Introduction Preliminary reports indicated that smokers could be less susceptible to coronavirus SARS-CoV-2, which causes Covid-19. However, once infected an increased risk of severe disease is reported. We investigated the association between smoking and COVID-19 during an outbreak of the disease on a naval vessel. Methods We conducted a cross-sectional, observational study on the 1769 sailors of the same navy aircraft carrier at sea exposed at the same time to SARS-CoV2 to investigate the link between tobacco consumption and Covid-19. Results Among the 1688 crewmembers (87% men; median age = 28 [interquartile range 23–35]) included, 1279 (76%) developed Covid-19 (1038 [62%] reverse-transcriptase- polymerase chain reaction testing–positive and 241 [14%] with only clinical signs). One hundred and seven patients were hospitalized. The univariable analysis odds ratio (OR) for Covid-19 infection was 0.59 (95% confidence interval [CI], 0.45–0.78; p < .001) for current smokers versus former and nonsmokers; sex, body mass index or blood group had no significant impact. Crewmembers >50 years old had an increased risk of contracting Covid-19 (OR, 2.84 [95% CI, 1.30–7.5]; p = .01). Multivariable analysis retained the lower risk of current smokers becoming infected (OR, 0.64 [0.49–0.84]; p < .001) and age >50 years was significatively associated with Covid-19 (OR, 2.6 [1.17–6.9]; p = .03). Conclusions Current smoking status was associated with a lower risk of developing Covid-19 but cannot be considered as efficient protection against infection. The mechanism of the lower susceptibility of smokers to SARS-CoV-2 requires further research. Trial Registration IRB no.: 0011873-2020-09 Implications (1) Recent epidemiologic data suggest a paradoxical link between smoking and COVID-19. (2) Among the 1688 crewmembers (with an attack rate of 76% and exposed at the same time in the same place to SARS-CoV2), we found a significantly lower risk for developing COVID-19 in current smokers (71%) versus former and nonsmokers (80%). This finding strongly supports the need for further research on nicotine physiological pathway and its impact on COVID-19 infection whilst emphasizing that tobacco smoking should not be considered as efficient protection against COVID-19.

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