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

March 5, 2024 updated by: Maria Rosaria Galanti, Karolinska Institutet

The Association Between Tobacco Use and COVID-19 Infection and Adverse Outcomes in Three Nordic Countries: a Pooled Analysis

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.

Study Overview

Status

Completed

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Actual)

757585

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
    • Stockholm
      • Solna, Stockholm, Sweden, 171 77
        • Karolinska Institutet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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 (Galanti, 2021), Finland (Peña et al., 2021), and Norway (Magnus et al., 2016). We will use the national personal number assigned to every resident in these three countries at birth or at immigration to obtain information on diagnoses of COVID-19 and adverse outcomes among individuals in these cohorts through record-linkage with regional and national databases.

Description

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
The Swedish Cohort
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
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Any diagnosis of COVID-19 measured as follows:
Time Frame: February 2020 - December 2020

Sweden: at least a positive polymerase chain reaction test (PCR) reported by the laboratories to Sweden's national electronic surveillance system for communicable diseases (SmiNet).

Finland: cases with a positive SARS-CoV-2 reverse transcription PCR (RT-PCR), either informed by a laboratory or by a physician as a record of an International Classification of Diseases, Tenth Revision (ICD-10) code U07.1 (which requires a positive SARS-CoV-2 RT-PCR).

Norway: a positive test for SARS-CoV-2 based on PCR obtained from The Norwegian Surveillance System for Communicable Diseases (MSIS) or the presence of antibodies for SARS-CoV-2.

Out of these definitions a categorical variable will be created (No recorded COVID-19 diagnosis= 1, registered COVID-19 diagnosis= 2)
February 2020 - December 2020
Hospital admission for COVID-19 measured as follows:
Time Frame: February 2020 - December 2020

Any hospital admission with a diagnosis of COVID-19 (ICD-10 codes U071 and U072). The diagnosis could be registered either as a main or as a concomitant diagnosis.

A. A categorical variable for hospital admission with any diagnosis of COVID-19 (either main or secondary diagnosis) will be created (No admissions= 1, any admission= 2).

B. A categorical variable for hospital admission with COVID-19 as the main diagnosis only (No admissions= 1, any admission= 2).
February 2020 - December 2020
Intensive unit care because of a diagnosis of COVID-19 measures as follows:
Time Frame: February 2020 - December 2020
Admission to an intensive care unit (ICU) because of a diagnosis of COVID-19 (ICD-10 codes as above). A categorical variable for intensive unit care because of a diagnosis of COVID-19 (No/Yes) will be created (No ICU care= 1, any ICU care= 2).
February 2020 - December 2020
Death for COVID-19 measured as follows:
Time Frame: February 2020 - December 2020
Death due to COVID-19 will be established using the Swedish, Finnish, and Norwegian Cause of Death Registries. All deaths occurring during the follow-up period with COVID-19 registered as the main cause will be included.
February 2020 - December 2020

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of hospital stay for COVID-19
Time Frame: February 2020 - December 2020
As a secondary analysis, we will use a negative binomial count model (Hilbe, 2011, 2014) to assess inpatient length of stay measured as the cumulative number of days of hospitalization, as an indicator of disease severity among tobacco users compared to non-tobacco users.
February 2020 - December 2020

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Collaborators

Norwegian Institute of Public Health
Finnish Institute for Health and Welfare

Investigators

  • Principal Investigator: Maria Rosaria Galanti, Department of Global Public Health, Karolinska Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2022

Primary Completion (Actual)

December 31, 2023

Study Completion (Actual)

December 31, 2023

Study Registration Dates

First Submitted

April 8, 2022

First Submitted That Met QC Criteria

April 8, 2022

First Posted (Actual)

April 11, 2022

Study Record Updates

Last Update Posted (Estimated)

March 6, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 105544

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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