Administrative Supplement for Emory SeroNet "Immune Regulation of COVID-19 Infection in Cancer and Autoimmunity"

6XPPDU\Abstract With the additional funding of this administrative supplement, we will complete projects that achieve the full extent of the research initially designated for a 5-year period. Project 1. COVID-19 infection and vaccination in autoimmunity (Sanz and Lee) We will complete additional single cell analysis of SARS-CoV-2-specific B cells and ASC in the context of booster vaccination and breakthrough infection, to add power to the initial analysis proposed for 20 total patients. We will analyze an additional 24 patients similarly split between booster and vaccination in healthy control and SLE (N=6 per group). In this validation cohort, we will perform single cell ATAC-seq analysis to integrate transcriptional and epigenetic regulatory programs. We will also analyze the contribution of B cell and ASC to the pathogenesis of long- COVID using antigen-specific flow cytometry and MENSA assays of the antibodies produced by contemporaneous antibody-secreting cells derived from a validation cohort of PASC patents and controls. As before, we will recruit PASC patients at least 90 days after resolution of the acute infection for both healthy controls and patients with SLE (N=60 each); COVID-19 recovered patients (N=30 from HC and SLE each); and 30 patients with stable SLE. This design will allow us to understand the degree of anti-viral reactivity and autoreactivity in the different groups in order to define the contributions of these features to long-COVID. Project 3. Regulation of SARS-CoV-2 immunity in cancer patients (Ahmed and Dhodapkar) We will expand our study on NSCLC patients to determine the impact of PD-1 targeted immunotherapy on the SARS-CoV-2 vaccine responses, and we will longitudinally examine the functionality of SARS-CoV-2 specific CD4+ and CD8+ T cells in NSCLC patients responding to antigen re-exposure. We will further characterize the B cell and T cell responses of patients with different lymphomas and undergoing different treatments to better understand their immune response to vaccines, and we will evaluate the immune responses to booster vaccines in MM patients receiving bispecific antibodies.