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

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. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.