Researchers Explore Link Between Smoking Status and COVID-19 Outcomes

Strategic Alliance Partnership | <b>Cleveland Clinic</b>

Increased cumulative smoking was associated with increased risk of hospitalization and death.

There is not much proven evidence showing the link between smoking status and adverse outcomes from SARS-CoV-2 infections.

In addition, the evidence that does exist does not encompass the cumulative impact of smoking over time.

A team, led by Katherine E. Lowe, MSc, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, assessed the cumulative effect of smoking over time measured by pack-years through a single study of coronavirus disease 2019 (COVID-19).

In the cohort, the investigators examined patients with lung cancer who tested positive for COVID-19 between March 8 and August 25, 2020 and had full smoking information recorded.

Smoking Status

The investigators identified 7102 patients, 6020 of which were never smokers, 172 were current smokers, and 910 were former smokers.

The researchers used a COVID-19 registry that began at the Cleveland Clinic last March and included all patients tested for COVID-19 within the Cleveland Clinic Health system in Ohio and Florida.

They collected basic demographic information during testing, including age, height, weight, self-reported gender, self-reported race, and selective comorbidities. They also extracted additional data on comorbidities, medications, and outcomes from patient electronic medical records.


The investigators classified patients based on their cumulative recorded smoking exposure, including those who were never smokers compared to patients reporting 0-10 pack-years, 10-30 pack-years, and more than 30 pack-years. Demographic differences between the different groups and previous literature on the risk factors of adverse COVID-19 outcomes informed the overall study modeling.

The investigators also used multivariable logistic regression models to determine the odds ratio (OR) for hospitalization following a positive test, admission to the intensive care unit given hospitalization, and death following a positive test for each pack-year cohort compared to never smokers.

The team also used regression models run unadjusted, adjusted for identified confounders such as 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.

Finally, the researchers used likelihood ratio tests to determine whether a given covariate would remain in the model.


The investigators found a dose-response association between pack-years and adverse COVID-19 outcomes.

The patients who smoked more than 30 pack-years had a 2.25 times higher odds of hospitalization (95% CI, 1.76-2.88). This patient population was 1.89 times more likely to die following a COVID-19 diagnosis (95% CI, 1.29-1.76) when compared with never smokers. The link between cumulative smoking and adverse outcomes is likely mediated in part by the individual’s comorbidities.

The odds ratios for all adverse outcomes were attenuated in the mediation models.

The researchers also did not find evidence of effect modification by smoking status.

“We have demonstrated in this single central registry of patients who tested positive for COVID-19 that increased cumulative smoking was associated with a higher risk of hospitalization and mortality from COVID-19 in a dose-dependent manner,” the authors wrote.

The research letter, “Association of Smoking and Cumulative Pack-Year Exposure With COVID-19 Outcomes in the Cleveland Clinic COVID-19 Registry,” was published online in JAMA Internal Medicine.