Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: whole population cohort study in 46 million adults in England

ABSTRACT Background Thromboses in unusual locations after the COVID-19 vaccine ChAdOx1-S have been reported. Better understanding of population-level thrombotic risks after COVID-19 vaccination is needed. Methods We analysed linked electronic health records from adults living in England, from 8 th December 2020 to 18 th March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous and thrombocytopenic outcomes 1-28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years, and adjusted for age, sex, comorbidities, and social and demographic factors. Results Of 46,162,942 adults, 21,193,814 (46%) had their first vaccination during follow-up. Adjusted HRs 1-28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 respectively, were 0.97 (95% CI: 0.90-1.05) and 0.58 (0.53–0.63) for venous thromboses, and 0.90 (0.86-0.95) and 0.76 (0.73-0.79) for arterial thromboses. Corresponding HRs for BNT162b2 were 0.81 (0.74–0.88) and 0.57 (0.53–0.62) for venous thromboses, and 0.94 (0.90-0.99) and 0.72 (0.70-0.75) for arterial thromboses. HRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and thrombocytopenia in adults aged <70 years were higher 1-28 days after ChAdOx1-S (adjusted HRs 2.27, 95% CI:1.33– 3.88 and 1.71, 1.35–2.16 respectively), but not after BNT162b2 (0.59, 0.24–1.45 and 1.00, 0.75–1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1-28 days after ChAdOx1-S were 0.9–3 per million, varying by age and sex. Conclusions Increases in ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic, events were generally lower after either vaccine.