Why are the age recommendations constantly changing? Does this cause VIPIT blood clots? Is it effective against variants?

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Vaccine boxes in a larger shipping box


Many people have questions about the evolution of AstraZeneca’s COVID-19 vaccine usage guidelines. Here are some answers from infectious disease specialist Dr Alexander Wong.

How is the AstraZeneca vaccine different from other COVID-19 vaccines?

ChADOx1 nCoV-19 / AZD1222 (AstraZeneca’s COVID-19 vaccine, also known as the Oxford-AstraZeneca and COVISHIELD vaccine) uses a modified adenovirus ‘vector’ to provide the genetic code for the SARS-CoV-2 spike protein to the cell nucleus. This vector has been modified to be able to enter human cells, but once inside it cannot replicate. This means that it cannot endanger the recipient of the vaccine.

Once inside the cell, the spike protein DNA is delivered to the nucleus of the cell. There, the code is translated into messenger RNA (mRNA) which the cell can then use to make its own spike proteins.

These advanced proteins then help stimulate the body’s immune system to develop antibodies. It is these antibodies that protect us from infections and serious illnesses when we are exposed to the SARS-CoV-2 virus.

New Brunswick Premier Blaine Higgs receives the Oxford-AstraZeneca COVID-19 vaccine in Fredericton on March 31. The vaccine is administered by Brenda Tree of Pharmacy for Life.
THE CANADIAN PRESS / Stephen MacGillivray

The AstraZeneca vaccine is different from mRNA vaccines (such as Pfizer-BioNTech and Moderna). The adenovirus “vector” and the DNA code that the vector carries are much more resilient and resistant than the lipid particles that contain the fragile mRNA code to be delivered into cells with the Pfizer-BioNTech and Moderna vaccines.

This leads to several practical advantages with the AstraZeneca vaccine over mRNA vaccines – it does not need to stay frozen when stored and it can last for months at normal refrigerator temperature. It is also cheaper to produce in large quantities.

The AstraZeneca vaccine was 70% effective against symptomatic COVID-19 infection in a large multinational study. Another large study conducted primarily in the United States recently reported 76% overall effectiveness against symptomatic COVID-19.


Also read: COVID-19 Vaccines: How Pfizer and Moderna’s 95% Effective mRNA Injections Work


Although these efficacy data are slightly lower than the reported efficacy of mRNA vaccines, AstraZeneca vaccine is quite effective in preventing serious illnesses and hospitalizations, like mRNA vaccines.

The overall efficacy differences between AstraZeneca vaccine and mRNA vaccines are minor. For most people in Canada, the best vaccine is usually the one offered to you first, especially in the midst of the third wave currently going through the country.

Why has its use been suspended in some regions? Is it related to blood clots?

In early March, reports from various countries in the European Union linked the use of the AstraZeneca vaccine to the potential for rare but potentially fatal blood clots, known as “vaccine-induced prothrombotic immune thrombocytopenia” or VIPIT. German data suggests an incidence rate of about one in 90,000 shots. A recent update from the European Medicines Agency suggests an incidence rate of one per 100,000 injections across Europe to date.

Researchers believe the vaccine can cause platelets to clot, similar to a rare occurrence caused by heparin, a blood thinner. Data are still emerging around the potential association between the AstraZeneca vaccine and VIPIT, and the degree of risk remains uncertain.

A healthcare worker holds a vial of AstraZeneca Covishield vaccine at a COVID-19 vaccination clinic in Montreal.
THE CANADIAN PRESS / Paul Chiasson

On March 31, Canada suspended the use of the AstraZeneca vaccine to all people under the age of 55. Germany has done the same, but for all people under the age of 60. The UK has suspended its use in all people under the age of 30.

The reasoning in Canada (and other countries) for the age-related break on AstraZeneca use has to do with a calculation of risk versus benefit for a given individual. The overall risk of death among people under the age of 55 who acquire COVID-19 infection is very low in Canada.

When comparing the risk of death from COVID-19 in younger people versus the risk of VIPIT from the AstraZeneca vaccine, regulators have made the decision to be careful with their advice, especially because Canadians have access to other vaccines such as Moderna and BioNTech-Pfizer and soon Johnson & Johnson Vaccine as well.

As the evidence evolves, the guidelines for using the AstraZeneca vaccine will likely change again.

Why are there different recommendations for different age groups – and why are they constantly changing?

As described in the previous answer, there is an inherent balance between risk and benefit that expert groups had to navigate when advising on AstraZeneca vaccine in the absence of definitive data. As we age, our risk of dying from COVID-19 infection also increases. Thus, the balance between risk and benefit directs towards administration of the vaccine, which significantly reduces the likelihood of serious illness, hospitalization and death.

Among young people, this balance is more complicated, especially now with the widespread dissemination of worrisome variants across Canada. These variants are known to be more transmissible and more deadly.

AstraZeneca COVID-19 vaccine dose boxes at a facility in Milton, Ontario.
THE CANADIAN PRESS / Carlos Osorio – POOL

In early March, initial recommendations from the National Advisory Committee on Immunization (NACI) in Canada suggested that the AstraZeneca vaccine should not be used in people over 65 years of age.

This is because clinical trial data initially reported from December included a very limited number of people over 65, so the effectiveness of the vaccine could not be determined in this age group.

Shortly thereafter, concrete evidence of support generated by the UK was reviewed by NACI and deemed sufficient to illustrate the effectiveness of the AstraZeneca vaccine in people over 65 years of age, and the recommendations were amended accordingly. .

The evolving recommendations from NACI and other guideline groups reflect evolving evidence and science, not the inadequacy of the vaccine itself. This is precisely how post-market surveillance is supposed to work with drugs and vaccines.

However, with this topic under such close scrutiny due to the global pandemic, trying to explain these concepts to the lay public has been a challenge for regulators, government officials and medical professionals.

What should I do if I have already received a dose of the vaccine, but it is no longer recommended for my age group?

At present, this is not clear. Various studies are underway to combine different COVID-19 vaccines, especially in the UK, but there is not yet a good evidence base for this.

Public health guidelines will be updated as more evidence emerges, but if the association between the AstraZeneca vaccine and VIPIT continues to hold up, my best guess is that people in this situation will be offered a second. dose of vaccine, but from a different manufacturer. At present, the current guidelines remain to try not to administer different vaccines at different times, if possible.

Is it effective against newer variants?

Data on the efficacy of the AstraZeneca vaccine against the predominant circulating variants remain limited. Published data from clinical trials suggest that the vaccine remains effective against the B.1.1.7 variant found primarily in the UK, even though the vaccine induced lower blood levels of antibodies to the B.1.1.7 variant compared to to the non-mutated virus.

Preliminary data released in South Africa at a time when the B.1.351 variant was widely circulating suggested that the AstraZeneca vaccine did not have a reduction in the rate of mild to moderate COVID-19 infection in young and healthy people. for the majority. However, the trial included only small numbers overall.

The ability of the AstraZeneca vaccine to limit serious illness and hospitalization against the South African variant could also not be determined in this study due to the very low number of young people who otherwise become seriously ill. More data is needed to better answer this question.

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