The Oxford AstraZeneca Vaccine - Should You Be Concerned?

The Oxford AstraZeneca vaccine was once viewed as the holy grail, the annihilator of COVID-19, which would bring back normality to the world. However, with emerging reports of blood clots, outdated data, and confusion over efficacy, public confidence in the vaccine is decreasing [1].

What is the reason for these claims? Are they any cause for concern?

How Does the Oxford AstraZeneca Vaccine Work?

The AstraZeneca vaccine uses a chimpanzee virus vector, which is similar to an adenovirus that causes the common cold in chimpanzees, except it has been modified so that it is harmless and unable to replicate. The vector carries the genetic information for a spike protein that is found on the surface of SARS-CoV-2. This spike protein is a good target for vaccines due to its central role in viral infection and presence of many targets for antibodies to bind during an immune response [2].  

Once inside the body the vector delivers the genetic sequence for the spike protein to the body’s cells. Cell machinery then uses the genetic sequence to make an epitope of the spike protein (portion of the spike protein that is able to stimulate an immune response) and present it on it’s own cell surface . Cells of the immune system come along and recognise the epitope as foreign and launch an attack. Some of these immune cells form memory cells that memorise the epitope so that  next time the immune system encounters the spike protein it can launch a rapid attack against the protein before sickness occurs. 

Myth: “The AstraZeneca vaccine can cause COVID-19”

Fact: The AstraZeneca vaccine cannot cause COVID-19. It contains only a small part of COVID-19’s genetic sequence and therefore it is unable to produce a fully functioning virus.

How Effective is the Vaccine?

An interim analysis of clinical trial data showed the vaccine to be 70.4% effective at preventing symptomatic COVID-19 14 days after receiving two doses of the vaccine [3]. It also showed that it was 100% effective at preventing severe COVID-19 21 days after receiving two doses of the vaccine.

There were initial concerns that the vaccine may not be effective in those aged 55 and above, as out of the 11,636 participants included in the interim analysis, most were between 18-55 years old [3]. Whilst the European Medicines Agency (EMA) did recommend the vaccine be used in the EU, they also stated: “there are not yet enough results in older participants (over 55 years old) to provide a figure for how well the vaccine will work in this group” [4]. 

However, in a more recent study with 32,449 participants, 20% of which were aged 65 and above, it was found that the vaccine was 80% effective at preventing symptomatic COVID-19 for those aged 60 and above, and 79% effective on average, meaning that the vaccine is effective in all adults [5]. It is important to note, AstraZeneca had to revise these figures to 76% effective at preventing symptomatic COVID-19 on average and 85% effective at preventing symptomatic COVID-19 in participants aged 65 and above [6]. This was done after reports that they were using outdated data for their analysis, causing a further decline in their reputation [7]. 

For reference, the most current data on how effective the AstraZeneca vaccine is compared to other COVID-19 vaccines can be seen in Table 1.

Table 1 - How AstraZeneca compares against other COVID-19 vaccines.

Vaccine Side Effects

It is pretty much inevitable that a vaccine will cause side effects, yet what is important is that the benefits of having the vaccine outweigh its risks. Fortunately, most of the side effects associated with the AstraZeneca vaccine are mild and disappear after a few days.

In terms of serious adverse events, three cases of transverse myelitis (inflammation of the spinal cord) occurred during the clinical trial that took place in Brazil, Africa, and the UK [3]. In two of these cases, the participants had been given the AstraZeneca vaccine, the other participant was in the control group. These events were initially reported as unexpected serious adverse events and caused a study halt. However, two of these, one in the control group and one in the experimental group, were later deemed to be unrelated. The third case continues to be investigated as a possible link. There was also a participant who had a high fever (>40°C) after the first vaccination, however, they recovered quickly and continued in the study. No deaths related to the vaccine occurred during the study.

GOV.UK reports the most common side effects (occurring in more than 1 to 10 people) are tenderness at the injection site, fatigue, chills, nausea, muscle aches and headaches [12]. They also reported that more side effects were experienced after the first vaccination than the second and side effects were milder and less frequent in those over the age of 65.

What About Blood Clots?

Early in March, a panic frenzy occurred when Denmark suspended the use of the AstraZeneca vaccine after several reports of blood clots [13]. Other countries, including Norway, Bulgaria, Iceland, France, Germany, Italy, Spain, Portugal, Slovenia, and Cyprus also suspended the use of the vaccine [13].

Ann Taylor, the chief medical officer at AstraZeneca, was quick to respond to these claims, stating “Around 17 million people in the EU and UK have now received our vaccine, and the number of cases of blood clots reported in this group is lower than the hundreds of cases that would be expected among the general population” [14].

However, when the EMA investigated these claims their preliminary analysis concluded the vaccine could be linked to very rare cases of blood clots [15].  Even so, they stated that the overall benefits of having the vaccine still outweigh its risks. The exception for this is for those under the age of 30. This is because there appears to be a higher incidence rate of blood clots amongst the younger population [16]. Additionally, the risk of those under 30 dying from COVID-19 is low, therefore the benefits of having the vaccine do not outweigh the rare risk of blood clots for this age group. As a result, the UK is offering an alternative vaccine for those under the age of 30.

Countries that had previously suspended the use of the vaccine appear to also agree with the EMA, with many now reinstating the use of the AstraZeneca vaccine [17]. However, like the UK, some have also imposed age restrictions, and the European Union has even opted to not gather more AstraZeneca vaccines [18].

Conclusion

To conclude…

• Clinical trials have shown the vaccine to be very effective at preventing symptomatic and severe COVID-19, with the most up to date figures suggesting that it’s 76% effective at preventing symptomatic COVID, and 100% effective at preventing severe COVID-19 [6]. For those ages 65 and above the vaccine is even more effective at preventing symptomatic COVID-19 (85%) [6].

• In theory, this means the rollout of the vaccine should cause a decline in COVID-19 related hospital admissions and deaths. It appears this is exactly what is happening; in the UK the first national population study showed just one dose of the vaccine reduced hospital admissions by 94% [19]. The study is still under peer review—however, the results look promising. 

• There does appear to be a very small risk of rare blood clots associated with the vaccine: ~1 in 250,000 [20]. This risk is actually lower than other commonly prescribed drugs, such as oral contraceptives.

• Nonetheless, as the risk of dying from COVID-19 is very low in young adults, it is suggested that they are given an alternative vaccine. 

• In contrast, for those aged 30 and above the experts have agreed that the benefits of having the vaccine outweigh its risks, thus they will continue to be offered the vaccine.

Ultimately, it is up to individuals to decide whether to get vaccinated, however, it is clear that the science shows that the benefits of vaccination in reducing infection and transmission of the virus outweigh any risks and the AstraZeneca vaccine will continue to play a key part in stopping the spread of SARS-CoV-2.

References

[1] M. Smith, "Europeans now see AstraZeneca vaccine as unsafe, following blood clots scare," YouGov, March 22, 2021. [Online]. Available: https://yougov.co.uk/topics/international/articles-reports/2021/03/22/europeans-now-see-astrazeneca-vaccine-unsafe-follo. [Accessed: 27 March 2021].

[2] Y. Huang, C. Yang, X. Xu, W. Xu, and S. Liu, "Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19," Acta Pharmacologica Sinica, vol. 41, no. 9, pp. 1141-1149, 2020.  Available: https://doi.org/10.1038/s41401-020-0485-4.

[3] M. Voysey et al., "Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK," The Lancet, vol. 397, no. 10269, pp. 99-111, 2021. Available: https://doi.org/10.1016/S0140-6736(20)32661-1.

[4] "EMA recommends covid-19 vaccine AstraZeneca for authorisation in the EU," European Medicines Agency, January 29, 2021. [Online]. Available: https://www.ema.europa.eu/en/news/ema-recommends-covid-19-vaccine-astrazeneca-authorisation-eu. [Accessed 27 March 2021].

[5] A. Kemp, "AZD1222 US Phase III trial met primary efficacy endpoint in preventing COVID-19 at interim analysis," AstraZeneca, March 22, 2021. [Online]. Available: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/astrazeneca-us-vaccine-trial-met-primary-endpoint.html#. [Accessed 27 March 2021].

[6] A. Kemp, "AZD1222 US Phase III primary analysis confirms safety and efficacy," AstraZeneca, 2021. [Online] Available: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/azd1222-us-phase-iii-primary-analysis-confirms-safety-and-efficacy.html [Accessed 27 March 2021].

[7] NIAID, "NIAID Statement on AstraZeneca Vaccine," NIAID, March 23, 2021. [Online]. Available at: https://www.nih.gov/news-events/news-releases/niaid-statement-astrazeneca-vaccine. [Accessed 27 March 2021].

[8] F. P. Polack et al., "Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine," The New England Journal of Medicine, vol. 383, no. 27, pp. 2603-2615, 2020. Available: https://doi.org/10.1056/NEJMoa2034577.

[9] L. R. Baden et al., "Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine," The New England Journal of Medicine, vol. 384, no. 5, pp. 403-416, 2021. Available: https://doi.org/10.1056/NEJMoa2035389.

[10] "Janssen Investigational COVID-19 Vaccine: Interim Analysis of Phase 3 Clinical Data Released," NIH, January 29, 2021. [Online]. Available: https://www.nih.gov/news-events/news-releases/janssen-investigational-covid-19-vaccine-interim-analysis-phase-3-clinical-data-released. [Accessed 27 March 2021].

[11] I. Jones and P. Roy, "Sputnik V COVID-19 vaccine candidate appears safe and effective," The Lancet, vol. 397, no. 10275, pp. 642-643, 2021. Available: https://doi.org/10.1016/S0140-6736(21)00191-4.

[12] Medicines & Healthcare products Regulatory Agency. "Information for UK recipients on COVID 19 Vaccine AstraZeneca." GOV.UK. [Online]. Available: https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazeneca/information-for-uk-recipients-on-covid-19-vaccine-astrazeneca#possible-side-effects. [Accessed 27 March 2021].

[13] E. Mahase, "Covid-19: WHO says rollout of AstraZeneca vaccine should continue, as Europe divides over safety," BMJ, vol. 372, p. n728, 2021. Available: https://doi.org/10.1136/bmj.n728.

[14] "Update on the safety of COVID-19 Vaccine AstraZeneca," AstraZeneca, March 14, 2021. [Online]. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/update-on-the-safety-of-covid-19-vaccine-astrazeneca.html. [Accessed 28 March 2021].

[15] "AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets,"European Medicines Agency, April 7, 2021. [Online]. Available: https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood. [Accessed 22 April 2021].

[16] Department of Health & Social Care. "JCVI statement on use of the AstraZeneca COVID-19 vaccine: 7 April 2021," GOV.UK., April 7, 2021. [Online]. Available: https://www.gov.uk/government/publications/use-of-the-astrazeneca-covid-19-vaccine-jcvi-statement/jcvi-statement-on-use-of-the-astrazeneca-covid-19-vaccine-7-april-2021. [Accessed 22 April 2021].

[17] J.Henley, "Spain, Belgium and Italy restrict AstraZeneca Covid vaccine to older people," The Guardian, April 8, 2021. [Online]. Available: https://www.theguardian.com/society/2021/apr/08/spain-belgium-and-italy-restrict-astrazeneca-covid-vaccine-to-older-people. [Accessed 22 April 2021].

[18] P. A. Churm, “European Union opts not to renew Astrazeneca vaccines contract after supply row,” World News, 2021. [Online]. Available: https://www.euronews.com/2021/05/09/european-union-opts-not-to-renew-astrazeneca-vaccines-contract-after-supply-row. [Accessed 10 May 2021].

[19] "First real-world study of COVID-19 Vaccine AstraZeneca demonstrates 94% reduction in hospitalisations,"AstraZeneca, May 10, 2021. [Online]. Available: https://www.astrazeneca.com/media-centre/articles/2021/first-real-world-study-of-covid-19-vaccine-astrazeneca-demonstrates-94-reduction-in-hospitalisations.html#. [Accessed 29 March 2021].

[20] Medicines & Healthcare products Regulatory Agency, "MHRA issues new advice, concluding a possible link between COVID-19 Vaccine AstraZeneca and extremely rare, unlikely to occur blood clots," GOV.UK, April 7, 2021. [Online]. Available: https://www.gov.uk/government/news/mhra-issues-new-advice-concluding-a-possible-link-between-covid-19-vaccine-astrazeneca-and-extremely-rare-unlikely-to-occur-blood-clots#:~:text=The%20MHRA%20's%20scientific%20review,more%20work%20is%20still%20needed. [Accessed 22 April 2021].

Publisher’s Note

Every effort has been made to ensure the accuracy of this information, which is valid at the time of publication. This article is not being continuously updated however, so readers are encouraged to consult up to date public health advice on vaccination in their country.