The Impact of Smoking Status and Smoking-Related Comorbidities on Coronavirus Disease 2019 Patient Outcomes: A Causal Mediation Analysis

• Published in: Nicotine & tobacco research 2023-01, Vol.25 (2), p.331-338
• Main Authors: Le Guen, Claire L, Muir, Kelsey C, Simons, Melanie, Coffman, Donna L, Soans, Rohit S
• Format: Article
• Language: English
• Subjects: Comorbidity; COVID-19 - epidemiology; Hospitalization; Humans; Mediation Analysis; Retrospective Studies; SARS-CoV-2; Smoking - epidemiology
• ISSN: 1469-994X; 1469-994X
• DOI: 10.1093/ntr/ntac193

Smoking history is a known risk factor for significant chronic diseases as well as pulmonary infections; however, the impact of smoking status on coronavirus disease 2019 (COVID-19) outcomes has not been conclusively characterized. This study aims to evaluate the association of smoking status on COVID-19 outcomes, and to explore the mechanism by which smoking and smoking-related comorbidities relate to COVID-19 outcomes. Patients admitted with SARS-CoV-2 infection from November 2020 through January 2021 were included in this study. Causal mediation models investigating the associations between smoking status and the outcomes of mortality, intensive care unit (ICU) admission, advanced respiratory support, mechanical ventilation, ICU length of stay, and hospital length of stay, through mediation via smoking-related comorbidities, were examined. Active smokers did not experience worse COVID-19 outcomes once hospitalized. Former smokers had a higher odds of mortality (total effect OR 1.59, 95% CI 1.07 to 2.38, p = .01; indirect effect OR 1.45, 95% CI 1.09 to 1.93, p < .001), and advanced respiratory support (total effect OR 1.31, 95% CI 1.04 to 1.67, p = .02; indirect effect OR 1.26, 95% CI 1.03 to 1.54, p = .02), which were mediated by smoking-related comorbidities. While there was a nonsignificant increase in the total effect for mechanical ventilation, smoking-related comorbidities were significant mediators for their increased need (total effect OR 1.40, 95% CI 0.92 to 2.14, p = .13; indirect effect OR 1.47, 95% CI 1.10 to 1.87, p < .001). Although active smokers did not experience worse COVID-19 outcomes compared to never smokers, these results should be interpreted with caution. Compared to never smokers, former smokers had greater odds of mortality, advanced respiratory support, and mechanical ventilation which was significantly mediated through smoking-related comorbidities. Previous studies have linked smoking status with worse COVID-19 outcomes, and have inferred that smoking-related comorbidities may play a role in these findings. This causal mediation analysis provides statistical evidence supporting this hypothesis, clarifying the risk that smoking-related comorbidities impart on COVID-19 outcomes in those with a smoking history.