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A Comprehensive Assessment of The Impact of COVID Variant and Vaccination on Venous Thromboembolism and Mortality
Journal article   Open access   Peer reviewed

A Comprehensive Assessment of The Impact of COVID Variant and Vaccination on Venous Thromboembolism and Mortality

Samuel P. Soff, Richard Moffitt, Anjali Sharathkumar, Margaret A. Hall, Rachel Wong, Yun Jae Yoo, Gerald A. Soff and National Clinical Cohort Collaborative (N3C) COVID-19 Enclave
Research and practice in thrombosis and haemostasis, 103415
03/2026
DOI: 10.1016/j.rpth.2026.103415
url
https://doi.org/10.1016/j.rpth.2026.103415View
Published (Version of record) Open Access

Abstract

COVID-19 is associated with increased mortality and morbidity. The mortality and adverse outcomes of current era COVID-19 variants have not been comprehensively studied. To evaluate the association between COVID-19 variants and vaccination status on venous thromboembolism (VTE) and mortality rates, especially among recent strains, compared to a control group with acute respiratory infection (ARI). A retrospective cohort study was conducted using the N3C database. Inclusion criteria were adult patients with COVID-19 or ARI between 3/1/2020-11/1/2024. Cohorts were balanced on demographics, prior healthcare visits, prior anticoagulation/antiplatelet use, COVID-19 vaccination and comorbidities. Primary outcomes were 30-day VTE and mortality using multivariable regression analysis. Kaplan Meier survival curves were used to determine the duration of post-infectious VTE and mortality risk. A total of 756,217 patients with COVID-19 and 678,747 with ARI were included. Patients with COVID-19 had an increased risk of VTE (OR: 1.45) and mortality (OR: 1.80) compared to the ARI cohort. However, risk was attenuated later in the pandemic, with similar risk between patients with COVID-19 and ARI in the Contemporary Omicron period (May 2022-Dec 2024), especially among vaccinated individuals. Vaccination was associated with a reduced odds of VTE (OR: 0.41) and mortality (OR: 0.41). The post-COVID elevated VTE and mortality risk plateaued after 8 weeks. COVID-19 was associated with increased risk of 30-day VTE and mortality compared to ARI, but was no longer significantly different during the contemporary period (2022-2024) of the pandemic. COVID-19 vaccination was associated with reduced VTE events and mortality. 1.COVID-19 is associated with increased mortality and thrombosis2.Using a large national database, we studied COVID-19 30-day mortality and thrombosis3.Current era (2022-2024) COVID-19 was not more severe than acute respiratory infection4.COVID vaccination reduced thrombosis and mortality rates by approximately 60%

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