Title : Is cigarette smoking a potential protective factor for COVID-19 infection and its symptoms in community population? —— A nested case-control study and clinical characteristics analysis
Abstract:
Background: Cigarette smoking is an unhealthy lifestyle behavior, which can cause a high incidence of respiratory, cardiovascular, endocrine diseases and even tumor . In the past three-year COVID-19 pandemic, there were many researches on the relationship between cigarette smoking and the morbidity, clinical symptoms, and clinical outcomes of COVID-19. Studies showed that cigarette smoking can exacerbate COVID-19 infection in patients and was a risk factor for prognosis.
However, other some studies found opposite results: smoking was negatively correlated with COVID-19 infection, clinical symptoms, and prognosis, and was a potential protective factor for COVID-19. Therefore, the relationship between cigarette smoking and COVID-19 is highly controversial. Chinese Mainland has comprehensively adjusted the prevention and control strategy of COVID-19 since December 2022. The research showed that from December 2022 to September 14, 2023, more than 82% of the people in China (about 1.1 billion to 1.2 billion people) may be infected with COVID-19 virus, which provided a large number of samples for community population research. Therefore, this study aimed to further explore the relationship between cigarette smoking and the morbidity, clinical symptoms, and clinical outcomes of COVID-19 in the community population using nested case control study and clinical characteristics analysis.
Methods: In this study, a community cohort population was selected, which has never infected with COVID-19 before December 1, 2022. Nested case-control study design and COVID-19 nucleic acid detection was carried out, we selected 8796 newly diagnosed patients with COVID-19 infection who were followed up to April 2023 as the case group, and 1551 residents who were not infected with COVID-19 in the same street as matched conditions were the control group. The general demographic, smoking and other life behaviors, basic disease history, COVID-19 infection related symptoms, the course of disease among the subjects were collected with a questionnaire.
The Ethics Committee of Pingshan hospital, Southern Medical University approved this study, and participants provided electronic informed consent. t-test, chi square test, and conditional logistic regression model were used to analyze the dose-response relationship between cigarette smoking exposure and COVID-19 infection, clinical symptoms, and duration of disease. Analysis were conducted using SPSS, version 25.0 Two sided P<0.05 was considered significant
Result: Of 8796 COVID-19 cases enrolled in this study were included 5063 (57.6%) male and 3733 (42.4) female, mean [SD] age, 33.36 [9.24] years. While the 1551 control residents were included 1088 (70.1%) male and 463 (29.95) female, mean [SD] age, 33.47 [10.47] years. The case group patients’ BMI was 22.71 ± 3.47, the control group patients’ BMI was22.73 ± 3.61, There was no statistical difference between the two groups in the prevalence of chronic lung diseases, hypertension, diabetes, coronary heart disease, stroke, kidney disease, tumor and other chronic diseases (P>0.05). (Shown at Supplementary Table1), which was comparable. In the case group, the proportions of never smoking, former smoking, and current smoking were 76.2%, 4.7%, and 19.2%, while the proportions of those in control group were 59.7%, 5.1%, and 35.8%, respectively.
The current smoking rate in the case group was significantly lower than that in the control group, with an OR value of 0.536 (P<0.001). The OR values of current smoking for COVID-19 infection in 18-20,20-30,30-40,40-50,50-60, ≥60 years old groups were 0.708, 0.517, 0.501, 0,646,0.602, and 0.741, respectively. For objects without chronic diseases, the OR values of smoking for COVID-19 infection were 0.703 , while those with one or more chronic diseases were not associated between smoking with COVID-19 infection(Table 1).
Further analysis of the relationship between smoking and clinical symptoms and duration of disease in the case group showed that the proportion of 8796 COVID-19 patients with high fever above 39.0 ?, fever ≥ 4 days, recurrent fever, weight loss ≥ 3Kg and duration of disease more than one week was 34.4%, 12.4%, 39.0%, 1.8% and 27.3%, respectively. The patients suffered from 4.54 ± 2.83 symptoms related to COVID-19 infection. The incidence of high fever above 39.0 ?, fever ≥ 4 days, recurrent fever, and duration of disease more than one week showed a dose-response pattern with smoking: never smokers>those with less than 10 cigarettes per day/d> those with 10-20 cigarettes per day/d> those with 20-40 cigarettes per day/d.
The OR values of smoking for the above four symptoms in COVID-19 infected patients are 0.706, 0.574, 0.559, and 0.413, respectively. However, the proportion of patients in the group who currently smoked more than 40 cigarettes per day showed an increase in fever for ≥ 4 days, recurrent fever, weight loss of ≥ 3KG, and duration of disease more than one week (Table 2).
Discussion: This study showed that the current smoking rate of the COVID-19 infection case group was significantly lower than that of control group, and there was a low risk of smoking for COVID-19 infection in people of all ages from 20 to 60, but this phenomenon only appears in people without chronic diseases, and there is no correlation above in patients with chronic diseases. At the same time, we analyzed the relationship between smoking and clinical symptoms and duration of disease in patients with COVID-19 infection, and found that the main symptoms and duration of COVID-19 infection, such as high fever above 39.0 ?, fever ≥ 4 days, recurrent fever and the duration of disease more than one week, had a negative dose-response with smoking, that is, within a certain amount of smoking, which is a low risk factor for the symptoms and duration of of COVID-19.
The unhealthy effects of cigarette smoking are well known and have not to be questioned [6]. However, many studies have found that cigarette smoking was a protective factor for hospitalization and prognosis in COVID-19 infected patients [7,8], Previous researches showed that the mechanism may be that nicotine in tobacco acted through the AEC2 receptor [9,10]. It is still debased a possible “protective” effect of active cigarette smoking on the risk of COVID-19 and in specific for interactive lung pneumonia due to SARS-CoV-2 infection.
Unlike other studies, this study selected newly infected community populations in China after the implementation of new epidemic prevention and control policies as the research subjects, and found that at a certain dose, current smoking may be the potential protective factor for COVID-19 infection and clinical symptoms in the community population. However, the conclusions of this study need further validation and to investigate the possible mechanisms. This study is not to advocate for cigarette smoking its well known unhealthy behavior, but to provide clinical data and new ideas for future in-depth research on COVID-19 prevention and control and its mechanisms.
