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

Take Home Message

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. 

Who

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.

Length of Study

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

Results

  • 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. 

Things to Keep in Mind

  • 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. 

Author’s Conclusions

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.  

Study Design

  • 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. 

Reference

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/

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