Smoking habit and hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- related pneumonia: The unsolved paradox behind the evidence.

While there is preliminary (and apparently logical) evidence of a relationship between smoking and severity of COVID 19, it remains to be clarified: 1) whether the impact of smoking on COVID-19-outcome is rather linked to the smoking-related comorbidities, and 2) which comorbidities are associated with a worse clinical course of SARS-CoV-2 infection. A recent retrospective, multicenter study of 150 confirmed COVID19 cases in Wuhan, China, showed that elevated inflammatory indicators in the blood, including interleukin-6 (IL-6), could be predictors of a fatal outcome in COVID-19, suggesting that mortality might be due to virus-activated ‘cytokine-storm syndrome. The exposure to smoke has been shown to modulate immune and adaptive immune responses and reduce systemic levels of several immune/inflammation markers, when compared with never smokers. Thus, smoking could attenuate the normal defensive function of the immune system, which becomes tolerant of a continuous inflammatory insult, while the immune system of never smokers may be more suitable for a cytokine release syndrome. Paradoxically, a provocative hypothesis could be that the cytokine storm with excessive production of pro inflammatory molecules could possibly more easily be triggered in a perfectly immuno-competent individual rather than in smokers. In this regard, we may assume that the immune system of a current smoker is more tolerant and less reactive, compared to patients who have never smoked, whose immune system may be more suitable for triggering a cytokine release syndrome, that could be associated to COVID-19-related high mortality. This can contribute to partially explain the data observed in the studies published so far, reporting the great majority of COVID −19 hospitalized patients as non-smokers. In addition, it should be considered that the prevalence of smoking in the studies published so far refers only to hospitalized patients, with more severe symptoms of the disease than individuals who not admitted to hospital. The hospitalized patients represent only a (hopefully small) part of the COVID-19 positive population. Indeed, it is likely that the SARS-CoV-2 infection occurs asymptomatically or with mild symptoms that do not require hospitalization; the prevalence of smoking in these cases is unknown and actually it does not help the clarify the association between smoking and severity of pneumonia. Therefore, it is not currently possible to establish the real prevalence of smoking among all individuals affected with COVID-19. However, according to the studies published so far, smokers represent a minority among hospitalized patients. It would be interesting to investigate the spread of smoking among asymptomatic individuals or those with few symptoms, in order to clarify whether smoking is a real risk factor not only for the clinical course but also for contracting and manifesting the infection. To read more-


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