Venous or arterial thrombosis and deaths among COVID-19 cases: a European network cohort study

Edward Burn, Talita Duarte-Salles, Sergio Fernandez-Bertolin, Carlen Reyes, Kristin Kostka, Antonella Delmestri, Peter Rijnbeek, Katia Verhamme, Daniel Prieto-Alhambra*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: There are few data on the incidence of thrombosis among COVID-19 cases, with most research concentrated on hospitalised patients. We aimed to estimate the incidence of venous thromboembolism, arterial thromboembolism, and death among COVID-19 cases and to assess the impact of these events on the risks of hospitalisation and death. Methods: We conducted a distributed network cohort study using primary care records from the Netherlands, Italy, Spain, and the UK, and outpatient specialist records from Germany. The Spanish database was linked to hospital admissions. Participants were followed up from the date of a diagnosis of COVID-19 or positive RT-PCR test for SARS-CoV-2 (index date) for 90 days. The primary study outcomes were venous thromboembolic events, arterial thromboembolic events, and death, all over the 90 days from the index date. We estimated cumulative incidences for the study outcomes. Multistate models were used to calculate adjusted hazard ratios (HRs) for the association between venous thromboembolism or arterial thromboembolism occurrence and risks of hospitalisation or COVID-19 fatality. Findings: Overall, 909 473 COVID-19 cases and 32 329 patients hospitalised with COVID-19 on or after Sept 1, 2020, were studied. The latest index dates across the databases ranged from Jan 30, 2021, to July 31, 2021. Cumulative 90-day incidence of venous thromboembolism ranged from 0·2% to 0·8% among COVID-19 cases, and up to 4·5% for those hospitalised. For arterial thromboembolism, estimates ranged from 0·1% to 0·8% among COVID-19 cases, increasing to 3·1% among those hospitalised. Case fatality ranged from 1·1% to 2·0% among patients with COVID-19, rising to 14·6% for hospitalised patients. The occurrence of venous thromboembolism in patients with COVID-19 was associated with an increased risk of death (adjusted HRs 4·42 [3·07–6·36] for those not hospitalised and 1·63 [1·39–1·90] for those hospitalised), as was the occurrence of arterial thromboembolism (3·16 [2·65–3·75] and 1·93 [1·57–2·37]). Interpretation: Risks of venous thromboembolism and arterial thromboembolism were up to 1% among COVID-19 cases, and increased with age, among males, and in those who were hospitalised. Their occurrence was associated with excess mortality, underlying the importance of developing effective treatment strategies that reduce their frequency. Funding: European Medicines Agency.

Original languageEnglish
Pages (from-to)1142-1152
Number of pages11
JournalThe Lancet Infectious Diseases
Issue number8
Publication statusPublished - 1 Aug 2022

Bibliographical note

Funding Information:
This study was funded by the European Medicines Agency in the form of a competitive tender (Lot ROC No EMA/2017/09/PE). The views expressed in this Article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its committees or working parties. We acknowledge Prof Johan Van der Lei (Medical Informatics, Erasmus University Medical Centre, Rotterdam, Netherlands) for the overall management of this research grant.

Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.


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