Mixing COVID-19 vaccine doses leads to more reactions, study finds, which may be ‘first sign of success’

‘We don’t know yet’ whether early finding ties to improved immune response, U.K. researcher says

Lauren Pelley · CBC News · Posted: May 12, 2021

Mixing different types of COVID-19 vaccines can hike the chance of someone having mild or moderate reactions like fatigue, headache or a fever, according to early results from a U.K. study. (Evan Mitsui/CBC)


[Excerpts] Mixing different types of COVID-19 vaccines for two doses can hike the chance of someone having mild or moderate reactions like fatigue, headache or a fever, according to early results from a U.K. study, which is being watched closely by health officials in Canada and beyond.

The findings were published Wednesday as correspondence, not as a full study, in The Lancet — a peer-reviewed medical journal — and came from the Oxford Vaccine Group’s Com-Cov vaccine trial, which is studying the use of different combinations of approved COVID-19 vaccines for first and second doses.

More than 800 participants, all aged 50 or older, were recruited in February, divided up, and given one of four dosing schedules at an either four- or 12-week interval:

  • First and second dose of AstraZeneca-Oxford vaccine.
  • First and second dose of Pfizer-BioNTech vaccine.
  • First dose of AstraZeneca-Oxford vaccine, second dose of Pfizer-BioNTech vaccine.
  • First dose of Pfizer-BioNTech vaccine, second dose of AstraZeneca-Oxford vaccine.

“Both of the mixed schedules caused more symptoms than the standard schedules,” said study leader Dr. Matthew Snape, an associate professor in general pediatrics and vaccinology at the University of Oxford, during a media briefing on Wednesday before the publication of those early results.

“Most of these effects are mild,” he said, though the findings did also show an increase in moderate reactions.

Impact on immune response not yet known

The participant-blinded, randomized trial has been taking place at a network of trial sites across the U.K., with more findings to come. This first round only shows the impact on post-vaccination reactions — not the overall safety or effectiveness of each mix-and-match approach.

“Whether or not this will relate to actually an improved immune response, we don’t know yet,” Snape said. “We’ll be finding out those results in a few weeks’ time.”

Small sample size

However, Horacio Bach, an infectious diseases expert at the University of British Columbia, warned the small size of the initial study does not make it possible to know whether some people would get severe reactions from mixing the two studied vaccines.

AstraZeneca-Oxford, for example, was tested during clinical trials in about 32,000 people, but rare blood clots were not detected until millions of people received the vaccine.

Canada exploring mixing doses

The early findings have emerged at a pivotal time in Canada’s vaccine rollout, when health officials are now reviewing the emerging research on mixing various COVID-19 shots as multiple provinces are gearing up to start swapping in different brands for second doses.

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Mixing COVID-19 vaccine doses leads to more reactions, study finds, which may be ‘first sign of success’