Older biological age is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank

Background Older chronological age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain, however, whether older biological age, as assessed by leucocyte telomere length (LTL), is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 131 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6,775 participants in UKB who had tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·31; P=0·004) per 1-SD shorter usual LTL, after adjustment for chronological age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL, indicative of older biological age, is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including chronological age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.