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Mixing Covid vaccines increases side effects, finds Oxford trial

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Mixing doses of the AstraZeneca and Pfizer Covid vaccines is more likely to lead to mild and moderate side effects, results suggest.

Researchers from the Com-COV study being led by the University of Oxford said preliminary data from the 830 patients aged 50-69 who were randomised showed more frequent mild to moderate reactions in mixed schedules.

Reporting their data in a research letter in The Lancet, the researchers said that when given at a four-week interval, both of the ‘mixed’ schedules (Pfizer-BioNTech followed by Oxford-AstraZeneca, and visa-versa) induced more frequent reactions following the second ‘boost’ dose than standard schedules.

One in 10 volunteers given two AstraZeneca jabs four weeks apart reported feverishness but this rose to 34% of those receiving one AstraZeneca jab and one Pfizer in any order.

Similar increases were observed for fatigue, headache, joint pain, malaise, and muscle ache.

Any adverse reactions were short lived and there were no other safety concerns from the trial which began recruiting in February.

The trial has now been adapted to assess whether early and regular use of paracetamol reduces the frequency of the reactions and has also since been expanded to include Novavax and Moderna vaccines.

Data is not yet available on the Impact of mixed schedules on immune response, the team said but the first results may be published in June.

Dr Matthew Snape, associate professor in Paediatrics and Vaccinology at the University of Oxford, and Chief Investigator on the trial, said: ‘Whilst this is a secondary part of what we are trying to explore through these studies, it is important that we inform people about these data, especially as these mixed-doses schedules are being considered in several countries.

‘The results from this study suggest that mixed dose schedules could result in an increase in work absences the day after immunisation, and this is important to consider when planning immunisation of health care workers. 

‘Importantly, there are no safety concerns or signals, and this does not tell us if the immune response will be affected.’

The Government commissioned the study, which has to date examined using the AZ and Pfizer vaccines interchangeably through four different combinations, in February.