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.
| Original language | English |
|---|---|
| Pages (from-to) | 65-73 |
| Number of pages | 9 |
| Journal | Thorax |
| Volume | 77 |
| Issue number | 1 |
| Early online date | 27 Sept 2021 |
| DOIs | |
| Publication status | Published - 31 Jan 2022 |
Data Availability Statement
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.Funding
AKC is supported by a Clinical Research Training Fellowship from Cancer Research UK (DCS-CRUK-CRTF20-AC). HMS and MRM work in a research unit funded by the UK Medical Research Council (MC_UU_00011/7). HMS is also supported by the European Research Council (grant ref: 758813 MHINT). This work was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust. PA is an NIHR senior investigator and is funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) Obesity, Diet and Lifestyle Theme and NIHR Oxford and Thames Valley Applied Research Collaboration. JHC has received grants from the National Institute for Health Research Biomedical Research Centre, Oxford, John Fell Oxford University Press Research Fund, Cancer Research UK (grant no: C5255/A18085) through the Cancer Research UK Oxford Centre, and the Oxford Wellcome Institutional Strategic Support Fund (204826/Z/16/Z). JCH is supported by a British Heart Foundation Fellowship (FS/14/55/30806), and acknowledges support from the Oxford Biomedical Research Centre, BHF Oxford Centre for Research Excellence, and Nuffield Department of Population Health. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. We are grateful to the participants of the UK Biobank as well as all the research staff who worked on the data collection and synthesis. This research has been conducted under UK Biobank application numbers 14568 and 40628.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
