CD4+ T cells and B cells are critical to generate high-affinity antibodies against most pathogens, and antigen-presenting cells such as dendritic cells and macrophage are essential in delivering antigen to the lymph nodes to generate long-lived cellular and humoral immunity. As immunocompromised individuals often have deficiencies or abnormalities in one or more immune cell populations, we hypothesize that analysis of immunocompromised patients with deficiencies/abnormalities in distinct cellular compartments (eg. plasma cells in multiple myeloma; CD4+ T cells in people living with HIV; lymphocytes in chronic lymphocytic leukemia) will be able to define the role of a given immune cell type on generation of durable protective immunity against SARS-CoV-2. Moreover, these comparative analyses may further identify specific gaps in SARS-CoV-2 immunity within different immunocompromised populations that may be complemented with therapies. Through our funded U54 parent grant, we have established several cohorts of immunocompromised populations, including people living with HIV and patients with various hematologic and solid tumor cancer malignancies. In addition, we have developed a comprehensive immune analysis platform that integrates measures of cellular and humoral immunity that will allow us to perform comparative analyses of cellular and humoral immunity across multiple immunocompromised patient populations.