Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, 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 130 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 6775 participants in UKB who 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 1·05–1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for 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 is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including 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.
【초록키워드】 COVID-19, coronavirus disease, coronavirus, Critical care, Mortality, UK biobank, Sex, risk, Biotechnology, outcome, risk factor, outcomes, Ethnicity, Coronavirus disease-19, heart, Community, age, Hospital admission, genetic variants, respiratory, exploratory, information, Causality, funding, association, marker, Analysis, Odds ratio, Respiratory Support, Composite, Biological, leucocyte, independent of, Medical Research Council, Science, higher risk, 95% CI, randomisation, foundation, participant, finding, positive, Council, independent, collider bias, MR analyses, defined, tested, evaluate, recruited, conducted, reduced, adjusted, determine, reflect, recorded, infection with SARS-CoV-2, UKB, with COVID-19, 【제목키워드】 COVID-19, cohort study, leukocyte,