‘Two strategies here’: Epidemiologist Zain Chagla on AstraZeneca and second shots

TVO.org speaks with the infectious-disease expert about new data, expiry dates, and changing vaccine guidelines
By Daniel Kitts - Published on Jun 03, 2021
Zain Chagla is a consultant physician at St. Joseph’s Hospital and Hamilton Health Sciences. (The Agenda)



On Tuesday, the National Advisory Committee on Immunization announced that combining one type of COVID-19 vaccine with a dose of a different brand of vaccine is safe and effective. This comes less than two weeks after NACI said the opposite and advised people to take the same vaccine for both doses. 

It’s not surprising that guidelines have been regularly adjusted: researchers generally have years to develop and test a vaccine, before slowly rolling it out over many months. The first vaccine approved for use in Canada — Pfizer-BioNTech — got the go-ahead on December 9, 2020, only months after the pandemic began.

Still, that leaves Ontarians with many questions. On Tuesday, Steve Paikin spoke with Nicole Lurie, director of the Coalition for Epidemic Preparedness Innovations in the United States, about the various vaccines out there: 

Agenda With Steve Paikin segment, June 1, 2021: The truth about COVID-19 vaccines

For some specific analysis of NACI’s decision to change its advice on vaccines in Canada, TVO.org spoke with Zain Chagla, a consultant physician at St. Joseph’s Hospital and Hamilton Health Sciences and an assistant professor of medicine at McMaster University.

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TVO.org: Less than two weeks ago, NACI said your second dose should be the same vaccine as your first. Then, on Tuesday, it came out and said the second dose can a be different vaccine than the first. What's changed in the past two weeks?

Zain Chagla: There are two new papers, one from Spain and one from Germany, showing that a second dose from different vaccine provides likely the same — if not higher — antibody levels. The other part is the recognition that we do need to get people fully vaccinated, and there are going to be a set number of people that are not going to come back for their AstraZeneca vaccine, and we kind of have to get on with it. We offer them something rather than nothing and leaving them in limbo.

TVO.org: How strong, in your view, is the evidence on mixing and matching different COVID-19 vaccines?

Chagla: The German paper was a small study; I think it was 60 people. People in that study that got mixed doses had antibody levels that were actually quite high — in fact, higher that people that got both doses of Pfizer. The Spanish data suggested, in a few hundred patients, antibody levels that are actually slightly higher than boosting with the same vaccine. And then there is a data set [on efficacy] that will be released in the United Kingdom, but its safety data seemed to show that, with a different dose, people got a bit of sore arm and a bit more fever, but nothing too serious.

It's not the perfect data. I wish we had thousands and thousands of numbers. But I think we've come to the realization, and based on some modeling data, that antibody levels are a pretty good surrogate for vaccine efficacy.

TVO.org: So where does this leave people, like me, who have one AstraZeneca shot and need to get a second shot of some kind? 

Chagla: I think there are two strategies here. One is go with the same vaccine for your dose, knowing there’s longer-term data backing up its efficacy and knowing that your risk of clotting after a second dose is one in 600,000 — though in reality, it might end up being bit higher than that. We’re still finding out from the U.K. in terms of their second shots how many are showing up with the clotting issue. But if you want to reduce risk and potentially have efficacy that is potentially even superior, you could take the Pfizer or Moderna, recognizing that the long-term-efficacy data isn’t out there. Again, is it the one that you know or the one that you don't but you think is probably better.

TVO.org: I can't know for sure, but my impression is that the past few weeks have made many people uneasy about AstraZeneca. I have trouble seeing a lot of people taking AstraZeneca as a second dose. So what are we going to do with all these AstraZeneca shots that we have?

Chagla: I think there is a population that wants it. In Hamilton, we had some secondary AstraZeneca-dose clinics on the weekend. And there were lineups. That being said, it may have been due to the fact that those people had access to a second dose before having access to a second dose through the traditional portal.

I think there is something to be said about drawing a line in the sand and saying there are this many people with AstraZeneca out there — 2 million, or something like that — and we're going to reserve a set number of doses for people who want to get their second dose. And, after that point, you're going to be put into a lineup for mRNA vaccines. I think you're probably going to see 25 per cent coming back for the second dose of AstraZeneca. Now that we've figured out our vaccine strategy, we probably need to make sure that we have an ability to address the global vaccine demand. Part of it is putting our line in the sand for how much AstraZeneca we want to take.

TVO.org: I realize experts have tried to be consistent with their messaging, but sometimes what the experts try to communicate and what people hear can be a little different. And, in the past six weeks, the message non-experts have heard regarding AstraZeneca has changed: 1. Take AstraZeneca if it is offered to you; 2. Take AstraZeneca only if you're in a high-risk group; 3. If you took AstraZeneca and are worried about it, chances are you will get an mRNA vaccine for your second dose; 4. If you took AstraZeneca, you should take AstraZeneca for your second dose; and then 5. Getting an mRNA dose after AstraZeneca is really effective. So what guarantees are there that the advice won't change again in two weeks?

Chagla: I think you wrap it up really nicely. This is a global health emergency. So the science changes, right? People that feel like they got shafted because they got AstraZeneca weren’t represented in hospitals and weren’t represented in deaths, at least not significantly. So the vaccine did exactly what it should have done. 

Data changes. But now we're actually seeing real-life human data suggesting that mixing doses is actually an effective strategy, if not better.

TVO.org: Another aspect that has confused some people in the pool of AstraZeneca recipients is the fact that Health Canada recently extended the expiry date of thousands of doses by about a month. How can a vaccine dose be on the verge of expiring but suddenly be considered safe for another month?

Chagla: The expiry dates are a little bit arbitrary. The company puts an expiry date out in terms of when they think, at the highest threshold, you'll have complete, active vaccine. The company sets that number really high so that they're not getting people with vaccine failures, because that obviously looks bad. Health Canada and AstraZeneca, working together, looked at modelling based on how much the vaccine decayed over time. And they saw that, even with that extra-month interval, there was still a sufficient amount of active vaccine to make sure that people would have an active vaccine with their dose.

TVO.org: So what would you say to someone concerned about whether, even though the expiry date has been extended, the vaccine they're getting has gone “stale?”

Chagla: It's almost like some of the products we get at the grocery store where the expiry date is really the best-before date. It's not necessarily that at midnight that night, it's going to go stale. It is a gradual process. The fact that the company and Health Canada — both of which are very conservative bodies — both came to this conclusion … I would be very, very remiss to say that this isn't safe in that sense.

This interview has been condensed and edited for length and clarity.

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