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Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
School of Mathematics and Statistics, The Open University, Milton Keynes, UK.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.ORCID iD: 0000-0002-5328-9536
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2022 (English)In: The BMJ, E-ISSN 1756-1833, Vol. 377, article id e069590Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19.

DESIGN: Self-controlled case series and matched cohort study.

SETTING: National registries in Sweden.

PARTICIPANTS: 1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants.

MAIN OUTCOMES MEASURES: Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event).

RESULTS: Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding.

CONCLUSIONS: The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2022. Vol. 377, article id e069590
National Category
Cardiac and Cardiovascular Systems Surgery
Research subject
Surgery; Surgery
Identifiers
URN: urn:nbn:se:umu:diva-193662DOI: 10.1136/bmj-2021-069590ISI: 000784456300002PubMedID: 35387772Scopus ID: 2-s2.0-85127678172OAI: oai:DiVA.org:umu-193662DiVA, id: diva2:1651075
Available from: 2022-04-11 Created: 2022-04-11 Last updated: 2024-07-02Bibliographically 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
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
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)
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Supervisors
Available from: 2023-09-08 Created: 2023-09-01 Last updated: 2023-09-19Bibliographically approved

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Katsoularis, IoannisFonseca-Rodríguez, OsvaldoJerndal, HannaHäggström Lundevaller, ErlingSund, MalinLindmark, KristerFors Connolly, Anne-Marie

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