Scientists worldwide have been working to produce an effective COVID-19 vaccine. There is increasing concern surrounding the AstraZeneca COVID-19 vaccine making it a controversial vaccine candidate.
The promise of the AstraZeneca COVID-19 vaccine
The AstraZeneca COVID-19 vaccine was developed in partnership with the University of Oxford shortly after the first Canadian and U.S. COVID-19 lockdowns in March 2020. The vaccine contains a weakened version of a common cold virus and essentially teaches the body how to fight the actual COVID-19 virus.
According to the BBC, what makes the AstraZeneca vaccine unique is that this pharmaceutical company is making the vaccine at cost to ensure doses are distributed to low-income countries around the world, unlike other vaccine companies.1
Clinical testing of the AstraZeneca COVID-19 vaccine began in April 23, 2020. There were four randomized controlled studies in the U.K., Brazil, and South Africa. A total of 11,636 individuals aged 18 and older participated in the study, receiving two separate doses of the vaccine. Some participants received two equal doses of the vaccine, some received a smaller dose first followed by a larger dose, and some individuals received a ‘control’ substance (not the vaccine).
A report was published that included the clinical trial’s progress up to November 4, 2020.2 Of the group that received the vaccine, there were no hospital visits that were COVID-19-related. In the group that did not receive the vaccine, there were 10 hospital visits due to COVID-19, two of which were severe COVID-19 cases, and one of these cases ended up being fatal. The overall ability of the vaccine to protect against COVID-19 infection – its efficacy – was found at that time to be 70.4% overall. This efficacy was measured more than 14 days after participants received their second dose and was confirmed with a COVID-19 infection test.
A second report was published that presented findings from the same group of participants, but the new cut-off date was December 7, 2020.3 There were still no COVID-19-related hospitalizations for those that received the vaccine. In those that did not get vaccinated, the hospitalizations related to COVID-19 increased to 15 people. The overall efficacy was calculated at that time to be 66.7% after 14 days of receiving the second dose.
As these reports suggest, the AstraZeneca COVID-19 vaccine showed potential to protect against COVID-19 infection. But, some may argue that 70.4% or 66.7% is not enough to warrant confident global vaccination. Did AstraZeneca find ways to increase the efficacy of their COVID-19 vaccine?
The optimal dose of the Astra Zeneca COVID-19 vaccine
Referring to the initial AstraZeneca clinical trials in the U.K., South Africa and Brazil, there were two groups that received the vaccine: some received two equal doses and some received a small dose followed by a larger dose. The group that received the smaller dose first showed more promise towards fighting against COVID-19 than the group that received two equal doses. How much did these two vaccination plans affect efficacy?
The group that received a smaller dose first and then a larger dose second had a calculated efficacy of 90.0%, while the group that received two equal doses had an overall efficacy of 62.1%.2 These efficacy calculations were made at least 14 days after the second dose was given and confirmed with a COVID-19 infection test.
In terms of asymptomatic infection, the group that received the two unequal doses showed a 58.9% efficacy against COVID-19 infection, while the identical dose group showed a 3.8% efficacy against COVID-19.2
The optimal dosing schedule for the Astra Zeneca COVID-19 vaccine
Throughout the initial clinical trials of the vaccine, the two doses were given at varying time increments. What did they find?
As of the December 7, 2020 cutoff for data analysis, it was calculated that those who received only one standard dose had 76% protection against COVID-19 infection, and this efficacy measurement did not vary from 22 to 90 days after vaccination.3 The presence of COVID-19 antibodies in the blood also did not change between day 22 to 90 after the first standard dose. This data suggests that a dose of the vaccine does not lose its effect up to at least 90 days post-vaccination.
When given an identical second dose less than six weeks later, the vaccine had an efficacy of 54.9%.3 When the second identical dose was given more than 12 weeks later, the vaccine had an efficacy of 82.4%.3
Is the AstraZeneca COVID-19 vaccine safe for all age groups?
This initial clinical trial of the AstraZeneca COVID-19 vaccine focused on adults ages 18 and up. However, only 12.2% of those tested were above age 55.2 To make a more conclusive statement of the safety and effect of the vaccine in older people, more research needs to be done.
How is the Astra Zeneca COVID-19 vaccine being used today?
In the month of March, many countries put a hold on the distribution of the AstraZeneca vaccine, including Denmark, Norway, Iceland, Ireland, Germany, and Thailand. This was in response to reports of very rare blood clots in some individuals who received the vaccine in European countries.
On March 11, 2021, it was reported by the British Medical Journal that an individual in Austria who received the vaccine had multiple blood clots and died in hospital.4 Another Austrian had a blood clot in their lung and was recovering in hospital. On March 10, Denmark reported a death due to blood clots after the AstraZeneca vaccine was received. On March 14, Denmark and Norway also revealed that six individuals who had received the vaccine were experiencing blood clots and low platelet count and they were all under the age of 50. Blood clots can be fatal, and many of these countries have taken precaution in response.
The European Medicines Agency (EMA) published a review on March 31, 2021 of these blood clots. They identified that there is no evidence of causality of thromboembolic events and the AstraZeneca COVID-19 vaccine. They also claimed that since the vaccine works at approximately 70% efficacy, this outweighs the threat of getting one of these rare blood clots.5
What statistics do we have?
As of March 11, 2021, there were five million people vaccinated in the European Economic Area, and of these people, 30 experienced thromboembolic events.6 According to the Vaccines Safety Lead for U.K. Medicines and Healthcare Products, Phil Bryan, of the 11 million vaccinated with the AstraZeneca COVID-19 vaccine in the U.K., the rate of the thromboembolic events is lower than the rate that would be expected in the general population.4 However, as of April 3, 30 cases of blood clotting have been detected in the U.K. alone in individuals who have received the vaccine.
The U.S. took on a phase III clinical trial of the vaccine, including 32,000 participants. AstraZeneca posted the results on March 25: the new revised overall efficacy was 76%, with 100% efficacy against severe or critical hospitalization, and 85% efficacy in symptomatic COVID-19 in those aged 65+.7 However, these calculations were quickly put under review and the results from the U.S. have yet to be made official due to the FDA’s desire to review the raw data. As of April 3, 2021, the vaccine has not yet been approved by the FDA.
On March 29, 2021, the Canadian National Advisory Committee on Immunization (NACI) adjusted the AstraZeneca vaccine rollout restrictions to only those above age 55, according to a CBC press release.8
The EMA encourages individuals who are worried about the potential of blood clotting to review the newly revised product information (hyperlink to https://www.ema.europa.eu/en/medicines/human/EPAR/vaxzevria-previously-covid-19-vaccine-astrazeneca#product-information-section). Although the EMA identified no causal relationship between blood clots and the Astra Zeneca vaccine, they urge those who have received the vaccine to be aware of the risk based on the cases seen in Europe.5
The AstraZeneca websites feature COVID-19 vaccine information tailored to vaccine recipients and healthcare professionals that differ depending on geographical area. Please visit https://www.azcovid-19.com/ for more information.
If you are scheduled to receive the AstraZeneca vaccine and are concerned how it may affect you, speak with your doctor. It is important to understand your own personal risk when selecting a COVID-19 vaccine.
- Walsh, F. (March 25, 2021). Covid vaccine: AstraZeneca updates US vaccine efficacy results. BBC News. Accessed on April 2, 2021. Retrieved from https://www.bbc.com/news/world-us-canada-56521166.
- Voysey, M. et al. (2020). Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa, and the UK. The Lancet; 397(10269): P99-111. Doi: 10.1016/S0140-6736(20)32661-1.
- Voysey, M. et al. (2021). Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine. The Lancet-PrePrint. Available at SSRN: https://ssrn.com/abstract=3777268. Doi: http://dx.doi.org/10.2139/ssrn.3777268.
- Wise J. (2021). Covid-19: European countries suspend use of Oxford-AstraZeneca vaccine after reports of blood clots. The British Medical Journal; 372: n699. Doi: .10.1136/bmj.n699.
- AstraZeneca COVID-19 vaccine: review of very rare cases of unusual blood clots continues. (Mar. 31, 2021). European Medicines Agency. Accessed on April 2, 2021. Retrieved from https://www.ema.europa.eu/en/news/astrazeneca-covid-19-vaccine-review-very-rare-cases-unusual-blood-clots-continues.
- Cases reported in EudraVigilance. COVID-19 Vaccine AstraZeneca: PRAC investigating cases of thromboembolic events – vaccine’s benefits currently still outweigh risks – Update. (Mar. 11, 2021). European Medicines Agency. Accessed on April 2, 2021. Retrieved from https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-prac-investigating-cases-thromboembolic-events-vaccines-benefits.
- AZD1222 US Phase III primary analysis confirms safety and efficacy. (Mar 25 2021). AstraZeneca. Accessed on Apr. 3, 2021. Retrieved from https://www.astrazeneca.com/media-centre/press-releases/2021/azd1222-us-phase-iii-primary-analysis-confirms-safety-and-efficacy.html.
- Miller, A. (Mar 29, 2021). Why Canada is suspending use of AstraZeneca vaccine in people under 55. CBC News. Accessed on Apr. 2, 2021. Retrieved from https://www.cbc.ca/news/health/canada-suspends-astrazeneca-vaccine-covid-19-1.5968657.
- Image by MasterTux from Pixabay