Is there a smoker’s paradox in COVID-19?

Abstract

Although it is well established that cigarette smoking is associated with morbidity and mortality in several respiratory infections, data from recent studies suggest that active smokers are underrepresented among patients with COVID-19. This has led to claims that a ‘smoker’s paradox’ may exist in COVID-19, wherein smokers are protected from infection and severe complications of COVID-19. We aimed to review and summarise existing literature in this context. Electronic databases were searched for articles that reported prevalence of smokers among patients with COVID-19 or studied any association of smoking with outcomes among patients with COVID-19. We identified several biases and knowledge gaps which may give the false impression that smoking is protective in COVID-19. As of now, the data supporting smoker’s paradox claims are limited and questionable. Plausible biologic mechanisms by which smoking might be protective in COVID-19 include an anti-inflammatory effect of nicotine, a blunted immune response in smokers (reducing the risk of a cytokine storm in COVID-19) and increased nitric oxide in the respiratory tract (which may inhibit replication of SARS-CoV-2 and its entry into cells). On the other hand, smoking may worsen susceptibility and prognosis in COVID-19, in a manner similar to other respiratory infections. The claims of a protective effect must be viewed with extreme caution by both the general population as well as clinicians. Further investigations into the interaction between smoking and COVID-19 are warranted to accurately assess the risk of contracting COVID-19 among smokers, and progression to mechanical ventilation or death in patients suffering from it.

Why COVID-19 Transmission Is More Efficient and Aggressive Than Viral Transmission in Previous Coronavirus Epidemics?

“…This is in line with the well-known general correlation between smoking and increased prevalence and mortality of infectious diseases [291], and with the fact that many COPD patients are smokers [285]. One should keep in mind, though, that existing data on the prevalence of smokers among COVID-19 patients and on the association between the COVID-19 outcomes and smoking are rather contradictory [290]. In fact, although some studies showed that smokers are more susceptible to COVID-19, and smoking is associated with more severe disease outcomes [293], several other studies pointed out the underrepresentation of active smokers among the COVID-19 patients [290] and indicated that active smoking is not associated with the COVID-19 severity [294].…”

“…Among different factors potentially affecting the susceptibility to SARS-CoV-2 and changing the outcomes and mortality amongst COVID-19 patients are smoking and vaping [285,[290][291][292]. This is in line with the well-known general correlation between smoking and increased prevalence and mortality of infectious diseases [291], and with the fact that many COPD patients are smokers [285].…”

“…One should keep in mind, though, that existing data on the prevalence of smokers among COVID-19 patients and on the association between the COVID-19 outcomes and smoking are rather contradictory [290]. In fact, although some studies showed that smokers are more susceptible to COVID-19, and smoking is associated with more severe disease outcomes [293], several other studies pointed out the underrepresentation of active smokers among the COVID-19 patients [290] and indicated that active smoking is not associated with the COVID-19 severity [294]. Since these observations of smokers being protected from infection and severe complications of COVID-19 contradict the known association between morbidity and mortality of respiratory infections and cigarette smoking, the existence of a 'smoker's paradox' in COVID-19 was proposed [290].…”

“…In fact, although some studies showed that smokers are more susceptible to COVID-19, and smoking is associated with more severe disease outcomes [293], several other studies pointed out the underrepresentation of active smokers among the COVID-19 patients [290] and indicated that active smoking is not associated with the COVID-19 severity [294]. Since these observations of smokers being protected from infection and severe complications of COVID-19 contradict the known association between morbidity and mortality of respiratory infections and cigarette smoking, the existence of a 'smoker's paradox' in COVID-19 was proposed [290]. Among the possible molecular mechanisms of such protection are inhibition of SARS-CoV-2 entry into cells and replication caused by the smoking-induced increase in the nitric oxide levels in the respiratory tract, anti-inflammatory effects of nicotine, and reduced risk of a cytokine storm in COVID-19 associated with the dampened immune response in smokers [290].…”

“…Since these observations of smokers being protected from infection and severe complications of COVID-19 contradict the known association between morbidity and mortality of respiratory infections and cigarette smoking, the existence of a 'smoker's paradox' in COVID-19 was proposed [290]. Among the possible molecular mechanisms of such protection are inhibition of SARS-CoV-2 entry into cells and replication caused by the smoking-induced increase in the nitric oxide levels in the respiratory tract, anti-inflammatory effects of nicotine, and reduced risk of a cytokine storm in COVID-19 associated with the dampened immune response in smokers [290]. However, systematic analysis of the existing literature pointed out that many results used in support of the smoker's paradox-related claims are questionable and limited, indicating that extreme caution should be used while considering the protective effects of active smoking against COVID-19 [290].…”