Tobacco smoking and the risk of Long COVID: a prospective cohort study with mediation analysis

Abstract

Background: Tobacco smoking is a well-established risk factor for severe acute COVID-19 outcomes, but evidence regarding its role in Long COVID is limited and inconsistent. This study investigated whether pre-pandemic smoking independently predicted Long COVID and assessed mediation by long-standing illness or disability in a nationally representative cohort. Methods: We analysed data from Waves 10 (2018−19) and 14 (2022−23) of the UK Household Longitudinal Study. Smoking status (current vs non-smoker) and covariates (age, sex, education, income satisfaction, ethnicity, rural/urban residence) were measured at baseline (Wave 10). Long COVID, defined as symptoms lasting ≥12 weeks following initial COVID-19 infection, was assessed at follow-up (Wave 14). Logistic regression was used to estimate the total association between smoking and Long COVID. We then applied generalized structural equation modelling and parametric causal mediation analysis, specifying long-standing illness or disability at baseline as the mediator. Results: Among 11,944 participants, 1097 (9.2 %) reported Long COVID symptoms at follow-up. In the unadjusted model, smoking was associated with increased odds of Long COVID (odds ratio [OR] = 1.22, 95 % CI: 1.00 −1.48, p = 0.05), although this was only borderline significant. After adjusting for demographic and socioeconomic factors, the association was no longer statistically significant (adjusted OR = 1.11, 95 % CI: 0.91−1.35, p =0.32). The structural equation model indicated that smoking was associated with higher likelihood of longstanding illness or disability at baseline (β = 0.461, 95 % CI: 0.33−0.59, p <0.001, log-odds scale), which in turn predicted Long COVID (β = 0.435, 95 % CI: 0.30−0.57, p <0.001, log-odds scale). Mediation analysis revealed a small but statistically significant indirect effect of smoking on Long COVID operating through long-standing illness or disability (risk difference = 0.0057, 95 % CI: 0.0020−0.0095, p = 0.003), but no significant direct effect (risk difference = 0.0027, 95 % CI: −0.0144 to 0.0199, p = 0.76). Conclusion: Smoking did not independently predict Long COVID, but may increase vulnerability indirectly through pre-existing long-standing illness or disability.

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http://creativecommons.org/licenses/by/4.0/

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DOI

http://dx.doi.org/10.1016/j.jeph.2025.203142

Repository URI

https://eprints.gla.ac.uk/369454/