulated processes lead to a compromised anti-viral response.