28 April 2021
On 23 April 2021, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) published its assessment report on the benefit:risk of the AstraZeneca COVID-19 vaccine by gender and age stratification and recommendations on second dose.1
The CHMP assessment report conclude that the overall benefits of the vaccine in the prevention of COVID-19 outweigh risks from adverse events including thrombosis in combination with thrombocytopenia (TTS). The analyses conducted show that the benefits of vaccination increase with increasing age and increasing infection rate, recognising the higher impact of COVID-19 causing severe disease in older populations. The findings of the report are included in the interim opinion and opinion annex.
The CHMP concluded that two separate doses of the vaccine should be administered four to 12 weeks apart, in line with the current product information. CHMP advised the mechanism behind the observed cases of TTS is unclear, and there has not been enough exposure and follow-up time to determine whether the risk of TTS with a second dose will differ from that of the first dose.
This assessment at present contains only interim results and may be subject to change as more is known about the risk of TTS and the favourable effects of vaccination with COVID-19 Vaccine AstraZeneca. However, these results can be used to help guide vaccination decisions at national level including on optimal use of the vaccine.
Understanding the risk:benefit of AstraZeneca’s COVID-19 vaccine
COVID-19 has caused over three million deaths worldwide and it is well known to cause clinical complications such as blood clots and low platelets. Studies from France and the Netherlands suggest that thrombosis occurs in 20-30% of critically ill COVID-19 patients, even when preventative measures are used.2 Similarly, a study from the UK has reported that the risk of rare blood clotting following COVID-19 infection is around 100 times greater than normal.3 A UK study of over 500,000 COVID-19 patients, rare blood clotting events of cerebral venous thrombosis (CVT), also described as CVST in the analysis, occurred in 39 patients per million. This is several times higher than the rate of events that occur after vaccination.
Currently, no confirmed mechanism has been established to explain why a COVID-19 vaccine could cause these extremely rare events of thrombosis with thrombocytopenia. It is too early to draw conclusions on causal links to the adenoviral vector platform used for some of these vaccines, including COVID-19 Vaccine AstraZeneca. AstraZeneca is working with regulators, recommending bodies and the scientific community to understand the individual cases, epidemiology and possible mechanisms that could explain and inform the treatment of these extremely rare events.
1. EMA assessment report, Vaxzevria. April 23rd 2021. Available at: https://www.ema.europa.eu/en/documents/referral/use-vaxzevria-prevent-covid-19-article-53-procedure-assessment-report_en.pdf [Last accessed 27 April 2021]
2. Covid-19 and thrombosis: what do we know about the risks and treatment? BMJ 2020; 369: https://www.bmj.com/content/369/bmj.m205.8 [Last accessed: 26 April 2021]
3. Taquet M, Husain M, Geddes JR, Luciano S, Harrison PJ. Cerebral venous thrombosis: a retrospective cohort study of 513,284 confirmed COVID-19 cases and a comparison with 489,871 people receiving a COVID-19 mRNA vaccine. Pre-print. 2021. [Online] Available at: https://osf.io/a9jdq/. [Last accessed: 26 April 2021