University of Rochester Intellectual and Developmental Disabilities Research Center

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ABSTRACT School-children with intellectual and developmental disabilities (IDD) are at acute risk for severe COVID-19. Many have compromised immunological and respiratory function, cognitive impairment and complex medical issues. Children with IDD desperately need to attend specialized schools, but this also places them at ultra-high risk of COVID-19 exposure and infection, despite masking, distancing, and vaccination of staff. Critically, we lack longitudinal data on development and persistence of antibody-mediated immunity to COVID-19 for children and staff in IDD-specialized schools, including cross-strain protection, to guide development of vaccination and policy recommendations. This supplement brings together the strengths of the University of Rochester Intellectual and Developmental Disabilities Center and the UR RADx-UP. Under this Administrative Supplement, we propose continuation of our prospective, longitudinal tracking of anti-SARS-CoV-2 antibodies in over 56 IDD students and 282 staff at a specialized school for IDD children. Via RADx-UP, we currently have 7 monthly capillary blood samples per subject analyzed for anti-spike (S) and anti-nucleoprotein (N) IgG against SARS-CoV-2 and variants, and common coronavirus strains (HCoVs: OC43, HKU1, NL63, 229E) measured by the mPLEX-CoV research assay. We will extend this prospective, longitudinal study with an additional 12 months of sampling to capture increases and decreases in SARS-CoV-2 antibody levels. In Aim 1 we will use multidimensional measurement of anti-SARS-CoV-2 and other coronavirus antibodies over 1 year to estimate the rate at which antibodies decrease after vaccination and infection. We will use memory B cell studies to estimate long-lived immune memory and multidimensional analysis of IgG immune repertoire against SARS- CoV-2 variants. In Aim 2, we will link these data, with a comprehensive immune response genotypic and IDD phenotypic analysis. Targeted resequencing of vaccine response genes will provide critical information on immune response associated gene mutations (e.g. cytokine promoter polymorphisms) in neurotypical staff and IDD children, and their influence on anti-SARS-CoV-2 antibody levels. Successful completion of this project will identify decay rates of anti-SARS-CoV-2 IgG in vaccinated subjects, and provide new data on association of IDD phenotyping and immune gene SNPs with vaccine responses.