PT  - JOURNAL ARTICLE
AU  - Ashley K Clift
AU  - Adam von Ende
AU  - Pui San Tan
AU  - Hannah M Sallis
AU  - Nicola Lindson
AU  - Carol A C Coupland
AU  - Marcus R Munafò
AU  - Paul Aveyard
AU  - Julia Hippisley-Cox
AU  - Jemma C Hopewell
TI  - Smoking and COVID-19 outcomes: an observational and Mendelian randomisation study using the UK Biobank cohort
AID  - 10.1136/thoraxjnl-2021-217080
DP  - 2022 Jan 01
TA  - Thorax
PG  - 65--73
VI  - 77
IP  - 1
4099  - http://thorax.bmj.com/content/77/1/65.short
4100  - http://thorax.bmj.com/content/77/1/65.full
SO  - Thorax2022 Jan 01; 77
AB  - Background Conflicting evidence has emerged regarding the relevance of smoking on risk of COVID-19 and its severity.Methods We undertook large-scale observational and Mendelian randomisation (MR) analyses using UK Biobank. Most recent smoking status was determined from primary care records (70.8%) and UK Biobank questionnaire data (29.2%). COVID-19 outcomes were derived from Public Health England SARS-CoV-2 testing data, hospital admissions data, and death certificates (until 18 August 2020). Logistic regression was used to estimate associations between smoking status and confirmed SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death. Inverse variance-weighted MR analyses using established genetic instruments for smoking initiation and smoking heaviness were undertaken (reported per SD increase).Results There were 421 469 eligible participants, 1649 confirmed infections, 968 COVID-19-related hospitalisations and 444 COVID-19-related deaths. Compared with never-smokers, current smokers had higher risks of hospitalisation (OR 1.80, 95% CI 1.26 to 2.29) and mortality (smoking 1–9/day: OR 2.14, 95% CI 0.87 to 5.24; 10–19/day: OR 5.91, 95% CI 3.66 to 9.54; 20+/day: OR 6.11, 95% CI 3.59 to 10.42). In MR analyses of 281 105 White British participants, genetically predicted propensity to initiate smoking was associated with higher risks of infection (OR 1.45, 95% CI 1.10 to 1.91) and hospitalisation (OR 1.60, 95% CI 1.13 to 2.27). Genetically predicted higher number of cigarettes smoked per day was associated with higher risks of all outcomes (infection OR 2.51, 95% CI 1.20 to 5.24; hospitalisation OR 5.08, 95% CI 2.04 to 12.66; and death OR 10.02, 95% CI 2.53 to 39.72).Interpretation Congruent results from two analytical approaches support a causal effect of smoking on risk of severe COVID-19.Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. The individual participant data from UK Biobank is available on application by bona fide researchers to the UK Biobank (via the Access Management Team). Individual level data is not permitted to be shared by the authorship team. A data dictionary defining ICD-10 codes used to define comorbidities, or Read/SNOMED codes to define smoking exposures from primary care data, can be made available on request to the corresponding author.