Synergistic Effect of SARS-CoV-2 Infection and COVID-19 Vaccination on the Risk of Venous Thromboembolism

Abstract

Background: Previous studies have reported a greater risk of venous thromboembolism among patients infected with SARS-CoV-2 and those who received COVID-19 vaccination. Nevertheless, there is a lack of understanding regarding the interaction effect on the risk of venous thromboembolism occurrence between SARS-CoV-2 infection and COVID-19 vaccination. Methods: This was a retrospective cohort study including adult patients with confirmed SARS-CoV-2 infection between October 2020 and September 2021. Patients with confirmed SARS-CoV-2 infection were selected and matched 1:1 by age and sex with individuals who were not infected during the same period. A Cox proportional hazards model was used to analyze the venous thromboembolism risk. Results: The study included 422546 individuals who were divided into 4 groups; the interaction group defined by having SARS-CoV-2 infection within 90 days following COVID-19 vaccination, the infection group defined by no vaccination before 90 days of SARS-CoV-2 infection, the vaccination group defined by COVID-19 vaccination without SARS-CoV-2 infection, and the reference group defined by neither COVID-19 vaccination nor SARS-CoV-2 infection. The results showed that the adjusted hazard ratio (aHR) of the interaction group was 29.71 (95% confidence interval [CI], 22.95-38.47), while the aHRs of the infection group and the vaccination group were 6.66 (95% CI, 5.18-8.58) and 2.31 (95% CI, 1.78-3.00), respectively. Conclusions: A synergistic effect on the risk of venous thromboembolism was suggested when individuals were infected with SARS-CoV-2 within 90 days following COVID-19 vaccination.