Mixing COVID vaccines safe, despite symptoms: study
Reactions remain mild, but more common in combinations
People who receive one dose each of AstraZeneca and Pfizer COVID-19 vaccines are more likely to feel a bit unwell for a day or so than if they had both doses from the same vaccine, according to early results from a much-anticipated trial.
But any side effects were short-lived and there were no other safety concerns.
At a minimum, the preliminary data suggest mixing AstraZeneca and Pfizer-BioNTech appears safe, even though people are more likely to experience chills, fatigue, headache, feverishness, joint pain and muscle aches than the “non-mixed” group.
The mix-and-match trial led by University of Oxford researchers is being watched by health authorities the world over, including Canada. The results, already shared with Canada's expert panel of vaccine advisers, could make vaccination campaigns more nimble and ease nerves rattled over the risk of remote but serious blood clots linked to AstraZeneca.
Several provinces are now mulling using Pfizer or Moderna as a second dose for those who received AstraZeneca for their first.
However, the researchers said they did not see a clear signal of an increased risk of vaccine-induced thrombotic thrombocytopenia (VITT) on a second dose of AstraZeneca. That would seem to support sticking with AZ for the second dose.
“But of course it's up to every country and their own experience as to what they think will be the best use of these vaccines,” said chief investigator Dr. Matthew Snape, an associate professor in pediatrics and vaccinology at Oxford.
Pfizer and Moderna, both mRNA vaccines, differ from AstraZeneca. They use different approaches. And, until now, there was no data on what happens when you mix them. What happens when a person is primed with one type of vaccine, and then boosted with another?
In a peer-reviewed letter published Wednesday in the Lancet, researchers reported greater “systemic reactogenicity” — or side effects — in the mixed doses group.
In all, 830 people aged 50 and older, including those with mild to moderate underlying health problems, were assigned at random to receive one of four different vaccine combinations: a first dose of AstraZeneca, followed by either Pfizer or a second dose of AstraZeneca; or a first dose of Pfizer, followed by either AstraZeneca or a further shot of Pfizer. People were given vaccines at four- or 12-week dosing intervals.
The driver behind this study was to look at a way of building “flexibility and resilience into the vaccine rollout” in the event of supply problems, Snape said.
People reported stronger reactions to the first dose of AstraZeneca than the first dose of Pfizer, but the second dose of Pfizer produced more side effects than the first. The Pfizer vaccine was also more painful, according to the volunteers' symptom diaries.
But, in what Snape called a “really intriguing finding,” both mixed schedules caused more side effects than the non-mixed doses. After the second dose of AstraZeneca, around 10 per cent of participants reported chills. But if AZ was followed by Pfizer, that increased to 40 per cent. If it was Pfizer followed by Pfizer about 25 per cent had chills; Pfizer followed by AstraZeneca increased it to 45 per cent.
Similar increases were observed for feeling feverishness, headache, fatigue and muscle aches. Participants didn't know what vaccines they were getting.
It's not clear why mixing doses increased the frequency of reactions, or whether or not it has led to a better immune response. Those data are due in June.
“We know that at an individual level that doesn't always apply,” Snape said. “You'd like to think that if you had a really strong vaccine reaction that means you have a better immune response. That correlation isn't as robust as you might expect.”