The recent modification to the Australian COVID-19 AstraZeneca vaccine rollout to the 60-69 year age group reinforces key foundational pieces in any mass immunisation campaign.

While it may not have been the news we had hoped for, this change shows that our Australian vaccine safety surveillance system is both robust and constantly adapting to the latest available evidence. The main safety challenge with a large population wide rollout is detecting and responding to safety signals which may not be evident in a clinical trial. The TGA and state-based surveillance systems, such as SAEFVIC in Victoria, are actively identifying and providing information for groups like ATAGI to come to clinical safety decisions.

Australians want to know that our rollout is underpinned by a robust safety vaccine system, and any previous and future changes to the rollout system should be viewed in this context.

It also reinforces the importance of the risk-benefit ratio, which is a dynamic evolving concept based on both an individual’s and a population’s circumstances at that point in time. That has underpinned this most recent change, where the risks of vaccination with AstraZeneca in this age group, no matter how small, outweigh the potential benefits because of Australia’s current low rate of COVID-19 disease. Importantly, this risk-benefit balance may change again in the future - should circumstances change.

While scientifically based, any change is likely to be frustrating for some and cause hesitancy around COVID-19 vaccination in others. The importance of building vaccine confidence in the population at this juncture is more crucial than ever. There is an abundance of resources available for the community, both about vaccination in general and also specifically about TTS, to ensure everyone can understand and evaluate the latest rollout change for themselves together with their health practitioner. It will require a creative nuanced effort between experts, government and the general public to boost collective confidence.

• Am I at risk if I’ve had AZ and I’m in my 50’s?

No, if you have had the first dose and 3-4 weeks have passed, then you are past the time frame for most thrombotic responses. These are seen after the first dose but not second boost.

• Will I be at risk if I don’t have the second AZ dose?

Yes, you will have reduced protection against SARS-CoV-2 and hence still susceptible to infection when we open our borders or get community cases of SARS-CoV-2.

• Can I mix a first dose of AZ with a second dose of something else? Will it be safe, and will it be effective?

Theoretically yes, however, there are no clinical trials to demonstrate if efficacy is comparable. Also depends on what the vaccine providers will allow, but in the US mixing of primary and secondary vaccines has occurred – since the main objective was to quickly get good vaccine coverage.

• Will this increase vaccine hesitancy?

Undoubtedly, I think the 50–60-year-olds will feel uncomfortable and annoyed that they ‘feel’ they have been put at increased risk. It will undoubtedly increase scepticism that the government and scientists know what they are doing. But in reality, this is real science, and recommendations change as more information becomes available, situations change and the risk/benefit for vaccination changes. Of note, I think the recommendation for AstraZeneca in the UK was >45…. A different risk/benefit scenario and hence different recommendation.

• Will this affect our efforts to achieve a good proportion of community immunisation in a timely fashion, especially if alternative vaccines are in short supply?

Yes, as AstraZeneca was our initial major supplier. However, seems the government has alternative arrangements in place to cover this short-fall in supply for <60’s.

• Will COVID-19 get away from us, especially the variants, because of this change?

I do not believe that at present there is a threat to vaccine efficacy due to the variants of concern. Maybe minor effects, but breadth of responses should still give protective immunity in my opinion.

ATAGI has made the right decision in acting on new risk information. The aim is to keep people as safe as possible and minimise risk. It shows a strong commitment to vaccine safety and responsiveness. The system is working. It was clearly a difficult decision given the implications in a limited supply environment, but it was needed in view of the new information on the risk of the rare clotting syndrome -  TTS - being slightly higher in the 50-59 year old age group than first thought.

The implication of this recommendation is that it will increase demand on the Pfizer vaccine. Minister Hunt has been quoted as saying there are 1.2 million people in the  50 to 59 year old age group yet to be vaccinated. Until we get enough supply, some may not be able to access Pfizer when they want to, particularly in the younger age groups. This will intensify during outbreaks when we see a surge in vaccine demand. For the most part, we hope that most jurisdictions can manage the extra demand until we see a ramp-up in supply later in the year.
 
It is inevitable that some more people will feel more cautious about this vaccine, particularly those already hesitant. This is likely to be a minority.
 
There were also many Australians still getting vaccinated with the previous announcement. For those over 60 years who are hesitant about AstraZeneca and where it’s the only option for the time being, I would say this: it’s normal to feel concerned about the risk of TTS – it’s serious even though it’s rare. When people have any vaccine, they should look at the advice on early signs of reactions to report for prompt diagnosis and treatment. The big picture is also important. TTS is a risk at a single point in time whereas the benefits of vaccination and the immunity it provides extend into the future, to ourselves, our families and communities.
 
Finally, as we face these issues in Australia with low supply, it’s worth remembering countries in the region with large outbreaks of COVID where there is not enough of any vaccine and a slow trickle expected. I think keeping perspective is important for us as we consider our role as global citizens and good neighbours.

The recent advice from The Australian Technical Advisory Group on Immunisation (ATAGI) that the AstraZeneca vaccine (now called Vaxzevria) should only be used for those 60 years or over is in line with recent advice from the European Medicines Agency (EMA) that nearly all cases of the rare clotting disorder have been in women under 60 years of age. However, this will again disrupt the vaccine rollout, since Pfizer vaccine supplies are limited, and we are unlikely to get additional Pfizer vaccine, or for that matter, Moderna or Novavax until much later this year. Unfortunately, the Federal Government put most of their eggs in the AstraZeneca basket, and this is now becoming a major problem. 

The EMA also point out that the rare clotting disorders mostly occur after the first dose, so the risk for those under 60 who have already had their first dose and now getting their second dose is likely to be very small. There are clinical trials underway of the use of Pfizer as a second dose after AstraZeneca, and early results look good. So, this potentially will be another option once the full data are available. Finally, a recent report from the UK has found that both the Pfizer and AstraZeneca vaccines appear to be equally effective against hospitalisation after being infected by the delta (Indian) variant.   

Currently, there is a requirement to get 2 doses of the vaccines approved for use against COVID-19 in Australia for full immunity. For those of us in our 50s who have already received one dose of AstraZeneca vaccine, we should be able to get the Pfizer vaccine as the second dose. Both vaccines allow protein expression of the SARS-CoV2 spike and present this to our immune systems.

Other countries have introduced one shot vaccines like the Johnson and Johnson vaccine, which has also been shown to be effective.

In theory, boosters make our immune responses stronger and induce memory. They refine the type of antibodies we make to bind the virus with higher affinity and specificity. Updated booster shots aim to tweak our antibody responses but will also be able to provide broad immunity against variants of the virus, even those that have yet to emerge. This happens because the common regions of the base of the spike protein remain the same in each jab.

A quest for a universal vaccine against COVID-19 is the holy grail. This type of vaccine would not require regular updates in vaccine design and boosters could be administered in multivalent vaccines, perhaps with annual influenza vaccination.

We will have to learn to protect ourselves from COVID-19 and live with this virus in our future.

The principle behind an age cut off relates to the assessment of risks versus benefits of the AstraZeneca vaccine. While the rare clotting syndrome known as TTS still has an overall low incidence, it does appear to be increased relatively in those that are younger.

The opposite age correlation holds true for severe consequences of COVID-19, meaning that the older you are, the more likely you are to have a worse outcome from infection. Therefore while it is likely the benefits of this vaccine in the form of protection from COVID-19 (particularly severe disease) still outweigh the risks overall, the difference between benefits and risks, is greater as you get older.

Our regulatory bodies comprised of many genuine experts in this area constantly monitor the risks of vaccines in the form of adverse events, both in Australia and abroad, as well as the benefits in terms of the risk of catching COVID-19.

In our country we are fortunate to have excellent control of the virus and therefore a very low background rate of severe disease. We also are fortunate enough to have an alternate vaccine in the form of Pfizer, albeit still in relatively short supply. Putting this all together it made sense to bring in an age cut-off, one that considered all of these variables and one that was always subject to change as the situation evolved.

We know for example that with a higher risk of COVID-19, some countries introduced a younger cut-off even as low as 30 years of age. Out of an abundance of caution and considering all of these and other factors, it would seem a sensible decision to increase the age cut-off for the use of this vaccine in our country at present. It is important to appreciate however that this may be subject to further changes in the future, in either direction, as the situation around us continue to evolve.

In terms of the safety of this vaccine, our ability to recognise and manage this rare clotting syndrome has increased dramatically since it was first recognised so consequently the outcomes have improved. We must keep in mind that this is a highly effective vaccine and it remains safe in the population in which we are using it, so if you are eligible for this vaccine, this change in how it is being used should not dissuade you from doing so.