Abstract Objective Precision medicine harnesses the N-of-1 approach to detect, predict, reverse, and stop progression of disorders of aging through longitudinal observation of biomarkers with respect to genetic makeup. ABO and Rh blood group are two genetic markers that inform risk for dysglycemia, hypercortisolemia, and hypothyroidism, among others. Early in the pandemic, scientists sought to understand whether ABO and Rh blood group was also a risk factor for COVID-19 susceptibility. If proven true, the presence of mutual disease mechanisms between COVID-19 and diseases of the endocrine system may also exist. In the present study, ABO and Rh blood group was examined as a risk factor for COVID-19 susceptibility. Methods Inclusion criteria for this retrospective observational study were an active patient status in December 2019 and a record of ABO and Rh blood group on Quest Laboratory's online portal. ABO and Rh blood groups were compiled and analyzed using chi-square test, odds ratio (OR), and 95% confidence interval (CI) for association to COVID-19 susceptibility. Results 136 adult patients met inclusion criteria for this study, 44 of whom tested positive for COVID-19. The cohort was 30% female, ranging in age from 20-78 years (mean=54 years). In the COVID-19 patients, the respective frequencies of A, B, O, and AB phenotypes were 27.27%, 25. 00%, 38.64%, and 9. 09%. Of these patients, 88.64% were Rh positive. Blood group A (OR = 0.70; CI, 0.32-1.5; p > . 05), group B (OR = 1.58; CI, 0.66-3.78; p > . 05), group O (OR = 0.78; CI, 0.38-1.63, p > . 05), and group AB (OR = 2.97; CI, 0.63-13.9; p > . 05) were not significantly associated with COVID-19 susceptibility. Rh factor was also found to be an insignificant variable (OR = 2. 03; CI, 0.70-5.85; p > . 05). Discussion These findings support the growing body of literature dissociating ABO and Rh blood group from COVID-19 susceptibility. As such, it could be advised that ABO and Rh blood group is not factored into risk stratification for COVID-19 susceptibility in contrast to particular endocrine disorders. A significant limitation of this analysis is that ABO genotypes were unknown. A recent genome-wide association study confirmed a potential involvement of ABO blood group in COVID-19 clinical presentation1. Therefore, deeper analysis may also reveal the mechanistic influence of ABO genotypes on COVID-19 susceptibility, such as the type and quantity of ABO-antibodies in circulation. Further investigation is warranted to determine whether biomarkers known to inform risk of endocrine disorders also influence COVID-19 susceptibility. Understanding what governs this relationship would allow endocrinologists to develop targeted interventions to optimize an individual's health trajectory.