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

J Gerontol A Biol Sci Med Sci. 2021 Jul 13;76(8):e133-e141. doi: 10.1093/gerona/glab060.


Background: Age and disease prevalence are the 2 biggest risk factors for Coronavirus disease 2019 (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 2 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 preexisting diseases/conditions.

Results: Six hundred and thirteen 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 (ORMortality = 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 preexisting diseases/conditions at baseline (ORM = 1.50, 95% CI: 1.30-1.73 per 5 years, p = 3.1 × 10-8) and at the early pandemic (ORM = 1.21, 95% CI: 1.04-1.40 per 5 years, p = .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.

Keywords: Biological age; Biomarkers; Phenotypic age; UK Biobank.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / physiology*
  • Biological Specimen Banks*
  • Biomarkers
  • COVID-19 / epidemiology*
  • COVID-19 Testing / statistics & numerical data*
  • Chronic Disease
  • Humans
  • Middle Aged
  • Models, Statistical
  • Mortality / trends*
  • Preexisting Condition Coverage / statistics & numerical data
  • SARS-CoV-2 / isolation & purification
  • Severity of Illness Index*
  • Time Factors
  • United Kingdom / epidemiology


  • Biomarkers