The results of a study by Lowe, et al. (2021) suggest that cumulative exposure to cigarette smoke is an independent risk factor for hospital admission and death from COVID-19.

As the researchers explain, "There is limited and contradictory evidence on the association of smoking status with adverse outcomes of severe acute respiratory syndrome coronavirus 2 infection. Furthermore, current smoking status does not encompass the cumulative effect of smoking. To our knowledge, no studies have assessed the cumulative effect of smoking over time, as measured by pack-years, though a single study of coronavirus disease 2019 (COVID-19) in a small cohort of 102 patients with lung cancer found that the patients with severe outcomes had a higher average pack-year history (30 vs 20 years)."

The researchers hypothesize that there is an adverse association of cumulative smoking exposure, as measured by pack-years, with outcomes of patients with COVID-19.

The Cleveland Clinic initiated a COVID-19 registry starting on March 8, 2020, that includes all patients tested for COVID-19 within the Cleveland Clinic Health system in Ohio and Florida. Basic demographic information was collected during testing, including age, height, weight, self-reported gender, self-reported race, and select comorbidities. Additional data on comorbidities, medications, and outcomes were extracted from patient electronic medical records. The Cleveland Clinic Institutional Review Board approved this study and waived the need for patient informed consent owing to use of deidentified database information on study participants.

Adults who tested positive for COVID-19 between March 8, 2020, and August 25, 2020, and who had full smoking information recorded were included in the cohort. The researchers classified patients based on their cumulative recorded smoking exposure. Those who reported that they were never smokers were compared with patients reporting 0 to 10 pack-years, 10 to 30 pack-years, and more than 30 pack-years. Demographic differences between these groups and previous literature on the risk factors of adverse COVID-19 outcomes informed the study modeling. The researchers used multivariable logistic regression models to determine the odds ratio for hospitalization given a positive test, admission to the intensive care unit given hospitalization, and death given a positive COVID-19 test for each pack-year cohort compared with never smokers. Regression models were run unadjusted, adjusted for identified confounders (age, race, and gender) and adjusted for mediators (adding coronary artery disease, hypertension, chronic obstructive pulmonary disease, diabetes, use of angiotensin receptor blockers, and use of oral or inhaled corticosteroids). They used likelihood ratio tests to determine whether a given covariate would remain in the model.

Of the 7102 patients included in the cohort, 6020 (84.8%) were never smokers, 172 (2.4%) were current smokers, and 910 (12.8%) were former smokers. The findings showed a dose-response association between pack-years and adverse COVID-19 outcomes. Patients who smoked more than 30 pack-years had a 2.25 times higher odds of hospitalization (95% CI, 1.76-2.88), and these heavy smokers were 1.89 times more likely to die following a COVID-19 diagnosis (95% CI, 1.29-1.76) when compared with never smokers. The association between cumulative smoking and adverse COVID-19 outcomes is likely mediated in part by comorbidities. The odds ratios for all adverse outcomes were attenuated in the mediation models. There was no evidence of effect modification by smoking status; similar odds ratios were seen in both current and former smokers.

Reference: Lowe KE, et al. Association of Smoking and Cumulative Pack-Year Exposure With COVID-19 Outcomes in the Cleveland Clinic COVID-19 Registry. JAMA Intern Med. Published online January 25, 2021. doi:10.1001/jamainternmed.2020.8360