Smoking and COVID-19

This is an update to the Scientific Brief entitled ‘Smoking and COVID-19,’ originally published on 26 May 2020. Since its publication, a study entitled ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19’ by Mehra et al. has been retracted by the New England Journal of Medicine. This version of the Scientific Brief has removed the study from the review. The removal of this study from the review does not change the conclusions of the analysis.

What is the risk of severe COVID-19 disease and death amongst smokers?

Meta-analyses:
Zhao et al. 35 analysed data from 7 studies (1726 patients) and found a statistically significant association between smoking and severity of COVID-19 outcomes amongst patients (Odds Ratio (OR) 2.0 (95% CI 1.3 -3.1). The statistical significance disappeared when the largest study by Guan et al. 13 was removed from the analysis (a sensitivity test to see the impact of a single study on the findings of the meta-analysis). An updated version of this meta-analysis which included an additional study remained significant when this same sensitivity test was applied however. 36 Zheng et al. 37 analysed data from 5 studies totalling 1980 patients and found a statistically significant association between smoking and COVID-19 severity when using a fixed effects model: OR: 2.0 (95% CI 1.3 -3.2). Lippi et al. 38 analysed data from 5 studies totalling 1399 patients and found a non-significant association between smoking and severity. Guo et al., 39 however, later identified errors in the calculation and concluded that this association was indeed statistically significant (OR 2.2 (95% CI 1.3 -3.7). Vardavas et al. 40 analysed data from 5 studies totalling 1549 patients and calculated a relative risk that indicated a non-significant relationship between smoking and severity of COVID-19. However, the same authors found a statistically significant association between smoking status and primary endpoints of admission to Intensive Care Unit (ICU), ventilator use or death.

Individual studies not included in meta-analyses:
Nine studies were not included in any of the meta-analyses identified. One of these studies reported observational data for 7162 people in hospital and outpatient settings in the United States of America but did not include any statistical analysis of association. 10 Another study of 323 hospitalized patients in Wuhan, China, reported a statistically significant association between smoking and severity of disease (OR 3.5 (95% CI 1.2 -10.2). 15 Kozak et al. 41 found a statistically significant association between smoking and ICU admission and mortality amongst 226 patients in Toronto, Canada. The remaining six studies were small case series (ranging from 11 to 145 people) that reported no statistically significant associations between smoking status and severity of COVID-1, 8,11,18,27,42 apart from Yu et al. 43 who reported on a study of 70 patients a statistically significant OR of 16.1 (95% CI 1.3 -204.2) in a multivariate analysis examining the association between smoking and the exacerbation of pneumonia after treatment.

Limitations
Hospital based studies that report patient characteristics can suffer from several limitations, including poor data quality. Collecting smoking history is challenging in emergency contexts and severity of disease is often not clearly defined and is inconsistent across studies. Such studies are also prone to significant sampling bias. Characteristics of those who are hospitalized will differ by country and context depending on available resources, access to hospitals, clinical protocols and possibly other factors not considered in the studies. Further, most studies did not make statistical adjustments to account for age and other confounding factors.
Well-designed population-based studies are needed to address questions about the risk of infection by SARS-CoV-2 and the risk of hospitalization with COVID-19.

Conclusions
At the time of this review, the available evidence suggests that smoking is associated with increased severity of disease and death in hospitalized COVID-19 patients. Although likely related to severity, there is no evidence to quantify the risk to smokers of hospitalization with COVID-19 or of infection by SARS-CoV-2 was found in the peer-reviewed literature. Population-based studies are needed to address these questions.

Related WHO Recommendations
Given the well-established harms associated with tobacco use and second-hand smoke exposure; 2 WHO recommends that tobacco users stop using tobacco. Proven interventions to help users quit include toll-free quit lines, mobile text-messaging cessation programmes, nicotine replacement therapies and other approved medications.