Patients with hematologic malignancies appear to have a higher risk of SARS-CoV-2 infection. Disease courses are variable in severity, influenced by immunosuppression due to the malignancy and its treatment determining the degree of immune-mediated hyperinflammation implicated in lung damage, multi-organ failure, and death. This highlights the need for comprehensive clinical tests to monitor COVID19 patients, specifically, with hematologic malignancies. We propose to develop and validate two novel immuno-serological assays that will be deployed to conduct longitudinal measurement of plasma markers and peripheral blood immune cells from COVID patients with different hematologic malignancies. First, we will develop an automated 32-plexed plasma protein assay to quantify SARS-COV-2 IgG/IgM antibodies, cytokines/chemokines, angiogenesis markers, endotheliopathy markers, and pro-thrombotic markers all combined in a high-density antibody barcode array microchip. Second, we will develop a microchip assay for single-cell immune function measurement to quantify cell types and 30+ immune effector proteins in peripheral blood immune from patients. Single-cell transcriptome sequencing will be performed on select samples to cross-validate the results and reveal the mechanisms of action in COVID-induced immune activation. Third, these new assays will be deployed to measure a cohort of COVID19 patients with or without hematological malignancies and healthy donors in order to identify potential molecular correlates with immune-mediated pathology and COVID disease severity uniquely in hematological cancer patients. As the COVID19 vaccines become available, we will apply these assays to monitoring vaccine-induced humoral, cellular, and immunological response in hematological cancer patients and compare to non-cancer populations to understand differences and ways to improve the success of vaccination in patients with hematologic malignancies – a vulnerable group of patients who may not follow the same mechanisms as general populations in COVID19.