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Smoking and COVID-19 outcomes: an observational and Mendelian randomisation study using the UK Biobank cohort

Abstract:

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.

Publication status:
Published
Peer review status:
Peer reviewed

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Files:
Publisher copy:
10.1136/thoraxjnl-2021-217080

Authors


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Institution:
University of Oxford
Division:
MSD
Department:
Primary Care Health Sciences
Role:
Author
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Role:
Author
ORCID:
0000-0003-0000-5664


Publisher:
BMJ
Journal:
Thorax More from this journal
Volume:
77
Issue:
1
Pages:
65-73
Publication date:
2021-09-27
Acceptance date:
2021-06-14
DOI:
EISSN:
1468-3296
ISSN:
0040-6376


Language:
English
Keywords:
Pubs id:
1196112
Local pid:
pubs:1196112
Deposit date:
2021-09-28

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