Venous thrombosis associated with different types of SARS-CoV-2 vaccines in the Netherlands-results of the TERA case-control study

Abstract

Background

The magnitude of the risk of venous thromboembolism (VTE) after SARS-CoV-2 vaccines is debated.

Methods We included patients with a first VTE in 2021 and controls from a sample of Dutch citizens. Participants completed a questionnaire on VTE risk factors and vaccination, with data linked to Statistics Netherlands. Odds ratios (OR) with 95% confidence intervals (95%CI) expressed the relative rate of VTE within 28 days post-vaccination, adjusted for age, sex, BMI, month of index date, and major VTE risk factors (COVID-19, surgery, cancer, and immobilization). Using previously reported age-stratified VTE incidences, we estimated vaccination's net impact by comparing the number of events attributed to vaccination and prevented by vaccine-induced protection against COVID-19-associated VTE. Results We included 779 VTE patients and 5,311 controls. mRNA vaccines were not associated with VTE risk (BNT162b2 [Pfizer- BioNTech] vaccine OR 1.0, 95%CI 0.7-1.3; mRNA-1273 [Moderna] vaccine OR 1.4, 95%CI 0.8-2.4). Vector-based vaccines were associated with VTE risk (AZD1222 [AstraZeneca]: OR 1.5, 95%CI 1.0-2.5; Ad26.COV2.S [Johnson & Johnson]: OR 2.9, 95%CI 0.9-9.2). Excluding participants with major VTE risk factors, risks changed (BNT162b2: OR 1.5, 95%CI 1.1-2.1; mRNA-1273: OR 0.8, 95%CI 0.3-2.3; AZD1222: OR 2.0; 95%CI 1.0-3.9; and Ad26.COV2.S: OR 3.4; 95%CI 0.7-15.5). We estimated that SARS-CoV-2 vaccines contributed to approximately 700 VTEs but prevented approximately 3,700 VTEs. Conclusion SARS-CoV-2 vaccines are associated with VTE, with varying risks between types of vaccines, and by sex and age. On a population level, in the Netherlands in 2021, SARS-CoV-2 vaccination resulted in a net benefit for the number of VTE events.