COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors 

This study of the COVID-19 epidemic and its effect on UK Biobank participants identified vitamin D, age, male sex, and Black ethnicity as key explanatory factors for COVID-19 death. However, once an adjustment for multiple risk factors was made, the association did not hold true, providing little support for a potential association. 

UK Biobank is a population-based cohort of 502,506 volunteers, aged 40 to 69 years at recruitment from 2006 to 2010. At baseline, biological measurements were recorded and touch-screen questionnaires were administered according to a standardized protocol. There were 28,956 deaths up to January  31, 2020—the date of the first recorded UK COVID-19 case—leaving N = 473,550 for the present study, among whom there have been 459 COVID-19 deaths and 2626 non-COVID-19 deaths as of September 21, 2020. These deaths were recorded through linkage to national death registries.

Deaths in the UK Biobank cohort between February 1, 2020 and September 21, 2020. 

• Age, male sex and Black ethnicity were strongly associated with COVID-19 death and were highly explanatory of COVID-19 death.  
• Comorbidities including cardiovascular disease, hypertension, diabetes and autoimmune disease as well as oral steroid use at enrolment were independently associated with increased COVID-19 mortality risk. 
• While vitamin D was associated with decreased COVID-19 mortality risk in univariate analysis, this did not survive adjustment for multiple risk factors, thus, providing little support for an association between COVID-19 mortality risk and serum vitamin D levels.  
• Previously reported associations with COVID-19 mortality involving the use of RAAS inhibitors, statins, current smoking, vitamin D levels and air pollutants may, at least partially, be explained by factors identified in this study. 

• Although UK Biobank includes over 500,000 participants, the numbers of COVID-19 deaths were modest compared to national studies of mortality and hospitalized cases. 
• While baseline characteristics of the cohort were obtained over ten years prior to the period of the epidemic, they may have changed in the interim including serum 25(OH)D levels. 
• Data from the latest release of UK Biobank include COVID-19 deaths up to the end of September 2020, and therefore do not capture the second wave of the epidemic in the UK. Inclusion of this data could provide a larger, more robust dataset. 

This study of the COVID-19 epidemic and its effect on UK Biobank participants identified age, male sex and Black ethnicity as key explanatory factors for COVID-19 death. While vitamin D was associated with decreased COVID-19 mortality risk in univariate analysis, this did not survive adjustment for multiple risk factors, thus providing little support for an association between COVID-19 mortality risk and serum vitamin D levels.  

• Risk factors were investigated for COVID-19 and non-COVID-19 deaths since January 2020 using the latest mortality data linked to UK Biobank.  
• The independent and joint contributions of the risk factors to COVID-19 deaths were quantified through sequential adjustment and variable selection approaches. 

Elliott J, Bodinier B, Whitaker M, Delpierre C, Vermeulen R, Tzoulaki I, Elliott P, Chadeau-Hyam M. COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors. Eur J Epidemiol. 2021 Mar;36(3):299-309. doi: 10.1007/s10654-021-00722-y. Epub 2021 Feb 15. PMID: 33587202; PMCID: PMC7882869.. https://pubmed.ncbi.nlm.nih.gov/33587202/