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

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Wang, Qingning 
Codd, Veryan 
Raisi-Estabragh, Zahra 
Musicha, Crispin 
Bountziouka, Vasiliki 


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.



Aged, Biological Specimen Banks, COVID-19, Cohort Studies, Female, Humans, Leukocytes, Male, Mendelian Randomization Analysis, Middle Aged, Risk Factors, SARS-CoV-2, Telomere, United Kingdom

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Elsevier BV
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
Medical Research Council (MR/M012816/1)
British Heart Foundation (RG/18/13/33946)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
British Heart Foundation (CH/12/2/29428)
National Institute for Health and Care Research (IS-BRC-1215-20014)
UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.
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