Genetic and phenotypic analysis of the causal relationship between aging and COVID-19

Epidemiological studies revealed that the elderly and those with comorbidities are most affected by COVID-19, but it is important to investigate shared genetic mechanisms between COVID-19 risk and aging. We conducted a multi-instrument Mendelian Randomization analysis of multiple lifespan-related traits and COVID-19. Aging clock models were applied to the subjects with different COVID-19 conditions in the UK-Biobank cohort. We performed a bivariate genomic scan for age-related COVID-19 and Mendelian Randomization analysis of 389 immune cell traits to investigate their effect on lifespan and COVID-19 risk. We show that the genetic variation that supports longer life is significantly associated with the lower risk of COVID-19 infection and hospitalization. The odds ratio is 0.31 (P = 9.7 × 10−6) and 0.46 (P = 3.3 × 10−4), respectively, per additional 10 years of life. We detect an association between biological age acceleration and future incidence and severity of COVID-19 infection. Genetic profiling of age-related COVID-19 infection indicates key contributions of Notch signaling and immune system development. We reveal a negative correlation between the effects of immune cell traits on lifespan and COVID-19 risk. We find that lower B-cell CD19 levels are indicative of an increased risk of COVID-19 and decreased life expectancy, which is further validated by COVID-19 clinical data. Our analysis suggests that the factors that accelerate aging lead to an increased COVID-19 risk and point to the importance of Notch signaling and B cells in both. Interventions that target these factors to reduce biological age may reduce the risk of COVID-19. Older adults and those with comorbidities are more likely to develop severe COVID-19 if infected with SARS-CoV-2. In this study, we investigate the genetic factors underlying the link between aging and COVID-19. Using data on the genetic variation between individuals and statistical methods to allow us to determine causality, we find that genetic variation associated with longer lifespan is associated with reduced risk of COVID-19 infection and hospitalization. We also find that acceleration of biological age (i.e., the age of your body based on physiological measurements rather than time) is associated with future incidence and severity of COVID-19, and identify some of the key cells and molecules involved in aging-related COVID-19 risk. Our study helps to characterize the relationship between aging and COVID-19, which may help to identify strategies to protect or treat older adults. Ying et al. conduct a multi-instrument Mendelian randomization study looking at the link between aging and COVID-19 risk. They observe an association between genetic variation implicated in longevity and decreased risk of COVID-19 infection and hospitalization, with Notch signaling and immune system development loci found to be important in aging-related COVID-19 risk.