The covid-19 vaccine ChAdOx1-S (also called ChAdOx1 nCoV-19), marketed by the pharmaceutical company AstraZeneca, is a viral vector vaccine that was approved for use in the European Union in late January 2021. We published our latest update on the clinical evaluation data available on this vaccine in late February 2021 (> HERE). The vaccine’s efficacy in older adults could not be determined from these data, primarily obtained from comparative clinical trials in which most participants were younger than 55 years of age.

The UK’s covid-19 vaccination campaign began on 8 December 2020, using tozinameran (Comirnaty°), a vaccine marketed by the pharmaceutical companies Pfizer and BioNTech. The ChAdOx1-S vaccine was authorised in the UK in late December 2020.

The public health agencies Public Health Scotland and Public Health England conducted epidemiological studies to measure the effectiveness of their vaccination strategies (1,2). The results available publicly as of early March 2021 provide useful information on the efficacy of these vaccines during the first weeks after the vaccination of older adults. Although epidemiological studies provide weaker evidence than randomised clinical trials, the two sources are complementary.

Short-term results from Scotland: in the population aged 65 years or older, fewer hospitalisations for covid-19 after vaccination. The authors of this study analysed data compiled from various health databases on 5.4 million Scots (99% of the population of Scotland), including data on vaccination, data collected in general practice, laboratory results, hospital data and death registry data (1). Most vaccinees in Scotland over the age of 70 years, and about 30% of vaccinees aged 65 to 70 years, received the ChAdOx1-S vaccine (1).

The vaccinated group in this study had received a single dose of covid-19 vaccine between 8 December 2020 and 15 February 2021. About 1.1 million Scots (35% of the population) received their first dose of vaccine during this period (1). Anyone confirmed before 8 December 2020 to have been infected with the coronavirus Sars-CoV-2 was excluded from the analysis. 47% of vaccinees were aged between 65 and 79 years (versus only 7% in the unvaccinated group), and 18% of vaccinees were aged 80 years or older (versus only 2% in the unvaccinated group). The risk of developing a severe form of covid-19, mostly due to health problems considered risk factors for severe disease, was higher overall in the vaccinated group than in the unvaccinated group.

The outcome analysed in this study was hospital admission for covid-19, within 28 days of a positive PCR test for Sars-CoV-2 infection, during an epidemic wave in Scotland between 8 December 2020 and 15 February 2021. The authors compared the rates of hospitalisation for covid-19 of vaccinated versus unvaccinated individuals, after taking into account a variety of factors such as age, sex, socioeconomic status, risk factors for severe disease, and also the number of PCR tests performed (1).

Hospitalisation for covid-19 appeared far less common in the population who had received one dose of the covid-19 vaccine ChAdOx1-S than in the unvaccinated population. The relative difference between these two populations increased over time from about 70% (95% confidence interval (95CI) 63%-76%) during the 2nd week after vaccination to about 94% (95CI 73%-99%) during the 5th week (1). 
The same pattern was observed with one dose of tozinameran: the relative difference in hospitalisation rates between the vaccinated and unvaccinated populations increased from about 38% (95CI 28%-47%) during the 2nd week after vaccination to about 85% (95CI 76%-91%) during the 5th week (1).
 In the population aged 80 or over, the relative difference in the rates of hospitalisation for covid-19 between those who had received their first dose of ChAdOx1-S and those who had not been vaccinated increased from about 67% (95CI 59%-74%) during the 2nd week after vaccination to about 81% (95CI 65%-90%) during the 5th week.

Almost as many 65- to 79-year-olds received the ChAdOx1-S vaccine as received tozinameran. It is impossible to distinguish the respective effects of each vaccine from the results available (1).

Short-term results from England: fewer hospitalisations for covid-19 among vaccinees over 80 years of age. Another study, with a case-control design, analysed data from about 150 000 residents of England, aged 70 years or older, who had had at least one PCR test as outpatients after developing symptoms of covid-19 (2).

Vaccine effectiveness was estimated by comparing the vaccination status of the symptomatic individuals who had a positive PCR result (31 718 positive tests taken into account) with that of individuals with the same symptoms but a negative PCR result (62 728 negative tests taken into account), after adjustment for various confounding factors that were similar to those used in the Scottish study. The “UK variant” of Sars-CoV-2, also known as 20I/501Y.V1, had become the dominant strain during the period studied (December 2020 to February 2021).

According to this analysis, in the population aged 70 years or older, the incidence of symptomatic covid-19 appeared markedly lower in patients who had received a single dose of the covid-19 vaccine ChAdOx1-S at least 4 weeks previously than in unvaccinated controls. The follow-up in this study was too short to evaluate the efficacy of the vaccine with sufficient statistical power beyond the 7th week. In the population aged 80 years or older, vaccination appeared to be associated with a lower risk of hospitalisation for covid-19 (2).

The adverse effects reported with the covid-19 vaccine ChAdOx1-S in the UK. As of mid-March 2021, some cases of serious venous thromboembolic events have been reported in Europe in patients who had received the covid-19 vaccine ChAdOx1-S. As of 15 March 2021, the conclusions of the investigations to confirm or rule out the potential role of the vaccine in these cases had not been made public. To interpret these data, it will be necessary to take into account how often serious thrombotic events occur in the absence of vaccination, as well as other factors that may cause thrombosis, such as an underlying disease, risk factors or other medications.

The ChAdOx1-S vaccine has been used extensively in the UK. The national Medicines and Healthcare Products Regulatory Agency (MHRA) has been publishing weekly updates since 5 February 2021, summarising the adverse events reported with each covid-19 vaccine (3). The update dated 11 March 2021 covers the adverse events reported up to 28 February, at a time when about 10.7 million first doses of tozinameran (the covid-19 vaccine marketed by BioNTech/Pfizer) and about 9.7 million first doses of ChAdOx1-S (marketed by AstraZeneca) had been administered (4). 

This report shows no particular safety signals and, in particular, shows no signs of thrombotic or embolic events after administration of the vaccine ChAdOx1-S. For example:

• 
the “Blood disorders" section contains 2 cases of coagulopathy and 35 cases of thrombocytopenia;

• the “Ischaemic coronary artery disorders" section lists 67 cases, 17 of which were fatal;

• the “Pulmonary thrombotic and embolic conditions” and “Non-site specific embolism and thrombosis” sections mention 18 cases, 2 of which were fatal; and

• the "Peripheral embolism and thrombosis" section contains 19 cases (5).


No safety signals for thrombosis were detected in the trials submitted in support of the marketing authorisation application. Events of this type were rare in both the vaccinated groups and the control groups (6,7). 

As of 28 February 2021, the number of reports concerning a thrombotic disorder following administration of the vaccine ChAdOx1-S was of the same magnitude as the number received for tozinameran (8).

The MHRA analysis dated 11 March 2021 states that, after reviewing the data on each of the 275 deaths reported after administration of ChAdOx1-S, none had been attributed to the vaccine, and that there are no indications from isolated reports or series of reports of serious adverse events that were any higher than the rates usually observed over the same period (4).

After the announcement by the Danish drug regulatory agency that a patient had died of thrombosis after receiving the covid-19 vaccine ChAdOx1-S, the European Medicines Agency (EMA) reported that, as of 10 March 2021, at a time when about 5 million people had received this vaccine in the European Union, it was aware of 30 cases of thromboembolic events (9). On 13 March 2021, the French Health Products Agency (ANSM) also issued a reassuring announcement, using data that took account of which batch of vaccine had been used (10).  
 
In practice. These epidemiological data, obtained in the UK after conducting a mass vaccination campaign from late 2020 to early 2021, show that the risk of developing covid-19 of sufficient severity to require hospitalisation is markedly reduced by the covid-19 vaccine ChAdOx1-S, marketed by AstraZeneca, even in older adults, and even when the “UK variant” is highly prevalent. Although epidemiological data provide weaker evidence than clinical trials, they support the use of this vaccine in adults over the age of 65 years, despite the uncertainties inherent to the lack of long-term data and the possible emergence of new variants. In addition, the pharmacovigilance data available publicly at 15 March 2021 are consistent with the adverse effect profile that emerged during the comparative trials.  

©Prescrire 15 March 2021

Sources:

• "Vaccin covid-19 de la firme AstraZeneca : données épidémiologiques britanniques chez les personnes âgées, et données de pharmacovigilance utiles" Application Prescrire 15 March 2021.

1. Vasileiou E et coll. "Effectiveness of first dose of covid-19 vaccines against hospital admissions in Scotland: national prospective cohort study of 5.4 million people" 2 March 2021; ssrn.com/abstract=3789264.
2. Bernal JL et coll. "Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England" 2 March 2021 ; doi.org/10.1101/2021.03.01.21252652.
3. MHRA "Coronavirus (COVID-19) vaccine adverse reactions" 11 March 2021. > HERE
4. MHRA "Coronavirus vaccine - weekly summary of Yellow Card reporting" 11 March 2021. > HERE
5. MHRA "COVID-19 vaccine AstraZeneca analysis print. All UK spontaneous reports received between 4/01/21 and 28/02/21 for COVID-19 vaccine Oxford University/AstraZeneca" 9 March 2021. > HERE
6. MHRA "Public assessment report. Authorisation for temporary supply covid-19 vaccine AstraZeneca, solution for injection in multidose container covid-19 Vaccine (ChAdOx1-S [recombinant])" 22 février 2021.
7. EMA "EPAR- COVID-19 Vaccine AstraZeneca" 29 janvier 2021.
8. MHRA "COVID-19 mRNA Pfizer- BioNTech vaccine analysis print. All UK spontaneous reports received between 9/12/20 and 28/02/21 for mRNA Pfizer/BioNTech vaccine" 9 March 2021. > HERE
9. EMA "COVID-19 Vaccine AstraZeneca : PRAC investigating cases of thromboembolic events - vaccine's benefits currently still outweigh risks. Update" 11 March 2021. > HERE
10. ANSM "Point de situation sur le lot ABV5300 du vaccin AstraZeneca contre la covid-19" 13 March 2021. > HERE
     

For more information:

• "Covid-19: Follow Prescrire's independent, evidence-based analysis of the pandemic" > HERE