Corona vaccine from AstraZeneca: you should know that!

On January 29, 2021, the coronavirus vaccine jointly developed by AstraZeneca and Oxford University was approved in the EU. The vaccine differs from the previously approved coronavirus vaccines because it is not an mRNA but a vector vaccine. The approval was linked to great expectations because the vaccine can be transported and stored at refrigerator temperature. This means the coronavirus vaccination can also be carried out by the family doctor or at home. However, the vaccine is controversial, partly because cerebral vein thrombosis is a possible side effect. How well does the vaccine protect against COVID-19? What advantages and disadvantages does it offer compared to other vaccines? What else should you know about it? You can find out here.

Corona vaccine from AstraZeneca: what kind of vaccine is it?

The vaccine, called “Vaxzevria” (previously “COVID-19 Vaccine AstraZeneca” and also AZD1222 or ChAdOx1 nCoV-19), was jointly developed by the Swedish-British pharmaceutical company AstraZeneca and the British University of Oxford. It is a so-called vector vaccine, counted among the gene-based vaccines. This technology has already been used with the Ebola vaccine Ervebo and a vaccine against dengue fever.

 

How does the vector vaccine work?

The vaccine consists of the shell of a harmless virus, the so-called vector, and information about the so-called antigen, i.e. the pathogen SARS-CoV-2:

• The vector takes on a transport function: it is needed to introduce the information about the antigen into the cells. In this case, the vector used is the envelope of an adenovirus that cannot reproduce, which causes a cold in chimpanzees but is harmless to humans.
• Inside this shell is the blueprint for a protein characteristic of the SARS-CoV-2 coronavirus, the spike protein found on the coronavirus’s surface. This protein is utterly harmless on its own. It is only used by the virus to dock onto the cells in the human body.

Through the vaccination, our body receives the blueprint for the spike protein and replicates it. Our body’s immune system recognizes these proteins as foreign and fights them – among other things- by forming antibodies and T cells, i.e., various resistant system components.

After a short time, the vaccine and the spike proteins built by the body are entirely broken down. However, the body remembers how to recognize and fight the spike protein. If he later comes into contact with the spike protein again through infection with SARS-CoV-2, the immune system can react immediately and fight the virus.

How well does the AstraZeneca vaccine protect against Corona?

To determine the vaccine’s effectiveness, several studies were conducted with almost 24,000 participants. According to the initial study data relevant to approval, the vaccine has an efficacy of around 60 per cent in the 18 to 55 age group—the risk of contracting COVID-19 when infected with SARS-CoV-2 falls by about 60 per cent with the vaccination.

The data suggest that full vaccination with two doses can almost wholly prevent severe cases of COVID-19 or deaths. The determined effectiveness also applies to people with pre-existing conditions, provided the study data allow a statement in each case.

In principle, it can be assumed that vaccinated people are still contagious, i.e. can transmit the virus, even if they do not contract COVID-19 themselves. However, the risk of transmission is considered to be significantly reduced by vaccination.

 

Effectiveness of 70 per cent: where does this figure come from?

In terms of effectiveness, there was some confusion at first. The initially specified 70 per cent effectiveness was based on the average of various studies in which the participants were accidentally given different doses. As a result of an error, some study participants initially only received half the vaccine dose. With this flawed study design, the vaccine even showed an effectiveness of 90 per cent, while the planned study design only showed an effectiveness of around 62 per cent.

So, is it better to give only half the vaccine dose first? The study data do not allow a statement on this. A possible explanation could be that the body builds up vaccination protection against SARS-CoV-2 through the first vaccination, as well as against the vector virus, which is used as a means of transport. Then, the second vaccination, the so-called booster, would also not work. Therefore, it might make more sense to administer a lower dose initially. However, the difference could also be because the study participants in the higher efficacy group were, on average, younger (up to 55 years old), and the two vaccine doses were given at different intervals. Follow-up studies indicate that it may improve efficacy.

In the meantime, further studies have been carried out and submitted to the authorities for examination. The manufacturer has also conducted additional studies to examine the factors that may have influenced its effectiveness more closely. The European Medicines Agency has decided not to consider the survey with the incorrect vaccine dose. Therefore, an effective rate of only about 60 per cent is currently given, even if it can sometimes be higher. Recent studies suggest, for example, that the effectiveness could be as high as 81 per cent if there were a 12-week interval between the two doses of the vaccine.

How effective is it in older people?

Before the expected approval, doubts about how well the vaccine would work in older people were raised. On the one hand, this group was underrepresented in the original studies, so the currently available data may not allow a clear statement on the effectiveness in older people. On the other hand, the media even reported an effectiveness of only eight per cent in the group of over 65-year-olds.

The manufacturer commented on both points. According to his statement, another study with 2,000 participants, including older people, was submitted to the approval authorities. Two-thirds of the subjects should have been over 75 years old. The oldest participant was 86 years old.

The fact that the vaccine only works in eight per cent of older people is also wrong because the available data show, according to AstraZeneca’s statement, that a robust immune response is also generated in older people. The Federal Ministry of Health also contradicted corresponding reports and stated that no reduced effect for older people could be derived from the available studies. A mix-up was suspected because about eight per cent of the participants were between 56 and 69 years old.

Nevertheless, the Standing Vaccination Committee (STIKO) of the Robert Koch Institute initially recommended that the vaccine only be approved for people between 18 and 64 years of age, as there was not enough data to assess its effectiveness in older people. The European Medicines Agency, on the other hand, recommended approval from the age of 18 without an upper age limit. While she agrees that there is not enough data in older people to assess effectiveness, she based her decision on promising results in other age groups and experience with other vaccines.

On March 4, STIKO changed its recommendation so that the vaccine can also be used for people over 65. The background to this is that there is now sufficient data showing high safety and effectiveness, even in older people.

 

What side effects are possible?

As with any vaccination, side effects can occur after administration of the AstraZeneca vaccine. These include:

• pain at the injection site
• exhaustion and fatigue
• headache
• joint and muscle pain
• chills
• Fever and flu-like symptoms
• discomfort and nausea

These side effects usually go away on their own after a short time. The side effects were generally milder in older study participants.

During the study, one subject developed spinal cord inflammation (transverse myelitis). The study was then interrupted until a team of experts ruled out a connection with the vaccination.

As with other vaccines, severe allergic reactions in the form of anaphylactic shock are also possible in rare cases. Therefore, an observation period of at least 15 minutes is recommended after vaccination so that medical treatment can be initiated as quickly as possible in the event of an allergic reaction.

Serious side effects were observed in less than one per cent of the study participants. Since infrequent side effects cannot usually be detected in such a study due to their low frequency, the responsible authorities will continue to examine all suspicious activity reports even after the vaccine has been approved. They determine whether there is a connection to the coronavirus vaccination or whether symptoms arose purely by chance shortly after the vaccination. This is in line with standard practice when approving new vaccines and medicines.

Therefore, in September 2021, Guillain-Barré syndrome, a nerve disease, was added to the list of infrequent side effects. Less than 1 in 10,000 people are affected by this side effect. Since January 2022, transverse myelitis has also been listed as a possible consequence. It is a rare neurological disorder in which symptoms such as weakness in the arms and legs, abnormal sensations ( numbness, tingling, pain, etc.) or impaired bowel or bladder function can occur as a result of inflammation of the spinal cord.

 

Are late effects possible?

Even though the AstraZeneca vaccine is already being used in several countries to vaccinate against SARS-CoV-2, it is a comparatively new vaccine. Therefore, as with other vaccines against COVID-19, no statements can be made about long-term effects.

However, according to current scientific knowledge, long-term effects, i.e. side effects that only occur after a more extended period, are not to be expected. The reason lies in how vaccines work: Since, unlike drugs, they are not administered constantly over a more extended period, they are broken down again very quickly, which is why side effects occur after a few weeks at the latest. In the past, vaccines have never had a long-term impact. Long-term consequences, which arise as side effects after a short time and last for a more extended period, must be distinguished from this.

Thrombosis: blood clots as a side effect?

Vaccination with the AstraZeneca vaccine or specific batches of the vaccine was temporarily halted in several countries in March after some cases of blood clots in vaccinated individuals and isolated deaths from various types of thrombosis.

Whether there is a causal connection to the vaccination is currently being investigated. It could also be a random occurrence: statistically speaking, the number of blood clots is no higher than expected from the many vaccinated people, even without vaccination.

However, there is a particular form of thrombosis, the frequent occurrence of which, in connection with vaccination, cannot be explained by chance alone. These so-called sinus vein thromboses (or cerebral vein thromboses) are usually extremely rare, so their increase quickly became the focus of the responsible authorities. Pulmonary embolism as a result of thrombosis has also been observed in several cases.

Vaccination stopped due to cerebral vein thrombosis.

Following a corresponding recommendation from the German Paul Ehrlich Institute (PEI), the Federal Ministry of Health also announced on March 15, 2021, that vaccinations with the AstraZeneca vaccine would be suspended until further testing by the European Medicines Agency (EMA) was available. The reason was that up to this point, seven cases of cerebral vein thrombosis had been recorded in Germany. Although this is extremely rare, it is still above average when you look at the statistics. Younger women, in particular, were affected.

The EMA continued to recommend the vaccine after a re-examination. A connection between vaccination and cerebral vein thrombosis has not been proven, but it cannot be ruled out. Due to its rarity and the risks posed by COVID-19 to unvaccinated individuals, EMA estimates that the benefits of vaccination far outweigh the potential risks. However, doctors should be aware of the possible side effects and inform the people to be vaccinated about it. Federal Health Minister Jens Spahn then announced on March 18 that the vaccination campaign with the vaccine would be continued.

However, after further cases of cerebral vein thrombosis had occurred, the STIKO changed its recommendation on March 30 to initially only use the vaccine in Germany in people over 60. Younger people could still receive the vaccine after individual consideration. Up to this point, 31 rare sinus vein thrombosis cases had occurred, primarily in women under 55.

On April 7, the EMA confirmed a possible connection but, in principle, continues to recommend the vaccine unreservedly, as its benefits far outweigh the potential risks. The frequency is given as 1 case per 100,000 vaccinations.

 

What is sinus vein thrombosis?

The so-called sinus vein thrombosis is a unique form of thrombosis in which one of the sizeable venous blood vessels in the brain (sinus veins) is blocked by a thrombosis, i.e. a blood clot. In this context, so-called thrombocytopenia was also observed, i.e. a lack of blood platelets ( thrombocytes ).

The complication is called vaccine-induced immune thrombotic thrombocytopenia (VITT). In addition to sinus vein thrombosis, thrombosis can occur in other body areas. Strokes are also a possible consequence of such a thrombosis, as reported by British doctors.

Scientists suspect that the vaccine triggers immune responses in some people through autoimmune antibodies, as a result of which the blood platelets are activated and clump together. This is usually done as part of wound healing to stop bleeding from blood clotting. In this case, however, the falsely activated mechanism leads to the formation of blood clots in the brain. What happens is very similar to what is known as heparin-induced thrombocytopenia (HIT), which is usually due to the active ingredient heparin.

According to current knowledge, a reaction of an endogenous protein from blood platelets, called platelet factor 4 (PF4), with the vaccine and the subsequent formation of antibodies against PF4 is responsible for frequent sinus vein thrombosis.

Such a form of thrombosis can be treated with medication, but it can also lead to death.

Already vaccinated with the AstraZeneca vaccine – now what?

People who have already been vaccinated – significantly younger people under 50 – should pay close attention to possible side effects in the 16 days after the vaccination. This also includes bruises or punctiform skin haemorrhages (petechiae), which could be a first warning signal for a low number of thrombocytes (blood platelets). Anyone experiencing side effects such as headaches and discomfort more than four days after the vaccination should seek medical advice.

For younger people who have already received their first vaccination with the vaccine, the Standing Vaccination Commission recommends using an mRNA vaccine for the second vaccination.

Capillary Leak Syndrome: side effect of Clarkson Syndrome

It can be assumed that there is a connection between vaccination and sporadic capillary leak syndrome (also called Clarkson syndrome or capillary leak syndrome). This is a vascular disease in which the capillaries are too permeable for plasma and plasma proteins to leak out. As a result, oedema can occur, the blood can thicken due to the loss of plasma water, and blood pressure can drop.

Isolated cases of Clarkson’s syndrome have been observed in the context of vaccination. A particular risk exists if those affected have already suffered from the syndrome in the past. In these cases, the administration of the vaccine is not recommended. AstraZeneca published a Red Hand letter on this in June 2021.

 

Impurities are a possible cause of side effects.

Researchers at Ulm University Hospital announced in May that they had found numerous impurities when examining Vaxzevria samples. Viral and human proteins, which were not part of the adenovirus vector, were found, including so-called heat shock proteins.

These could provide a clue as to how the thrombotic thrombocytopenias observed in rare cases after vaccination with the vaccine came about. According to one theory of the Ulm researchers, the vaccine itself might not be the trigger for the formation of thrombosis with consumption of the blood platelets. Still, instead, the proteins found would initiate a process that ultimately leads to thrombosis. Further studies should now clarify whether such a connection exists.

How does the vaccination work?

The vaccine is injected into the muscles of the upper arm. Two shots are required for complete protection, with the second dose given within four to 12 weeks of the first. The Standing Vaccination Commission recommends keeping a nine to twelve-week gap between the two vaccinations.

According to the approval, a shortening of the vaccination interval to up to four weeks is possible. Still, experts view it critically since the study data suggest that a longer interval between the two vaccination doses is associated with greater effectiveness. Shortening the vaccination interval, for example, to take advantage of the legal advantages of being fully vaccinated earlier, is generally not recommended.

A second vaccination with mRNA vaccine is recommended.

On July 1, 2021, STIKO recommended using an mRNA vaccine as a second vaccination for all people who have already received a first vaccination with Vaxzevria. This recommendation had long been in place for people under 60 who had received the AstraZeneca vaccine as their first vaccination before the decision was made to only use the vaccine for older people in the future.

The background to this recommendation is that such a “heterologous vaccination scheme” or “cross-vaccination” causes the immune response to be more robust and thus provides a better protective effect. The interval between the two vaccinations should be at least four weeks. However, according to the current study, normal vaccination reactions such as headaches or tiredness could be reduced with a longer interval.

The third vaccination should also be carried out with an mRNA vaccine – regardless of which vaccine was used for the first two vaccinations.

 

Comparison with mRNA vaccines: advantages and disadvantages

To vaccinate the population as quickly as possible and contain the coronavirus pandemic, it is necessary to use several vaccines simultaneously. At the same time, several manufacturers were working flat out on various approaches to developing a coronavirus vaccine. The result is different vaccines, each with distinct advantages and disadvantages.

Here are the advantages and disadvantages of the AstraZeneca vaccine compared to the two already approved mRNA vaccines from BioNTech/Pfizer and Moderna :

Advantages:

• Refrigeration: The vaccine can be transported and stored at refrigerator temperature (2 to 8°C). It is, therefore, also suitable for vaccinations in the doctor’s office or at home and is associated with significantly fewer logistical difficulties than the two mRNA vaccines that have been approved so far.
• Price: At around two euros per dose, the vaccine is significantly cheaper than the mRNA vaccines at about 15 euros.
• Suitability for poorer regions: Both the lower price and the simpler refrigeration mean that the vaccine is also likely suitable for use in poorer countries.

Disadvantages:

• Efficacy:  With only 60 per cent efficacy, the vaccine compares poorly to the already approved mRNA vaccines from BioNTech/Pfizer and Moderna (about 95 per cent efficacy). However, it should be emphasized that this vaccine can also effectively prevent severe and fatal courses.
• Protection against virus mutation: Study data indicate that the vaccine offers little protection against mild and moderate cases of virus mutation beta (B.1.351) originating in South Africa. It remains to be clarified how good the protective effect is against severe courses. The protective effect is likely reduced with other virus variants as well. The protective effect can be improved by combining it with an mRNA vaccine as a second vaccination.
• Side effects:  Compared to other vaccines, the vaccine has substantial side effects, especially in younger people. In sporadic cases, cerebral vein thrombosis could also occur as a result. The vaccine is, therefore, only recommended in Germany for people over 60.

Who is the AstraZeneca vaccine approved for?

The vaccine received emergency use authorization in the UK in December 2020. The vaccine has also been used in some other countries for a long time.

In the European Union (EU), vaccine testing by the European Medicines Agency began in October 2020. The EU Commission decided on conditional market approval on January 29, 2021, after the EMA issued a recommendation for approval on the same day.

Based on the available study data, the vaccine may be used in the EU for people over 18, so children and adolescents may not be vaccinated. People with an immune deficiency or severe chronic diseases, as well as pregnant women and nursing mothers, were also excluded from the vaccine study. As such, there is no evidence of their safety regarding the AstraZeneca vaccine.

According to the recommendations of the STIKO, the AstraZeneca vaccine should initially only be used in Germany for people up to a maximum age of 64 years. For this reason, the vaccination ordinance was revised so that members of risk groups between 18 and 64 should preferably be vaccinated with the AstraZeneca vaccine. In contrast, the already approved mRNA vaccines from BioNTech/Pfizer and Moderna should be used primarily for older people. However, after the STIKO gave the green light for use in people aged 65 and over, the vaccination ordinance was amended accordingly on March 10.

Due to individual reports of thrombosis of the cerebral veins, the Federal Ministry of Health decided on March 15 to stop using the AstraZeneca vaccine until the connections were examined more closely. After reviewing the connections by the EMA, it was announced on March 18 that vaccinations with the vaccine would be resumed. On March 30, however, the STIKO changed its recommendation that the vaccine should initially only be vaccinated in people aged 60 and over.

However, after individual risk assessment and medical advice, the vaccine can also be used in younger people aged 18 and over. For this reason, the prioritization of the AstraZeneca vaccine was cancelled on May 6, 2021, so that from now on, younger people who do not belong to any of the prioritized vaccination groups could also be vaccinated with it at their request.