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

Joshua Elliott,Ioanna Tzoulaki,Matthew Whitaker,Cyrille Delpierre,Barbara Bodinier,Marc Chadeau-Hyam,Roel Vermeulen,Paul Elliott

doi:10.1007/s10654-021-00722-y

Abstract

Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18–3.49] per S.D. [8.1 years], p = 2.6 × 10–17), male sex (OR = 1.47 [1.26–1.73], p = 1.3 × 10–6) and Black versus White ethnicity (OR = 1.21 [1.12–1.29], p = 3.0 × 10–7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin–angiotensin–aldosterone system inhibitors may be explained by the aforementioned factors.

Highlights

Coronavirus disease 2019 (COVID-19) was first documented in the UK at the end of January 2020, with possible community transmission likely to have started earlier [1]
Male sex and Black ethnicity were strongly associated with COVID-19 death as previously reported [5, 6] and were highly explanatory of COVID-19 death
Comorbidities, history of oral steroids and being a healthcare worker, current smoker or former drinker at enrolment were independently associated with COVID-19 death

Summary

Introduction

Coronavirus disease 2019 (COVID-19) was first documented in the UK at the end of January 2020, with possible community transmission likely to have started earlier [1]. We investigate risk factors for COVID-19 and non-COVID-19 death since January 2020 using the latest mortality data linked to UK Biobank (to 21 September 2020) and quantify their independent and joint contribution to COVID-19 mortality through sequential adjustment and variable selection approaches. We considered six categories of variables potentially associated with COVID-19 mortality: demographic, social, health risk, biological, medical, and environmental factors [32] (Supplementary Methods). As a complementary analysis accounting for correlation between covariates, we used logistic LASSO (penalised) regression This approach aimed to identify a parsimonious set of variables jointly explaining risk of COVID-19 or non-COVID-19 death, as well as estimating their joint (and mutually-adjusted) effects [35]. All analyses were performed in R, version 4.0.2

Results

A Demographics

Discussion

Compliance with ethical standards