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Avoiding bias in self-controlled case series studies of coronavirus disease 2019
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.ORCID iD: 0000-0002-0253-5928
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.ORCID iD: 0000-0001-9215-4047
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.ORCID iD: 0000-0002-5756-7791
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2021 (English)In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 40, no 27, p. 6197-6208Article in journal (Refereed) Published
Abstract [en]

Many studies, including self-controlled case series (SCCS) studies, are being undertaken to quantify the risks of complications following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). One such SCCS study, based on all COVID-19 cases arising in Sweden over an 8-month period, has shown that SARS-CoV-2 infection increases the risks of AMI and ischemic stroke. Some features of SARS-CoV-2 infection and COVID-19, present in this study and likely in others, complicate the analysis and may introduce bias. In the present paper we describe these features, and explore the biases they may generate. Motivated by data-based simulations, we propose methods to reduce or remove these biases.

Place, publisher, year, edition, pages
John Wiley & Sons, 2021. Vol. 40, no 27, p. 6197-6208
Keywords [en]
bias, cardiovascular disease, COVID-19, epidemiological methods, mortality, self-controlled case series
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:umu:diva-187393DOI: 10.1002/sim.9179ISI: 000691970600001PubMedID: 34470078Scopus ID: 2-s2.0-85114030870OAI: oai:DiVA.org:umu-187393DiVA, id: diva2:1593808
Available from: 2021-09-14 Created: 2021-09-14 Last updated: 2026-05-29Bibliographically approved
In thesis
1. Cardiovascular complications following covid-19: population-based register studies
Open this publication in new window or tab >>Cardiovascular complications following covid-19: population-based register studies
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Kardiovaskulära komplikationer efter COVID-19 : populations-baserade registerstudier
Abstract [en]

Background and Aim: COVID-19 is a multiorgan disease and there has been increasing reports of cardiovascular complications. However, previous studies have shown conflicting results and have mainly included hospitalized individuals with severe disease. The aim of this thesis was to estimate the risk of incident cardiovascular disease following COVID-19. 

Material and Methods: This project was based on Swedish national register data from all individuals who tested positive for SARS-CoV-2 between February 1st, 2020, and May 25th, 2021. Outcomes were events of incident cardiovascular disease, recorded as ICD-10 codes in the National Patient Register. Self-controlled case series (SCCS) studies and matched cohort studies were performed to determine the relative risks for a new onset cardiovascular event following COVID-19. Moreover, a data-simulation study was performed to investigate features that could introduce bias in the SCCS studies: the "day zero-effect", i.e., a high incidence of events at the COVID-19 date; and the increase in mortality due to cardiovascular events.

Results: In the SCCS studies, the risk of cardiovascular disease was significantly increased compared to the control period as follows: up to 14 days after COVID-19 for acute myocardial infarction; up to 1 month for ischemic stroke; up to 3 months for deep vein thrombosis; up to 6 months for pulmonary embolism; up to 2 months for bleeding and for atrial tachycardias; up to 6 months for paroxysmal supraventricular tachycardias; and up to 14 days for bradyarrhythmias. In the matched cohort studies, COVID-19 was associated with an approximately 3- and 4-fold increase in the risk of acute myocardial infarction and ischemic stroke, respectively, during day 1-14 after the infection. During day 1-30 following the infection, the increase in risk was 5-fold for deep vein thrombosis; 33-fold for pulmonary embolism; 2-fold for bleeding; 12-fold for atrial tachycardias; 5-fold for paroxysmal supraventricular tachycardias; and 3-fold for bradyarrhythmias. The relative risks were higher in older individuals with comorbidities, with more severe COVID-19, and during the first months of the pandemic. Unvaccinated individuals had a higher risk of arrhythmias. In the data-simulation study, bias was introduced by including "day-zero events" in the analyses. Moreover, the extended rather the traditional SCCS model was more appropriate to minimize possible bias introduced by the increase in mortality due to cardiovascular events.

Conclusion: There is an increased risk of cardiovascular complications in individuals with COVID-19, especially in individuals with severe disease. These findings highlight the value of diagnostic and prophylactic strategies in individuals with COVID-19, such as risk factor control or thromboprophylaxis, and the value of vaccination. 

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2023. p. 107
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2228
Keywords
COVID-19, SARS-COV-2, cardiovascular disease, nationwide, register, matched cohort study, self-controlled case series study
National Category
Cardiology and Cardiovascular Disease Public Health, Global Health and Social Medicine
Research subject
cardiovascular disease; Epidemiology; Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-213958 (URN)9789180700047 (ISBN)9789180700030 (ISBN)
Public defence
2023-09-29, Hörsal E04, byggnad 6E, målpunkt R-1, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2023-09-08 Created: 2023-09-01 Last updated: 2025-02-20Bibliographically approved

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Fonseca Rodriguez, OsvaldoConnolly-Andersen, Anne-MarieKatsoularis, IoannisLindmark, Krister

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