COVID-19 Administrative Supplement for FOXO3 Genotype, InflammAging, Cardiovascular Disease, and Dementia. Kuakini Hawaii Lifespan Study III

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Abstract The SARS-CoV-2 virus that causes COVID-19 infection is among the most serious public health challenges in the last century. However, the true prevalence of COVID-19 infection in the Hawaii community is unknown-- we do not know how widespread undiagnosed infections are, true morbidity levels, true case-fatality rates, nor whether herd immunity exists in some populations. This information may help facilitate easing of social distancing measures among other important epidemiological issues. Data from Johns Hopkins University suggest that Hawaii has one of the lowest COVID-19 infection rates in the United States (U.S.) with only 36 confirmed coronavirus cases per 100,000 persons (as of mid-April 2020). This was much lower than the U.S. national rate of 177 infections per 100,000 persons – both of which are hypothesized to be vastly underestimated, primarily due to high numbers of undiagnosed infections. One approach to help resolve these challenges is to test populations for COVID-19 antibodies (Ab). Early results from such studies in the U.S. mainland, Germany, and Holland, have found that 2% to 30% of populations have previously been infected with this coronavirus. We propose to help address these issues by sampling an underrepresented population of older Asian- Americans in Hawaii that have been well studied for other outcomes of interest (e.g. health habits, comorbidities, genetics, etc.) using a reliable Ab test that has FDA emergency use authorization (EUA) and the highest sensitivity and specificity. We propose the following Specific Aims: Primary Aim: Test the hypothesis that the prevalence rate of prior COVID-19 infection in middle-aged and elderly persons in the Japanese-American community in Hawaii will be higher than reported prevalence rates. Since the majority of persons in Hawaii tested for COVID-19 infections thus far have been symptomatic persons, we hypothesize that the actual prevalence rates of prior virus infection within this community are much higher than official reports from the Hawaii Department of Health (Hawaii Department of Health est. 36 cases per 100,000 persons in mid-April 2020). Our study sample will be drawn from a stratified random sample of over 2,000 previously recruited Kuakini Honolulu Heart Program Offspring Study (Kuakini HHP Offspring Study) participants (n=1,200; age range = 50-90 years). Exploratory Aim #1: Test the hypothesis that those with SARS-CoV-2 Ab+ (positive) tests, and who possess the longevity-associated FOXO3 and ACE-2 (anti-inflammatory) genotypes, will have experienced less severe COVID-19 related-illness (e.g. fewer overall symptoms, fewer pulmonary/cardiovascular symptoms, fewer hospitalizations, shorter duration of illness, etc.) than those with the common genotype. These study participants will be drawn from the Kuakini HHP Offspring Study cohort who test Ab positive (est. at 2%-30% of sample, i.e. 32-480 persons). Ab+ participants will be asked to complete a questionnaire detailing severity of symptoms and stratified by FOXO3 genotype. Exploratory Aim #2: Test the hypothesis that the longevity associated FOXO3 genotype and protective ACE-2 genotype will correlate with lower risk for COVID-19 infection i.e. fewer FOXO3/ACE-2 protective allele carriers will test positive for SARS-CoV-2 Ab. We hypothesize that those with the FOXO3/ACE-2 longevity-associated genotypes will be protected from COVID-19 infection.