Smoking and COVID-19 Infection and Related Mortality: A Prospective Cohort Analysis of UK Biobank Data

Albert Prats-Uribe,1 Junqing Xie,1 Daniel Prieto-Alhambra,1 Irene Petersen2,3 1Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine - Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK; 2Department of Primary Care and Population Health, UCL, London, NW3 2PF, UK; 3Department of Clinical Epidemiology, Aarhus University, Aarhus N, 8200, DenmarkCorrespondence: Daniel Prieto-AlhambraPharmaco- and Device Epidemiology, Centre for Statistics in Medicine - Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD, UKEmail daniel.prietoalhambra@ndorms.ox.ac.ukBackground: Several papers have shown contradictory evidence about the relationship between smoking and COVID-19-related deaths. There is little evidence about smoking and risk of infection. We aim to examine association between smoking and COVID-19 infection and subsequent mortality.Methods: This was a prospective study with participants from the UK Biobank cohort. Participants who lived in England were followed up from 01/02/2020 to 28/06/2020 with data linked to hospital episode statistics, Office for National Statistics and Public Health England PCR tests. We compared current-smokers, previous-smokers with never-smokers and estimated risk ratio (RR) of COVID-19 infection and subsequent mortality using Poisson regression adjusting for age, sex, ethnicity, body mass index and socio-economic status. Interactions between smoking status and age and sex were tested for using multiplicative interactions, and analyses were stratified by median age (49– 68 years, 69– 86 years) and sex.Results: In total, 402,978 participants were included in the analyses. The majority were never smokers, 226,294 (56.2%), 140,090 (34.8%) were previous smokers, and 39,974 (9.9%) current smokers. COVID-19 infection was identified in 1591 (0.39%) people, and 372/1591 (23.4%) died. Amongst the younger participants, smokers were nearly twice as likely to become infected with COVID-19 than never smokers (RR 1.88 [1.49– 2.38]) whereas there was no difference for those aged 69+ (RR 1.05 [0.82– 1.34]). In contrast, amongst the older participants, smokers were twice as likely to die from COVID-19 compared to non-smokers (RR 2.15 [1.11– 4.16]) whereas there was no difference for those under the age of 69 (RR 1.22[0.83– 1.79]). Similar patterns were observed for previous smokers. The impact of smoking was similar in men and women.Conclusion: The association between smoking and COVID-19 infection and subsequent death is modified by age. Smokers and previous smokers aged under 69 were at higher risk of COVID-19 infection, suggesting the risk is associated with increased exposure to SARS-COV-2 virus. Once infected, older smokers were twice as likely to die from COVID-19 than never smokers, possibly mediated by increased risk of chronic conditions/illnesses.Keywords: smoking, COVID-19, UK Biobank