Tobacco Use and the Risk of COVID-19 and Adverse Outcomes

Karolinska Institute

Status: Completed

Conditions: COVID-19; SARS-CoV-2 Infection; Pneumonia, Viral; Pneumonia; Infections; Virus Diseases; Respiratory Tract Infections

Study type: Observational

Funder types: Other

Identifiers

NCT05321433

105544

Details and patient eligibility

About

This is an observational study of pooled population-based samples in three Nordic countries. Country-specific data has already been analysed in previous studies in Sweden, Finland, and Norway. The primary objective is to examine the association between tobacco use, the risk of SARS-CoV-2 infection, and adverse Outcomes using pooled population-based samples.

Full description

The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 470 million confirmed cases of COVID-19, and more than 6 million deaths around the world by March 25, 2022 (WHO, 2022). Since the beginning of the COVID-19 pandemic, several factors have been attributed to increasing the risk of infection and adverse outcomes of the COVID-19 disease. Among these factors, the relationship between tobacco use and COVID-19 infection and adverse disease outcomes remained controversial as studies kept reporting mixed findings. Early studies reported what seemed to be a protective effect of tobacco use on COVID-19 infection (Haddad et al.; Jiménez-Ruiz et al., 2020), or hospitalizations due to COVID-19 (Farsalinos et al., 2020; Neira et al., 2021). A more recent ongoing living rapid review, this time including a larger selection of studies with different study designs, found that smokers are at reduced risk of SARS-COVID-19 infection compared to non-smokers (Relative risk 0.67, 95% Credible interval 0.60-0.75) (Simons et al., 2021). These findings opened the way for speculations and hypotheses on the potential mechanisms behind this protective role. However, results from most of these studies may be affected by selection bias as they reported findings from clinical samples or bias due to confounding as the structure of these published data permitted only univariate analysis.

Results from studies that suffer from selection bias or bias due to confounding should be handled with caution as they may undermine years of public health education against tobacco use, a major cause of morbidity and mortality worldwide. Moreover, the role of tobacco use in disease progression such as disease requiring hospitalization, ICU, and death remains unclear as most of the previous studies focused more on the association between tobacco use and the risk of infection, but not the adverse outcomes. These facts call for studies that ensure addressing any knowledge gap on the relation between tobacco and COVID-19 by taking into consideration 1) decreasing the risk for confounding and selection bias; 2) increasing precision through a higher sample size, 3) further investigating the association between tobacco use and adverse disease outcomes. In most Nordic countries, the profile of tobacco use in the underlying populations allows the analysis of several types of tobacco use e.g. cigarette smoking and smokeless tobacco (snus) use, enabling further insights into the potential role of nicotine in the association between tobacco use and COVID-19. The use of smokeless tobacco is highly prevalent (even exceeding the prevalence of smoking among men in Sweden and Norway), which will allow us to disentangle a potential role of nicotine in the association between tobacco use and COVID-19.

The investigators propose to examine the associations between tobacco use, COVID-19 infection, and adverse disease outcomes by using pooled population-based data from three Nordic countries, adjusting for potential confounders. The population-based nature of the samples minimizes selection bias Using a pooled analysis will accrue a large sample size and increase the potential for well-powered sub-groups analyses.

Enrollment: 757,585 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Exclusion Criteria:

• All subjects who died before the onset of the pandemic (February 2020) in the three countries will be excluded from the analysis.

Trial design

757,585 participants in 3 patient groups

The Swedish Cohort

Description:

Swedish data comes from a historical cohort of 424,386 clients of public dental clinics aged 23 and older in the Stockholm region with inception between October 2015 and January 2020, with follow-up from February 2020 to December 2020. In Sweden, the public dental clinics (Folktandvården, FTV) provide routine preventive visits (oral check-ups) to all residents who choose to receive care in these clinics. At each health check-up smoking and snus use are ascertained as past use, current use, and amount of current use. The national personal numbers assigned to every resident in Sweden at birth or at immigration will be used to obtain information on diagnoses of COVID-19 and of other diseases through record-linkage with regional health care registers. Demographic information will be extracted through record-linkage with the register of the total population of the Stockholm region held by Statistics Sweden.

The Finnish Cohort

Description:

The Finnish data will come from three pooled cross-sectional national health surveys in Finland (FinSote 2018-2020) of 44,199 participants aged 20 and older. The study samples included permanent residents in Finland from the FinSote surveys 2018, 2019, and 2020. The unique personal identifier assigned to all Finnish residents will be linked to the Communicable Diseases Registry to obtain information on diagnoses of COVID-19, to the Care Register for Health Care (HILMO) to obtain information on hospital admissions due to COVID-19, and to Statistics Finland Mortality Data to obtain information on deaths. Data on some sociodemographic characteristics will be also obtained from the Digital and Population Data Services Agency.

The Norwegian Cohort

Description:

The Norwegian data will be based on the Norwegian Mother, Father and Child Cohort Study (MoBa) (Magnus et al., 2016), and the Norwegian Influenza Pregnancy Cohort (NorFlu) (Laake, 2018), with linkages to the Norwegian Surveillance System for Communicable Diseases (MSIS), the Norwegian Immunisation Registry (SYSVAK), and the Norwegian Population Registry. MoBa is a nation-wide population-based cohort consisting of 280 000 participants, where parents were recruited during pregnancy from 1999 to 2008, while NorFlu is a pregnancy cohort consisting of 9 000 participants recruited in Oslo and Bergen during the swine flu pandemic in 2009-2010. Demographic information is extracted from the registries via linkage to the existing cohort databases. For the purpose of this study, all subjects who died before the onset of the pandemic (February 2020) in the three countries will be excluded from the analysis.