The Long Life Family Study

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Abstract The Long Life Family Study (LLFS) is a cohort of unusually healthy individuals who show longer health spans and marked delays in the onset of dementia, heart disease and stroke. The LLFS participants also show enrichment in Healthy Aging Phenotypes (HAPs) that include several biological domains such as exceptional memory, grip strength, pulmonary function, blood pressure, and/or metabolism. Since LLFS recruited families showing familial clustering of longevity, even the younger participants may have protective factors that give them increased probability of obtaining exceptional longevity themselves. However, exposure to the SARS-CoV-2 virus may quite possibly be an important risk/protective factor determinant of future health for the LLFS participants. In particular, evidence suggests there may be long term increased CVD risk such as myocarditis and stroke or cognitive impairment in affected survivors. This proposal seeks to augment the existing strengths of LLFS, which include longitudinal detailed phenotyping and serial multi-omics assays to identify risk for various health outcomes by conducting an antibody test for exposure to the SARS-CoV-2 and help classify LLFS participants as symptomatic individuals diagnosed with COVID-19 infection, asymptomatic carriers of COVID- 19 infection, as well as those who did not have COVID-19 infection or the disease. Till date, SARS-CoV-2 antibody studies have focused almost exclusively on blood based antibody responses and mucosal immunity in the naso- and oro-pharyngeal areas, the primary sites of SARS-CoV-2 infection, remain poorly understood. Hence, this study will measure SARS-CoV-2 antibodies in saliva to minimize risk to participants and provide an estimate of mucosal immunity in this population. Specifically, this administrative supplement will measure different isotypes of SARS-CoV-2 antibodies (IgG and IgA) in saliva (Aim 1) and also measure quantitative levels of both these antibody isotypes (Aim 2). We will accomplish both aims by using a self collected saliva sample analyzed using an in-house SARS-CoV-2 ELISA assay and a commercially available FDA-EUA approved assay (Roche Inc.) that will be able to differentiate between SARS-CoV-2 antibodies produced due to natural infection or vaccination. We will use family based multivariate generalized linear models to test for associations of SARS- CoV-2 antibodies (isotypes and quantitative levels) with both aging trajectories as well as with subsequent follow- up data on morbidity and mortality. This approach will allow us to estimate the independent contribution of SARS-CoV-2 antibodies to outcomes of interest, after controlling for other, known risk factors and measures (including various OMICs). Thus, identifying LLFS participants who were exposed to SARS-CoV-2 infection will provide an opportunity to evaluate the effect of SARS-CoV-2 infection on the trajectories of several HAPs that are enriched in LLFS, future health events and overall health span of LLFS participants.