Here we evaluated the clinical signs and symptoms, laboratory data, imaging findings and outcomes of COVID-19 patients, and compared the smokers with non-smoker patients. Because it has been shown that age and gender significantly affect the clinical picture and outcome of COVID-19 patients (13, 18), we used an age and sex matched control group to eliminate the effect of age and sex in the comparison. Moreover, the prevalence of different comorbidities were not significantly different between smokers and non-smokers. Therefore, any differences in clinical picture or outcome of COVID-19 in our study, cannot be attributed to differences in comorbidities between smokers and non-smokers. Regarding the signs and symptoms of COVID-19, our data demonstrated that smokers are more likely to exhibit chest pain and weakness compared to non-smoker patients. In addition, the number of white blood cells and neutrophils were significantly lower in smokers. However, concerning the clinical outcome of COVID-19 patients, such as days of hospital stay, rate of discharge, readmission and death, our data indicated that no significant difference exists between smokers and non-smokers.
Since the start of SARS-CoV-2 epidemic, several studies have been carried out to identify the role of smoking in clinical picture and disease outcome, however the obtained results are contradictory. Apart from various editorials that have emphasized on the detrimental effects of smoking on COVID-19 patients and severity of the disease (19, 20), many original articles and meta-analyses also indicated that smoker patients have a poorer prognosis compared to non-smokers (11, 13–15, 21). Liu et al, evaluated 78 patients with COVID-19 and reported that patients with progressive disease were more likely to be smokers compared to patients who had improvement/stabilization (13). Moreover, they showed that patients with a history of smoking are roughly 14 times more likely to develop progressive disease. Two systematic reviews also demonstrated that smoking is a risk factor for more severe disease in COVID-19 patients (14, 15). The main principle proposed for this increase in disease severity among smokers, is that smoking results in augmented expression of ACE-2 receptors in lung tissues, and as shown previously, SARS-CoV-2 exploits ACE-2 receptors to enter the pneumocytes and proliferate in them (20, 21). Thus, smokers may be more susceptible to corona virus and experience more severe disease. Another plausible explanation is that smoking causes several diseases such as COPD and cardiovascular disease, which puts smokers at a higher risk compared to non-smokers (19). Accordingly, we excluded smoker patients with other comorbidities from our study and demonstrated that smokers do not differ from non-smokers in case of disease outcomes.
On the other hand, several authors suggested that smoking may not be as harmful as thought. A systematic review conducted by Rubio et al. demonstrated that the proportion of smokers among COVID-19 patients is significantly lower than the percentage of smokers among general population in three different countries including China, Italy and the USA. Thus, they postulated that smokers are significantly less likely to develop severe disease and be hospitalized (16). The proposed mechanism is that nicotine can alleviate the ongoing inflammatory responses and cytokine storm in COVID-19 patients through the cholinergic anti-inflammatory pathway. Forsalinos et al. also showed the same pattern of smoking in COVID-19 patients and general population in China. They hypothesized that COVID-19 symptoms result from a dysfunction of nicotinic cholinergic system and nicotine may be beneficial for patients as it can inhibit pro-inflammatory cytokines, while, not affecting the anti-inflammatory cytokines, through the α7 nicotinic acetyl choline receptors (α7-nAChRs). Ultimately, they suggested evaluating nicotine as an adjunct therapy for COVID-19 patients in clinical trials (6, 17).
Our results are in line with two systematic reviews that showed smoking does not significantly affect the outcome of COVID-19 patients (18, 22). This can be explained by the complex interplay of smoking and coronavirus. Although smoking may enhance the expression of ACE-2 receptors and expose patients to harmful chemical and make them susceptible to various diseases, its nicotine content may inhibit inflammatory responses thus neutralizing the detrimental effects of smoking for COVID-19 patients. Nevertheless we found some differences between smoker and non-smoker COVID-19 patients, including higher prevalence of weakness and chest pain and lower number of white blood cells and neutrophils in smokers. However, these differences are not clinically significant and does not change the clinical course or treatment options.
Our study had several limitations, for instance we did not evaluate other clinical outcomes such as the need for ICU admission or mechanical ventilation. Moreover, some patients’ data were missing especially CT scan findings of 45 patients were not available. However, having an age and sex matched control group with similar comorbidities compared to smoker COVID-19 patients is the strength of our study.