COVID-19 Vaccine AstraZeneca

The replication-deficient chimpanzee adenovirus vector AZD1222 is indicated for active immunization of individuals 18 years of age and older for the prevention of 2019 coronavirus disease (COVID-19).

The AstraZeneca vaccine(AZD1222) is a so-called vector vaccine. It consists of harmless chimpanzee-derived cold viruses that contain in their DNA the blueprint for a protein on the surface of the Coronavius SARS-CoV-2. The vector viruses are taken up by cells of the vaccinated organism. This transient transfection leads to the effect that the organism produces the targeted corona spike protein (S-protein) for a short period of time. However, no coronaviruses are produced during this transfection, only antigens. The immune system is stimulated by the presence of the antigens to produce defence substances (antibodies and T cells) against this protein and thus immunity.

AZD1222 is administered intramuscularly into the deltoid muscle at intervals of 4 to 12 weeks (28 to 84 days).

The approval of the Corona vaccine AZD1222 from AstraZeneca is only pronounced for 18- to 64-year-olds. The efficacy in older people has not yet been sufficiently proven. Apart from this limitation, the vaccine is also considered to be equally suitable as the already approved Corona vaccines. (STIKO/EMA).

Storage and shelf life Unopened: 6 months at 2°C to 8°C. After first use, the vaccine should be administered as soon as possible and within 6 hours. The vaccine can be stored between 2°C and 25°C during use

The vaccination regimen consists of two doses of 5 x 1010 virus particles corresponding to 0.5 ml of the vaccine at intervals of at least 4 to a maximum of 12 weeks.

AZD1222 is administered intramuscularly into the deltoid muscle at intervals of 4 to 12 weeks (28 to 84 days).

The most commonly reported adverse reactions in clinical trials were:

Sensitivity at the injection site (> 60%), pain at the injection site, headache, fatigue (> 50%), myalgia, malaise (>40%), pyrexia, chills (>30%), arthralgia, nausea (> 20%). Most side effects were mild to moderate in severity and usually disappeared within a few days after vaccination. Compared to the first dose, reported adverse reactions were milder and less frequent after the second dose.

In older subjects (≥ 65 years), adverse reactions were generally milder and less frequent.

Recent cases of disseminated intravascular coagulopathy (DIC) and sinus vein thrombosis (CVST ) have occurred during vaccination campaigns, nine of which resulted in death. Most of these cases occurred in people under 55 years of age. The majority were women.

Note: As these events are rare and COVID-19 often causes blood clotting disorders even in patients, it is difficult to estimate a background rate for these events in individuals, according to the EMA. However, based on pre-pandemic Corona figures, it was calculated that < than 1 reported case of DIC would have been expected in persons under 50 years of age within 14 days of receiving the vaccine. In fact, 5 cases were reported. For CVST, 1.35 cases would have been expected during this period. However, there were actually 12 patients.

A similar imbalance was not evident in the older population receiving the vaccine.

AZD1222 must not be used in cases of hypersensitivity to the active substance or to one of the excipients:

• L-histidine
• L-histidine hydrochloride monohydrate
• magnesium chloride hexahydrate
• polysorbate 80
• Ethanol
• Sucrose
• Sodium chloride
• Disodium edetate dihydrate
• Water for injection

Study situation: Several studies are available (COV001-COV005) in several thousand patients. An interim analysis of AZD1222 clinical trials included data from the Phase II/III COV002 trial (NCT04400838) in the United Kingdom and the Phase III COV003 trial (NCT04536051) in Brazil. Overall, efficacy as well as safety was evaluated in 23,000 participants aftertwo doses of a half dose (2.5x1010 viral particles) and later a full dose (5x1010 viral particles) or two full doses of AZD1222 versus a comparator meningococcal conjugate vaccine called MenACWY or saline.

Efficacy: Combined analysis of both dosing regimens (n=11,636) showed an average efficacy of 70%. Compared with the other previously approved Corona vaccines, AZD has relatively low efficacy.

Efficacy data in the elderly: The Phase II/III study (COV002) of 560 subjects examined how immunogenic and safe the vaccine was in three age groups (18 to 55 years, 56 to 69 years, over 70 years): 160 subjects were between 18 and 55 years old, another 160 subjects were between 56 and 69 years old, and 240 subjects were 70 years and older. The results were published in The Lancet in November. The study showed that the vaccine was better tolerated in older subjects than younger ones, and that similar immunogenicity was achieved across all age groups after a boost dose. However, it was noted that further assessments were needed to evaluate efficacy in all age groups and individuals with comorbidities.

This was followed by a further publication in The Lancet on 8 December 2020 which addressed the results of the trials (NCT04324606, NCT04400838, and NCT04444674). The conclusion: on efficacy in people aged 65 and over, "there is limited information, although nothing to suggest a lack of protection."

Further information on vaccinations can be found on the websites of the Robert Koch Institute and the Paul Ehrlich Institute.

There is also a detailed collection of questions and answers at Stiftung Warentest.

The vaccination procedure is regulated in the federal states, which have published their own information on this.

1. Barrett JR et al (2020) Oxford COVID Vaccine Trial Group. Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose inducing multifunctional antibody responses. Nat Med doi: 10.1038/s41591-020-01179-4.
2. Folegatti PM et al (2020) Oxford COVID Vaccine Trial Group. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 396(10249):467-478.
3. Knoll MD et al (2021) Oxford-AstraZeneca COVID-19 vaccine efficacy. Lancet 397(10269):72-74.
4. Voysey M et al. (2021) 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. Lancet 397(10269): 99-111.
5. Robert Koch Institute. STIKO decision on the 2nd update of the COVID-19 vaccination recommendation and the associated scientific rationale. Epidemiological Bulletin 5/2021.