COVID-19 and Smoking

Abstract

COVID-19 is mainly a disease of the respiratory tract characterized by a severe acute respiratory syndrome; the causative agent is SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). The virus main entrance way is through mucosal tissues: nose, mouth, upper respiratory tract, and less frequently conjunctival mucosa. Tobacco smoke exposure results in inflammatory processes in the lung, increased mucosal inflammation, expression of inflammatory cytokines and tumor necrosis factor α, increased permeability in epithelial cells, mucus overproduction, and impaired mucociliary clearance.1 Knowledge about host factors, and in particular avoidable host factors such as smoking, may be of importance in reducing viral contamination and the severity of the disease. The SARS-CoV-2 pandemic started in Wuhan, China toward the end of 2019. To the best of our knowledge and at the time of the writing of this Commentary, six published case series reported the prevalence of smoking among individuals with COVID-19 (Table 1). The study with the highest number of patients compared severe (N = 173) to nonsevere (N = 926) cases. The percent of current and former smokers were higher among the severe cases: 17% and 5%, respectively, than among the nonsevere cases (12% and 1%, respectively).2 More importantly, among those with the primary composite end point (admission to an intensive care unit, the use of mechanical ventilation, or death), the proportion of smokers was higher with than among those without this end point (26% vs. 12%).2 Another case series also showed more smokers among the severe (N = 58) than among the nonsevere (N = 82) cases.3 The single modifiable host factor associated with progression of COVID-19 pneumonia was current smoking in a multivariable logistic analysis (odds ratio = 14.3, 95% confidence interval: 1.6–25.0).4 Among those who died the number of smokers was also been found to be somewhat higher (9%, 5/54) than among survivors (6%, 9/137).5 Frequency of Smoking and Former Smoking Among COVID-19 Patients. N (%) ICU: intensive care unit. Frequency of Smoking and Former Smoking Among COVID-19 Patients. N (%) ICU: intensive care unit. Vardavas and Nikitara’s recent systematic review8 identified five studies2–6 and concluded that “smoking is most likely associated with negative progression and adverse outcomes of COVID-19.” Conversely, Lippi and Henry’s short meta-analysis reported no association of smoking status with severity of COVID-19.9 However, the number of cases in most studies to date is very low, and consequently the 95% confidence intervals very wide. These case series reports are descriptive and do not allow to draw firm conclusions about the association of severity of COVID-19 with smoking status. Underlying health conditions such as COPD, diabetes, and coronary heart disease are more prevalent among severe cases.2,5 Although these can causally be associated with smoking, the specific effect of smoking on COVID-19 severity cannot be disentangled. However, the nicotine and tobacco research and health care community cannot ignore these signals. We know that tobacco smoke exposure is a major risk factor for lung disease1 and cigarette smoking is a substantial risk factor for bacterial and viral infections.10 In addition, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) that caused a small coronavirus epidemic in 2012–215 presented the same clinical features as the current COVID-19, and reports also indicated an association between smoking status and fatality rate,11 with current smoking also more frequent among cases than among controls (37% vs. 19%, odds ratio = 3.14, 95% confidence interval: 1.10–9.24, N = 146).12 MERS-CoV infection involves the dipeptidyl peptidase IV (DPP4) receptor while SARS-CoV-2 involves the ACE2 receptor (angiotensin II conversion enzyme-2 receptor). Both are abundant in mucosal epithelial cells and lung alveolar tissue and have multiple physiological functions. To infect the host, both viruses attach to its receptor: MERS-CoV to DPP4 and SARS-CoV-2 to ACE2, a probably key step for coronavirus infections. DPP4 mRNA and protein expressions are significantly higher in smokers compared with never smokers without airflow limitation and are inversely correlated with lung function.13 It has recently been reported that ACE2 gene expression is higher in ever smokers (both current and former) compared with never smokers in normal lung tissue in a sample of patients with lung adenocarcinoma, after adjustment for age, gender, and ethnicity. ACE2 gene expression was also higher in small and large airway epithelia of healthy ever smokers compared with never smokers: current smokers had the highest expression, never smokers had the lowest expression; recent former smokers (≤15 years) had higher ACE2 gene expression than nonsmokers but not long-term former smokers (>15 years).14 The similar upregulation associated with smoking of two different virus receptors observed with