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Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank
Qingning Wang1, Veryan Codd1, Zahra Raisi-Estabragh2
1Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.
Insights
Shorter leucocyte telomere length (LTL), a marker of biological age, is associated with increased risk of severe COVID-19 outcomes. This finding holds true even when accounting for age and other major risk factors.
Area of Science:
- Genetics and Aging Research
- Infectious Disease Epidemiology
- Biomarker Discovery
Background:
- Older age is the primary risk factor for severe COVID-19.
- Leucocyte telomere length (LTL) is a proposed marker of biological aging.
- The association between LTL and COVID-19 outcomes remains unclear.
Purpose of the Study:
- To investigate the association between LTL and adverse COVID-19 outcomes.
- To explore potential causal links using Mendelian randomization.
Main Methods:
- Utilized UK Biobank data from 2006-2010 for LTL measurements.
- Analyzed COVID-19 outcomes (hospitalization, critical care, mortality) up to November 2020.
- Conducted Mendelian randomization with 130 LTL-associated genetic variants.
Main Results:
- Shorter LTL was significantly associated with increased odds of adverse COVID-19 outcomes (OR 1.17 per 1-SD shorter LTL).
- This association remained significant after adjusting for age, sex, ethnicity, and other risk factors.
- Mendelian randomization analyses showed a concordant but non-significant trend.
Conclusions:
- Shorter LTL is independently associated with a higher risk of adverse COVID-19 outcomes.
- Further research is required to establish causality between LTL and COVID-19 severity.
Abstract:
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.