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

By William Whiteley, Samantha Ip, Jennifer Anne Cooper, Thomas Bolton, Spencer Keene, Venexia M Walker, Rachel Denholm, Ashley Akbari, Efosa Omigie, Sam Hollings, Emanuele Di Angelantonio, Spiros Denaxas, Angela Wood, Jonathan AC Sterne, Cathie Sudlow, CVD-COVID-UK consortium

Posted 23 Aug 2021
medRxiv DOI: 10.1101/2021.08.18.21262222

ABSTRACT Importance: Thromboses after the COVID-19 vaccine ChAdOx1-S have been reported. Better understanding of population-level thrombotic risks after COVID-19 vaccination is needed. Objective: Quantify associations of vaccination with ChAdOx1-S and BNT162b2 with major arterial, venous and thrombocytopenic events. Design: Cohort study based on linked electronic health records, with follow up from December 8th, 2020, to March 18th, 2021. Setting and participants: Adults registered with an NHS general practice in England and alive on December 8th, 2020. Exposures: First dose of vaccination with ChAdOx1-S and BNT162b2. Main Outcomes and Measures: Incidence rates and hazard ratios (HRs) for major arterial, venous and thrombocytopenic outcomes 1-28 and >28 days after first vaccination with ChAdOx1-S or BNT162b2 vaccine. Analyses were performed separately for ages <70 and [&ge;]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 pre-vaccination rates, at ages <70 and [&ge;]70 respectively, were 0.97 (95% CI: 0.9-1.05) 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 pre-vaccination. 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 and Relevance: Increases in ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years are 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 [&ge;]70 years, rates of arterial or venous thrombotic, events were generally lower after either vaccine.

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