Immuno-Serological Assays for Monitoring COVID19 in Patients with Hematologic Malignancies

SUMMARYPatients with hematologic malignancies appear to have a higher risk of SARS-CoV-2 infection. Diseasecourses are variable in severity, influenced by immunosuppression due to the malignancy and its treatmentdetermining 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 thatwill be deployed to conduct longitudinal measurement of plasma markers and peripheral blood immune cellsfrom COVID patients with different hematologic malignancies. First, we will develop an automated 32-plexedplasma protein assay to quantify SARS-COV-2 IgG/IgM antibodies, cytokines/chemokines, angiogenesismarkers, endotheliopathy markers, and pro-thrombotic markers all combined in a high-density antibodybarcode array microchip. Second, we will develop a microchip assay for single-cell immune functionmeasurement to quantify cell types and 30+ immune effector proteins in peripheral blood immune frompatients. Single-cell transcriptome sequencing will be performed on select samples to cross-validate the resultsand reveal the mechanisms of action in COVID-induced immune activation. Third, these new assays will bedeployed to measure a cohort of COVID19 patients with or without hematological malignancies and healthydonors in order to identify potential molecular correlates with immune-mediated pathology and COVID diseaseseverity uniquely in hematological cancer patients. As the COVID19 vaccines become available, we will applythese assays to monitoring vaccine-induced humoral, cellular, and immunological response in hematologicalcancer patients and compare to non-cancer populations to understand differences and ways to improve thesuccess of vaccination in patients with hematologic malignancies - a vulnerable group of patients who may notfollow the same mechanisms as general populations in COVID19.