RISK OF THROMBOEMBOLISM AFTER COVID-19 VACCINATION AND COVID-19 INFECTION.

Background: Vaccine safety monitoring systems worldwide have reported cases of venous thromboembolism and arterial thromboembolism following a COVID-19 vaccination. However, evidence shows that the association between thromboembolism and SARS-CoV-2 infection is stronger, compared to SARS-CoV-2 vaccination. Hence, weighing the risks and benefits of vaccination should also encounter the roles of vaccination in reducing infection rate, and potentially indirectly lowering the risk of thromboembolism caused by infection. Methods: We conducted a self-controlled case series study (SCCS) from Dec 1st 2020 to 31st August 2022 (before the bivalent vaccine was available) to examinate the association between the first two doses Pfizer/Moderna vaccination and thrombotic events among patients in Corewell Health East (CHE, formerly known as Beaumont Health) healthcare system. We also investigated the effect SARS-CoV-2 infection on the risk of thrombosis events and observed a significant increased risk using the SCCS design. However, because of misclassification bias, SCCS indeed overestimated incidence rate ratio (IRR) of acute event after infection, we then proposed a case-control study addressing this misclassification issues and obtained odd ratio comparing effect of exposure on thrombosis and a subset of controls group. Finally, we analyzed the risk of thromboembolism between vaccinated and unvaccinated groups by a simple diagram, explaining possible factors that affects the probability of experiencing an acute thromboembolism event after a COVID-19 vaccination. Results: Using EHR data at Corewell East, we found an increased risk of thrombosis after the first two doses of COVID-19 vaccination, with incidence rate ratios after the first dose is 1.16 (CI: [1.04, 1.29]), and after the second dose of 1.19 (CI: [1.07,1.32]). The association between thromboembolism and SARS-Cov-2 infection depends on prior vaccination status, as the conditional OR among unvaccinated and vaccinated groups are 1.77 (CI: [1.48,\ 2.1]) and 1.34 (CI: [1.09,\ 1.66]) respectively. Encountering the vaccine efficacy (VE), receiving the COVID-19 vaccine decreases the risk of thromboembolism, and the benefits of COVID-19 vaccines are much stronger in the period of high infection rate.