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Venous or arterial thrombosis and deaths among COVID-19 cases: a European network cohort study - 21/07/22

Doi : 10.1016/S1473-3099(22)00223-7 
Edward Burn, DPhil a, b, Talita Duarte-Salles, PhD a, Sergio Fernandez-Bertolin, MSc a, Carlen Reyes, PhD a, Kristin Kostka, MPH c, d, Antonella Delmestri, PhD b, Peter Rijnbeek, ProfPhD e, Katia Verhamme, PhD e, Daniel Prieto-Alhambra, ProfPhD b, e,
a Fundació Institut Universitari per a la Recerca a l’Atenció Primària de Salut Jordi Gol i Gurina, Barcelona, Spain 
b Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK 
c Real World Solutions, IQVIA, Cambridge, MA, USA 
d The Observational Health Data Sciences and Informatics Center at The Roux Institute, Northeastern University, Portland, ME, USA 
e Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands 

* Correspondence to: Prof Daniel Prieto-Alhambra, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK Centre for Statistics in Medicine Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford Oxford OX3 7LD UK

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Summary

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.

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© 2022  The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 22 - N° 8

P. 1142-1152 - août 2022 Retour au numéro
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