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

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 ≥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 ≥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 ≥70 years, rates of arterial or venous thrombotic, events were generally lower after either vaccine.

Risk of thrombosis with thrombocytopenia syndrome after COVID‐19 vaccination prior to the recognition of vaccine‐induced thrombocytopenia and thrombosis: A self‐controlled case series study in England

“… 11 They detected an increased risk (relative risk [RR], 1.98; 95% CI, 1.29‐3.02) of thrombocytopenia 0 to 28 days following ChAdOx1, but not for arterial thromboembolic events (RR, 0.97; 95% CI, 0.83‐0.11). 11 Similar results were reported in an English SCCS analysis of risk of thrombocytopenia (incidence rate ratio [IRR], 1.33; 95% CI, 1.19–1.47) and venous thromboembolism (IRR, 1.10; 95% CI, 1.02‐1.18) 8 , 9 , 10 , 11 , 12 , 13 , 14 days after ChAdOx1 vaccination. 12 The same study also found the risks of hematologic and vascular events to be substantially higher after SARS‐CoV‐2 infection than after vaccination.…”

“…Indeed, the published UK experience of VITT recognizes 220 definite and probable cases over a similar time period. 10 However, multiple large population‐based analyses have found increased risk of hematologic and vascular events that led to hospital admission or death in the weeks following first doses of the ChAdOx1 nCoV‐19 in the United Kingdom 11 , 12 , 13 and Catalonia, 14 and higher than expected rates of cerebral venous sinus thrombosis (CVST) in the ChAdOx1‐vaccinated population in Denmark and Norway. 3 …”

Understanding COVID-19 trajectories from a nationwide linked electronic health record cohort of 56 million people: phenotypes, severity, waves & vaccination

“…COVID-19 testing and treatment has been carried out through a number of different routes which have evolved during the pandemic and our findings illustrate the importance of linking multiple data sources to maximise event ascertainment, fully capturing the spectrum of potential health outcomes and identifying patient transitions through the healthcare system. The phenotypes presented here have already enabled other analyses with highly-relevant public health policy implications such as assessing the association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, and thrombocytopenic events 17 , and evaluating the use of antithrombotic medication on COVID-19 outcomes 18 and studying the incidence of vascular diseases post COVID-19 infection 19 .…”

“…The findings presented are therefore not associative statements and should not be interpreted as causal relationships. However by sharing reproducible phenotype definitions we hope to facilitate further work to address the questions raised in this and other COVID-19 studies exploring national level data, as exemplified by recent research [17][18][19] .…”