Mixing COVID-19 vaccines - which is happening in some countries - linked to worse and more frequent side effects, study says

Mixing COVID-19 vaccines - which is happening in some countries - linked to worse and more frequent side effects, study says
A healthcare worker in the Netherlands is given the Pfizer-BioNTech vaccine on January 6.Piroschka van de Wouw/Pool via AP
  • Mixing the AstraZeneca and Pfizer vaccines was linked to more side effects, an Oxford study found.
  • Some countries in Europe advise mixing doses after limiting the use of the AstraZeneca shot.
  • The symptoms, though unpleasant, were not dangerous, a study author said.

People who mixed doses of the Pfizer-BioNTech and Oxford University-AstraZeneca vaccines get worse versions of the common, flu-like side effects, a UK study found.

The scientists said in a press release that countries mixing and matching the vaccines should be prepared for more people having to take time off work after getting their second dose.

The findings came from early results of the Com-COV study, which looks at the effects of mixing the Pfizer-BioNTech and Oxford-AstraZeneca vaccines.

It found that mild and moderate reactions to the vaccine, such as fatigue and headache, were more frequent when the vaccines were mixed versus getting two rounds of the same shot.

This was the case regardless of which vaccine came first.


Here are some of the reactions reported after the second dose of the vaccine:

  • Feverishness (mild and moderate) - Pfizer/Pfizer: 21%, AstraZeneca/AstraZeneca: 10%, Pfizer/AstraZeneca: 41%, AstraZeneca/Pfizer: 34%
  • Fatigue (mild and moderate) - Pfizer/Pfizer: 55%, AstraZeneca/AstraZeneca: 50%, Pfizer/AstraZeneca: 68%, AstraZeneca/Pfizer: 77%
  • Chills (mild and moderate) - Pfizer/Pfizer: 24%, AstraZeneca/AstraZeneca: 12%, Pfizer/AstraZeneca: 46%, AstraZeneca/Pfizer: 38%

Some countries, such as France, Germany, and the UK, recommend vaccine-mixing in some capacity.

Most often the advice is that younger people who had a first dose of the Oxford-AstraZeneca vaccine should receive a different dose for their second. The policies come from concerns about unusual blood clots identified in a handful of people who had received the Oxford-AstraZeneca vaccine.

Describing the results, the study author and Oxford professor Matthew Snape told reporters that the side effects "are more or less the same type of reactions that we're seeing with the standard schedules - it's just that they are occuring more frequently."

The symptoms went away within 48 hours, Snape said. None of the people in the study were hospitalized, the scientists said.


Snape said a more fundamental question about vaccine-mixing - whether it gives better protection from COVID-19 - was still unknown.

One suggestion was that vaccine-mixing might lead to short-term practical problems, like people calling in sick to work.

"One of the things its telling us is, for example, is that you wouldn't want to immune a ward full of nurses with a mixed schedule because you may have higher rates of absentees in the next day," Snape told reporters.

Severe fatigue - serious enough to seek help from a doctor - was found in roughly 10% of participants when the vaccine doses were mixed, up from about 3% in other participants, Snape said.

But he noted that these were interim results of the study and that no statistical analysis had been done on the numbers, so the figures should be taken with a grain of salt.


The study was run on participants over the age of 50, and the vaccines were given four weeks apart.

It is possible the reactions to mixing the vaccines would be more severe in younger groups, which generally get more side effects, Snape said.

The findings, published as a letter in the peer-reviewed journal The Lancet on Thursday, are from the Com-COV study.

Future experiments are planned to test whether spacing out the doses to 12 weeks would change things.