COVID-19 vaccination substantially reduced morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. SeroNet has several institutions focused on conducting epidemiologic studies in immunocompromised populations using either EMR-based real-world approaches and/or building novel prospective cohorts with longitudinal assessments. When combined, there are substantive populations of patients with cancer, including hematological malignancies, solid cancers, and hematopoietic cell transplants. The cohort groups are accrued and followed prospectively for endpoints of interest and impacts of various immunotherapies/cancer treatments. In addition, there are large number of patients with autoimmune diseases, patients living with HIV and SOTR. We propose to leverage the existing infrastructure to establish the SeroNet ‘Pooling Project.’ Our general approach will be to establish a forum to coordinate a synchronized effort to pool individual-level data on immuno-compromised populations across multiple SeroNet sites. Our proposal will leverage the existing SeroNet Epi Ops and Data Ops Working Groups infrastructure to formulate a plan of action to harmonize, synchronize and transfer data across participating sites and facilitate meta-analyses of individual-level data to answer critical research questions in immunocompromised populations. We plan to facilitate parallel data harmonization and analyses on specific immunocompromised populations using a model where different sites are assigned to lead or co-leading different research questions. Lastly, we plan to disseminate results through scientific publications, adherence to data sharing policies and wider community-level communications of SeroNet findings.