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

Abstract

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.

Accelerated ageing is associated with increased COVID-19 severity and differences across ethnic groups may exist

“…This likely explains a lot of the association between TL and COVID-19 severity shown within these models and is possibly as a result of the established link between telomeres and these covariates. Firstly, age has been shown to negatively affect TL, with older age linked to shorter telomeres (12). Secondly, smoking has also been shown to negatively affect TL and likewise, so have the comorbidities; type 2 diabetes and obesity (30)(31)(32).…”

“…Secondly, immunosenescence is another process linked with accelerating ageing and short telomeres. Individuals with short telomeres have a reduced T cell proliferation ability and a higher proportion of senescent T cells (12,43). This issue is then exacerbated by COVID-19, which is known to cause T cell lymphopenia (43).…”

“…Secondly, telomere length (TL) has been proposed as a biomarker for biological age due to its connection to cellular proliferative capacity and its association with age (10)(11)(12). Telomeres are repetitive sections of nucleoprotein structures found at the ends of chromosomes which ensure genome integrity (13).…”

“…This is because after telomeres reach critical length, the cells enter into senescence and are unable to replicate (14). Again, while an association between shorter telomeres and severe COVID-19 outcomes has been shown, it has not been truly studied within ethnicities (12).…”

Potential Physiological and Cellular Mechanisms of Exercise That Decrease the Risk of Severe Complications and Mortality Following SARS-CoV-2 Infection

“…This context is associated with better survival from sepsis and lower severity of ARDS [ 175 ]. Recently, shorter leukocyte telomere length was found to be associated with a higher risk of adverse COVID-19 outcomes, independent of other major risk factors, including chronological age [ 176 , 177 ]. As reviewed by Garatachea [ 178 ], habitual PA, especially aerobic exercise, as well as good cardiorespiratory fitness, is associated with longer leukocyte telomere length.…”