One dose of Pfizer plus one dose of AstraZeneca safe, but more mild side-effects reported: study

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TORONTO — Preliminary results from a study in the U.K. suggest that receiving your second dose of the COVID-19 vaccine from a different brand than the first dose is safe — but it could be more likely to give you mild side-effects such as a headache, chills or a fever.

The study looked at more than 800 adults aged 50 and over who had received mixed vaccine doses at a four-week interval. The early results were described in a research letter in the journal The Lancet on Wednesday.

Researchers found that with the two mixed schedules they were looking at — Pfizer followed by AstraZeneca, and AstraZeneca followed by Pfizer — both resulted in more frequent side-effects after the second dose when compared to ‘non-mixed’ schedules.

There are no results yet on how effective the vaccines are when administered in this way. Data on efficacy is expected to arrive next month.

The study found a noted increase in temporary problems, including fever and fatigue, after receiving the shot.

"We're seeing growth more frequently, both in mild and moderate symptoms, but they resolved quickly,” Matthew Snape, associate professor in pediatrics and vaccinology at the University of Oxford, and the chief investigator of the study, told CTV News.

These adverse reactions ranged from mild to moderate, but were short-lived, researchers say. No major safety concerns were found.

“These are the type of reactions we do expect, […] and they are more or less the same types of reactions that you're seeing with the standard schedules for vaccines,” Snape said. “They're [just] occurring more frequently.”

Dr. Theresa Tam, Canada’s chief public health officer, told CTV News Channel on Wednesday evening that these early results look “like a good first sign in terms of favourable use.

“We are monitoring that data really carefully,” she said of the U.K. study, adding that a recommendation from NACI will come once more data from the study has been released. “Early indications are looking favourable.”

Although she cautioned that we need to wait for data on the immune response to know for sure, she said it was a “possibility” that Canadians could be receiving mixed schedules of vaccine doses this summer.

Most people who got vaccinated in the U.K. study didn’t experience moderate symptoms, Snape explained, but the number of people who did was higher in their study among those who had a mixed vaccine schedule.

The most important takeaway from these early results is that people who receive a mixed vaccine schedule may need to plan more time off around their shot.

“This is just telling us about how you should manage the first few days after immunization, whether it's at the individual level, you know what you can expect, or, for example at a healthcare provider level, as I say, you don't immunize a whole floor of nurses with the mixed schedule because you might have higher absenteeism the next day,” Snape said. “So it's more of that kind of informing what to expect a few days after immunization, rather than a safety signal of anything that's going to have any longer term implications.”

This data was presented to countries, including Canada, which are considering mixing and matching vaccines, Snape said.

“There are quite a lot of countries that are thinking of using these mixed schedules, […] and they may need to prepare […] to have some high rates of absenteeism,” Snape said.

It’s still good news for Canadians who have already received AstraZeneca and are unsure whether to take it for their second dose, or even whether supply will allow for that.

Several provinces, including Ontario, Alberta, Saskatchewan and Manitoba, have stopped offering AstraZeneca as a first dose.

The approach is changing because of a shortage of supply, but also because the risk of developing serious blood clots after the first AstraZeneca dose has been found to be less rare than previously thought, calculated now in Ontario as one in 55,000.

Provinces are now waiting for guidance from scientific agencies on how to proceed with doses that they do have.

“For the moment, with a small number of doses that we already have, we're just holding on to them, pending the final review by NACI and Health Canada,” Christine Elliott, Ontario’s health minister, said Wednesday.

Part of that review will be looking if it's safe to give a different vaccine as a second dose, making these new results more important.

Tania Watts, a professor of immunology at the University of Toronto who received AstraZeneca for her first shot, is among those who feel bolstered by the early results from the U.K. study.

“The first thing is that it's safe to mix and match, there's nothing dangerous that has come out, no surprise about some strange reaction,” Watts told CTV News. “The surprise is that actually you get more of these systemic effects such as fever and chills and headaches.”

If you received Pfizer for your first shot, for example, Watts said you should probably go with Pfizer for your second shot, but if you received AstraZeneca for your first shot and are uncertain of supply for the second dose, the data supports receiving Pfizer for your second dose.

“If you're like me and you had AstraZeneca first, then if Pfizer comes available, then you have to just consider that and it seems like it's safe,” Watts said.

In the U.K. study, those on a mixed schedule who received AstraZeneca as their second booster shot experienced slightly higher levels of side effects than those who received Pfizer as their second booster shot, with 47 per cent of those who received AstraZeneca after Pfizer reporting that they felt feverish, compared to 34 per cent of those who received Pfizer after AstraZeneca.

Participants self-reported on their symptoms in the days following their vaccine doses, and the majority of reported symptoms occurred in the 48 hours after receiving a shot.

Snape explained that within the study, mild symptoms were defined as “not having much impact on their daily activities” while moderate symptoms have more of an impact on their daily life, but the person is still able to function.

Around 17 to 20 per cent experienced temporary symptoms severe enough to impact their daily life, with the side effect most often reported being fatigue.

“They're tired enough they felt they couldn't undertake their daily lives,” Snape said.

Not many people reported chills or feeling feverish to a degree that it interrupted their lives.

“I'm often asked, what's the difference between fever and feverish. Fever is the objective sign of somebody measuring the temperature and finding it's about 38 degrees, feverishness is the feeling like you have a fever, and we all know that feeling. It's certainly interesting to note that actually even though they're feeling hot or cold, a sense of feverishness, actually relatively few did have a fever.”

In the next stage of the study, where they are looking at a 12-week interval between doses, they will be asking participants more about the impact on their lives and if they had to take the next day off of work, among other things.

The most important data is still to come — whether mixing and matching gives equally good or even better immunity than one brand for both shots — with results on this question expected to be released in June.

“The full picture will become more apparent when we have the antibody readout as well and we can see […] whether or not this has led to an improved immune response,” Snape said.