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Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank

Authors: Qingning Wang 1, Veryan Codd 1, Zahra Raisi-Estabragh 2, Crispin Musicha 3, Vasiliki Bountziouka 3, Stephen Kaptoge 4, Elias Allara 5, Emanuele Di Angelantonio 6, Adam S Butterworth 6, Angela M Wood 7, John R Thompson 8, Steffen E Petersen 2, Nicholas C Harvey 9, John N Danesh 10, Nilesh J Samani 1, Christopher P Nelson 11
Published: 07/23/2021

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.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

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