On December 7, 2022, China switched from dynamic zeroing strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to reopening. A nationwide SARS-CoV-2 epidemic emerged rapidly. The effect of smoking on SARS-CoV-2 infection remains unclear. We aimed to retrospectively investigate the relationship between smoking and coronavirus disease 2019 (COVID-19) using a community-based cohort of smokers and non-smokers. We included participants from a pre-pandemic cohort with a prolonged follow-up period. Data on smoking status, body mass index, and history of other diseases were collected from health examination and consultation clinic records. Cox regression analysis was used to identify the relationship between groups and SARS-CoV-2 infection over time. We analysed 218 male patients with varied smoking statuses (46.3% current or ex-smokers; average age 68.63 ± 9.81 years). Two peaks in the epidemic were observed following the December 2022 outbreak. At the end of the second peak, non-smokers, current smokers, and ex-smokers had primary infection rates increase to 88.0%, 65.1%, and 81.0%, respectively, with a significant difference between the groups. Current smoking significantly protected against SARS-CoV-2 infection (HR 0.625, 95% CI 0.402–0.970, p = 0.036). Further analyses showed that the prevalence of pneumonia in the unvaccinated, older, diabetic, and non-smoking groups was significantly higher than that in the other groups (p < 0.05). Our study suggests a potential association between smoking and a reduced risk of SARS-CoV-2 infection and pneumonia. This indicates that nicotine and ACE2 play important roles in preventing COVID-19 and its progression. We suggest smokers use nicotine replacement therapy during hospitalization for COVID-19.
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