Does misclassification of former tobacco smokers explain the ‘smoker’s paradox’ in the risk of COVID-19? Insights from the Stockholm Public Health Cohort

Background: The association between tobacco smoking and the risk of COVID-19 and its adverse outcomes is controversial, as studies reported contrasting findings. Bias due to misclassification of the exposure in the analyses of current versus non-current smoking could be a possible explanation because former smokers may have higher background risks of the disease due to co-morbidity. The aim of the study was to investigate the extent of this potential bias by separating non-, former, and current smokers when assessing the risk or prognosis of diseases. Methods: We analysed data from 43,400 participants in the Stockholm Public Health Cohort, Sweden, with information on smoking obtained prior to the pandemic. We estimated the risk of COVID-19, hospital admissions and death for (a) former and current smokers relative to non-smokers, (b) current smokers relative to non-current smokers, that is, including former smokers; adjusting for potential confounders (aRR). Results: The aRR of a COVID-19 diagnosis was elevated for former smokers compared with non-smokers (1.07; 95% confidence interval (CI) =1.00–1.15); including hospital admission with any COVID-19 diagnosis (aRR= 1.23; 95% CI = 1.03–1.48); or with COVID-19 as the main diagnosis (aRR=1.23, 95% CI= 1.01–1.49); and death within 30 days with COVID-19 as the main or a contributory cause (aRR=1.40; 95% CI=1.00–1.95). Current smoking was negatively associated with risk of COVID-19 (aRR=0.79; 95% CI=0.68–0.91). Conclusions: Separating non-smokers from former smokers when assessing the disease risk or prognosis is essential to avoid bias. However, the negative association between current smoking and the risk of COVID-19 could not be entirely explained by misclassification.