Biological Aging Predicts Vulnerability to COVID-19 Severity in UK Biobank Participants

Kuo, Chia-Ling; Pilling, Luke C; Atkins, Janice L; Masoli, Jane A H; Delgado, João; Tignanelli, Christopher; Kuchel, George A; Melzer, David; Beckman, Kenneth B; Levine, Morgan E

BACKGROUND: Age and disease prevalence are the two biggest risk factors for COVID-19 symptom severity and death. We therefore hypothesized that increased biological age, beyond chronological age, may be driving disease-related trends in COVID-19 severity. METHODS: Using the UK Biobank England data, we tested whether a biological age estimate (PhenoAge) measured more than a decade prior to the COVID-19 pandemic was predictive of two COVID-19 severity outcomes (inpatient test positivity and COVID-19 related mortality with inpatient test-confirmed COVID-19). Logistic regression models were used with adjustment for age at the pandemic, sex, ethnicity, baseline assessment centers, and pre-existing diseases/conditions. RESULTS: 613 participants tested positive at inpatient settings between March 16 and April 27, 2020, 154 of whom succumbed to COVID-19. PhenoAge was associated with increased risks of inpatient test positivity and COVID-19 related mortality (OR(Mortality)=1.63 per 5 years, 95% CI: 1.43-1.86, p=4.7×10 (-13)) adjusting for demographics including age at the pandemic. Further adjustment for pre-existing disease s/conditions at baseline (OR(M)=1.50, 95% CI: 1.30-1.73 per 5 years, p=3.1×10 (-8)) and at the early pandemic (OR(M)=1.21, 95% CI: 1.04-1.40 per 5 years, p=0.011) decreased the association. CONCLUSIONS: PhenoAge measured in 2006-2010 was associated with COVID-19 severity outcomes more than 10 years later. These associations were partly accounted for by prevalent chronic diseases proximate to COVID-19 infection. Overall, our results suggest that aging biomarkers, like PhenoAge may capture long-term vulnerability to diseases like COVID-19, even before the accumulation of age-related comorbid conditions.