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Alastair Leyland and Anna Pearce speak to Vittal Katikireddi from the SPHSU about his work examining waning of the AstraZeneca vaccine.
Podcast series from the MRC/CSO Social and Public Health Sciences Unit, University of Glasgow.
Anna Pearce:
Welcome to 15 Minutes on Health Inequalities and a special podcast related to changes and vaccine effectiveness against COVID. I’m Anna Pearce based at the MRC/CSO Social and Public Health Sciences unit and with me is
Alastair Leyland:
Alastair Leyland, also at the Social and Public Health Sciences unit and today we're talking to
Vittal Katikireddi:
Vittal Katikireddi also at the Social and Public Health Sciences unit.
Alastair Leyland:
Thanks, Vittal. Can you tell us, firstly, what prompted you to carry out this piece of research?
Vittal Katikireddi:
At the time there was a lot of debate about how well vaccines are working, so when the Oxford AstraZeneca vaccine first came out, in Scotland we were involved in a piece of research led by Edinburgh, which looked at the real-world effectiveness of the Oxford AstraZeneca vaccine, making use of the fantastic data infrastructure available in Scotland. So, that showed that early on, during the vaccine rollouts, the Oxford AstraZeneca vaccine worked well in protecting people against severe disease. So, in other words, preventing people ending up in hospital or dying. However, there were concerns that the levels of antibody found within people in specific clinical studies, antibody levels seem to be falling over time. And it wasn't really known whether that then translated to decline in protection against clinically important outcomes, so things like ending up in hospital or dying. So that was really a kind of a really important policy question because if actually vaccines tended to diminish in terms of their effectiveness overtime. In other words, if the effectiveness or the level of protection waned, then there was potentially something that could be done about that in terms of providing boosters. So, to inform that decision making, we carried out this study where we analysed Scottish data, but also built on a previous partnership that we'd had with Brazil and researchers in Brazil to carry out a similar analysis in Brazil as well, just to give us greater confidence in the results.
Anna Pearce:
Thanks Vittal, really interesting stuff. Can you tell us briefly what you did?
Vittal Katikireddi:
So, by using data from the whole population of Scotland and also the whole population of Brazil, we looked at the risk of people ending up in hospital or dying as a consequence of COVID and how that varied depending on the length of time since vaccination. So, if someone, for example, was vaccinated in January we looked at what was their risk of being hospitalised or dying in February, but then also in March, April, et cetera. So, and because we have people who are vaccinated at different times, we're able to look at how that risk might change depending on the length of time it's been since someone completed their primary vaccination schedule. So, the original licence for vaccines was to get 2 doses of the Oxford AstraZeneca vaccine, so we looked at the length of time it had been since receiving those two doses.
Alastair Leyland:
You carried out analysis in Scotland and Brazil. What was the added value of using these two countries?
Vittal Katikireddi:
A big challenge with doing research on COVID vaccination is that the roll out of vaccines happened very quickly, but also happened in a step-wise way. So that meant that people at the greatest risks, particularly the elderly, were vaccinated first and then people at a kind of intermediate risk, so older people but maybe not in the oldest group, were vaccinated next and so forth. So, that then means that the people who you can study for the longest time period, the people, the people who were vaccinated earliest and therefore we can look at how long the people who therefore were vaccinated furthest away are also the people at highest risk, so it can be quite difficult then to tease out this issue of is there a problem with waning? Or is it actually an issue of differences in the age of people who were vaccinated first? So, is it an age difference or is it this kind of cohort issue? Added to that complication is the challenge of different variants overtime. So, as the pandemics progressed, there have been, there was the original type of coronavirus that we had, then there was the Alpha variants and then the Delta variants and so forth. So, each of those might have a different level of vaccine protection. So, you also have this added period effect if you like. So, we have quite a challenging situation to try and understand is there waning happening or not. So, by looking across 2 settings it gives you slightly more confidence that actually what you're observing is waning and not just differences in the age group of the vaccinated or differences due to a change in variance. It's not perfect but research never is. But it gives you a bit more confidence that you're actually attributing the findings you're getting to the right explanation.
Alastair Leyland:
Because of the timing of the study, you're looking at effectiveness against the Delta variant in Scotland and mostly the gamma variant in Brazil. But are you able to extrapolate from these results to what this means for the Omicron variant or subsequent variants?
Vittal Katikireddi:
That's a great question. I think it's difficult because each new variant might have quite different, vaccines might work to a differing extent, and we're still not too sure about that. We are actually doing some more recent analysis where we're looking at Omicron specifically. The available data at the moment suggests Omicron is less severe in terms of your likelihood of ending up in hospital or dying than Delta, but the issue of vaccine waning, the emerging data seems to suggest you see a similar pattern. So, it does seem like it's likely to be an ongoing issue of waning protection, at least with the current available vaccine.
Alastair Leyland:
And what were your headline findings?
Vittal Katikireddi:
What we found was that the Oxford AstraZeneca vaccine that its protection against severe disease fell over time. So, early on the extent of protection against ending up in hospital or dying as a consequence of COVID, early on, the level of protection you get in the first kind of couple of weeks or so was often about 90/95%. Whereas, by the time you get to around 20 weeks it's roughly down to 50%, 50-60% or thereabouts. So, the extent of protection really did seem to fall quite substantially over the course of that time period. And our research, along with findings from England, helped inform some of the decision making around the rollout of boosters, for example, within the UK.
Anna Pearce:
So as you’ve already mentioned Vittal, the study was carried out in whole of population administrative data and why was it important to be able to do that?
Vittal Katikireddi:
So, one of the important strengths of looking at whole population data is typically when medicines and including vaccines are first being studied, researchers often look at quite atypical people. So, people are often much healthier than the general population, they're often kind of young volunteers, whereas so it might be great to know that vaccines work well in that kind of young, healthy population. But in the real world, it's important to know do they work just as well or not?
Anna Pearce:
So, I think when you were carrying out this research Vittal there was a bit of evidence about waning of the Pfizer vaccine but sort of little or nothing about AstraZeneca. What have subsequent studies found and how does that compare to the findings of your paper?
Vittal Katikireddi:
So, I think subsequent studies have generally come to a similar conclusion. They have generally found that protection against severe disease has been, did fall off quite markedly after two doses. So, that's been seen in analysis within, for example England but also there was a subsequent paper in The Lancet based on Swedish data, which came to a similar conclusion as we did. So, I think there is now a kind of an emerging body of evidence which tends to point in a similar direct.
Alastair Leyland:
The $64,000 question is what is the solution to vaccine waning?
Vittal Katikireddi:
Yes, exactly. So, the ideal solution is to have a more effective vaccine. So, I believe a lot of the vaccine manufacturers are trying to explore creating, if you like, a vaccine 2.0, which is tweaked so that it can be effective over a longer time period, but also ideally more resistant to new variants as well. So, I think that might be the longer-term aspiration. In the in the shorter term, I think we've seen from data in for example Israel, but also in the UK I think as well, it's beginning to emerge that further boosters are needed in terms of maintaining protection. Whether that's best done for the whole population or in a more targeted approach where we try to provide additional boosters to the people at highest risk, I think that that's an important policy question to consider.
Anna Pearce:
Thanks Vittal. So, clearly this is a really important and relevant study. Are you aware of any direct impacts that it's had?
Vittal Katikireddi:
So, as we were doing the study, we were in discussions with the UK's JCVI, so the Joint Committee on the Vaccines and Immunisations, and so we were kind of regularly sending through our interim results and so forth to the Chair of the JCVI, but also with organisations like the World Health Organisation and the Brazilian Ministry of Health and so forth. So, I think our data but combined with for example the data from what was then Public Health England probably informed the decision to go for a booster campaign.
Anna Pearce:
So as always, we'd like to finish by asking what are the implications of this work for health inequalities?
Vittal Katikireddi:
In terms of socioeconomic inequalities and COVID, so although we didn't look specifically at the potential for vaccine waning to be different across deprivation groups, because the most deprived groups in Scotland are at the greatest risk of COVID related harms and similarly because ethnic minority groups are at higher risk of severe COVID as well, any fall in protection is likely to hit those groups harder. So just as a consequence of their initial risk being higher, if there's a similar percentage fall in vaccine effectiveness, then that will actually have a greater impact on their absolute risk of severe disease. So, that's an important consideration. However, there are other aspects of inequalities which we did look at directly. So, for example, age-related inequalities, so we know that older people are at much greater risk of severe COVID. But also gender related inequalities. So, men are at more risk of severe cover than women, and also men tend to die younger so there is a potential for narrowing inequalities in terms of those dimensions. There's a kind of broader issue here of global health inequalities. And health inequalities between countries. So, I did struggle a little bit with thinking about well, how do we balance this need for ensuring rapid and equitable roll out of vaccinations at a global level. So, in particular within Africa and the tendency to administer increasing numbers of boosters within high income countries. To some extent I think the boosters within the UK and in most countries are MRNA boosters, which are tending not to be used within low income settings just because the coal chain requirements and so forth are much more stringent. So that tension may not always actually in reality be there. But I do think there is more work needed to address the largely political barriers to roll out at a global level.
Alastair Leyland:
That's great. Thanks very much for talking to us Vittal's, fascinating study.
Anna Pearce:
And thanks also to everybody listening. Details about where to find this paper, so this work was published in The Lancet earlier this year, and also information about the participants in this podcast can be found in the podcast notes. Thank you all again.
Alastair Leyland:
Great. Thank you.