The overall goal of the parent U54 on which this supplement is based is to understand the underpinning of the immune response to COVID-19 infection and vaccination in immunocompromised patients with Autoimmune Disorders (AID) and malignancy (B cell and plasma cell malignancies and NSCLC). We have made significant progress in recruiting and analyzing vaccine responses in immunocompromised patients (IC) with AID and malignant disorders with major emphasis on anti-B cell therapy and immune checkpoint blockade (ICB) therapies in B cell and plasma cell malignancies and NSCLC, respectively. For all cohorts we have obtained serologic data and neutralization titers. While overall there is decreased efficacy of current vaccination schedules in IC populations, there is significant heterogeneity, both class differences between diseases and IS regimens, as well as inter-individual differences. Both the cellular basis of this variation and the immunological basis of booster variability in IC populations remain to be determined. In this supplemental application, we will conduct a comprehensive analysis of the efficacy and immunological determinants of efficacy of boosters in our-preexisting populations and samples. AND This U54 supplement from Emory University is a part of the 11 SeroNet institutions involved in the Pooling Project with the lead institution: Cedars-Sinai Medical Center. The goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in these vulnerable populations. We will harmonize efforts and analyses of individual-level data in immunocompromised populations to assess effectiveness of vaccine boosters and immune responses using data from 11 Serological Sciences Network (SeroNet) institutions. Emory will be providing prospective data from patients with lung cancer, hematologic malignancies, solid organ transplant, and autoimmune diseases and lead the analysis in patients with autoimmune diseases.

Narrative for Overall: The Emory SeroNet U54 program brings together a multidisciplinary team of scientists to address unmet needs relating to protective immunity against SARS CoV-2 infection. The team has a long track record of studies in viral, tumor- and autoimmunity, and will examine the nature and regulation of SARS-CoV-2 immunity in patients with autoimmunity and cancer. These studies will also provide basic insights into determinants of protective anti-viral immunity and risk of SARS-CoV-2 related immunopathology.