In a large real-world study, data published as a pre-print on The Lancet server from over one million individuals assessed the incidence rates of blood clotting disorders of thromboembolism and thrombocytopenia, including the very rare thrombosis with thrombocytopenia (TTS) following vaccination with an mRNA vaccine or AstraZeneca’s COVID-19 Vaccine, and compared them with expected rates in a general population and in people with COVID-19.
Safety profiles of AstraZeneca’s COVID-19 Vaccine, and the mRNA-based vaccine were similar and overall favorable. Very rare clotting disorders (TTS) were observed with both vaccines but these were in line with what would be expected in the general population and lower than in those diagnosed with COVID-19.1
Follow-up time was not sufficient to report rates after two doses of AstraZeneca’s COVID-19 Vaccine, though other studies have shown rates of rare blood clotting events to be lower after a second dose.2
Regardless of the vaccine used, the increase in rates of thrombosis among persons infected with COVID-19 was far higher than among those vaccinated. Rates of venous thromboembolism were eight times higher after a diagnosis of COVID-19 infection compared with the expected rate.
Sir Mene Pangalos, Executive Vice President,BioPharmaceuticals R&D, said: “This real-world study offers further evidence of the favorable benefit:risk profile of AstraZeneca’s COVID-19 Vaccine and demonstrates the critical role all COVID-19 vaccines are playing in combatting thepandemic.”
The analysis included 945,941 mRNA participants (778,534 with two doses), 426,272 AstraZeneca’s COVID-19 Vaccine participants, conducted between 27 December 2020 and 19May 2021. It also included 222,710 COVID-19participants identified between 1 September 2020and 1 March 2021, and 4,570,149 backgroundparticipants as of 1 January 2017 from a public health database held in Catalonia, Spain.
The results are in line with recent reports in theMedicines and Healthcare products Regulatory Agency (MHRA) Yellow Card Report, the UKsystem for collecting and monitoring information on safety concerns, which also show low rates of TTS after a second dose.2
No specific risk factors or definitive cause for TTSfollowing COVID-19 vaccination have been identified and AstraZeneca continues to perform and support ongoing investigations of potentialmechanisms. Furthermore, these very rareevents can be managed when symptoms are identified and treated appropriately.3
COVID-19 Vaccine (ChAdOx1-S [recombinant])
COVID-19 Vaccine (ChAdOx1-S [recombinant]) was co-invented by the University of Oxford and its spin-out company, Vaccitech. It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common coldvirus (adenovirus) that causes infections in chimpanzees and contains the genetic materialof the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attackthe SARS-CoV-2 virus if it later infects the body.
The vaccine has been granted a conditional marketing authorization or emergency use in more than 80 countries across six continents. More than 800 million doses of COVID-19 Vaccine AstraZeneca have been supplied to more than 170 countries worldwide, including more than 100 countries through the COVAXFacility.
The WHO EUL was based on pooled analysis for efficacy from 11,636 participants aged 18 yearsand older, accruing 131 symptomatic COVID-19infections from the UK and Brazil Phase III trials conducted by Oxford University. 6
Overall safety was based on an interim analysis of pooled data from four clinical trials conductedin the UK, Brazil and South Africa which included23,745 participants aged 18 years or older. COVID-19 Vaccine (ChAdOx1-S [recombinant]) was well tolerated and there were no serioussafety events confirmed related to the vaccine.The participants were from diverse ethnic and geographic groups who were healthy or had stable underlying medical conditions.
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In the Philippines, the COVID-19 Vaccine (ChAdOx1-S [recombinant]) COVAX Supply has been given ‘emergency use listing’ by the World Health Organization. Similarly, the direct supply has been granted Emergency Use Authorization (EUA) by the Philippine Food and Drug Administration (FDA). This means that there is more evidence to come about this medicine. The World Health Organization and the Philippine FDA will review new informationon this medicine as it becomes available, and the leaflet will be updated as necessary. Please also note that the vaccine cannot be marketed or sold, advertised, and promoted.
References
1. Burn, E (2021) Thromboembolic events and thrombosis with thrombocytopenia after COVID-19 infection and vaccination in Catalonia, Spain. Pre-print Online:https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3886421
2. Bhuyan P., et al., (2021) Thrombosis with thrombocytopenia after second AZD1222 dose: a global safety database analysis of rare cases. The Lancet. Published Online: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01693-7/fulltext
3. MHRA. Coronavirus vaccine – weekly summary of Yellow Card reporting – GOV.UK 1 July Update. Available at:https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine- adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting
4. Bussel, J.B., et al. (2021) Thrombosis with Thrombocytopenia Syndrome (also termed Vaccine- induced Thrombotic Thrombocytopenia):https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia
5. Voysey M, et al; Oxford COVID Vaccine Trial Group. Single-dose administration and the influence of the timing of thebooster dose on immunogenicity and efficacy of ChAdOx1nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021;397 (10277): 881-891. doi: 10.1016/S0140-6736(21)00432-3. Epub 2021 Feb 19. Erratumin: Lancet. 2021; 397 (10277): 880.
6. https://www.who.int/news/item/15-02-2021-who-lists-two-additional-covid-19-vaccines-for-emergency-use-and-covax-roll-out
