Mixing Pfizer and AstraZeneca jabs 'could worsen side effects'

Mixing and matching Pfizer and AstraZeneca Covid jabs could lead to more short-term side effects like headaches, fever and muscle pain, study finds

  • Oxford researchers found alternating jabs led to more side-effects from jabs
  • Experts said this may be a sign that the vaccines were more effective
  • But added suffering no side-effects does not mean a jab did not work

Mixing and matching Covid vaccines could lead to more side effects, scientists say.

British guidance says people should be given two doses of the same jab because of a lack of data on alternating doses.

But there are ongoing trials of giving one type for the first dose and a different type for the second, to see if it makes them work better or could help countries smooth out bumpy supply chains.

Oxford researchers found people jabbed with AstraZeneca then Pfizer, or the other way around, were more likely to report symptoms like fever, chills or headaches.

There is not yet any data showing whether the mixed dosing regimes made the jabs more effective.

Experts say side effects could indicate a stronger immune response but add that this is not a clear link.

Despite Britain not currently advising mixing and matching, other countries, such as France, have offered AstraZeneca recipients a top-up with Pfizer’s vaccine because of blood clot scares. 

There have been several cases where NHS vaccinators have ended up administering the wrong second dose but it is not believed to cause any safety issues.

More than 35.5million Britons have received at least one dose of a Covid vaccine and 18.4m have been fully vaccinated.

Oxford scientists found that alternating Covid vaccine types for the first and second doses appeared led to more people claiming they felt side effects (Pictured: A nurse fills a syringe with vaccine)

The Com-COV study found alternating jabs sparked an increase in side-effects. The above table shows the rate of different side effects by group, which each included about 110 people. ChAd refers to AstraZeneca’s vaccine, and BNT to Pfizer’s jab. Most notable are more reports of fatigue and malaise (tiredness), fever, headache, joint pain and muscle ache

The decision to delay doses has allowed the UK to achieve one of the most successful vaccine programmes in the world. More than 35million Britons – over half the entire population – have already been given at least a one dose and a further 18m are fully jabbed

Professor Matthew Snape, a vaccinologist and chief investigator on the study, told a briefing that the team ‘don’t know yet’ whether higher rates of side effects mean the vaccine is triggering a stronger immune response.

‘The full picture will become apparent when we have the antibody readout as well, and then we can see whether or not this had led to an improved immune response,’ he said.

‘We know that at individual level that doesn’t always apply, but you’d like to think that if you’d had a really strong vaccine reaction and had fever and so on that means you have a better immune response.


The coronavirus vaccine programme in England will open up to people under the age of 40 for the first time tomorrow.

NHS England said around a million adults aged 38 and 39 will be invited to come forward for their jab from Thursday morning.

They will be offered either the Pfizer or Moderna vaccine on the back of guidance from medical regulators last week.

The Joint Committee on Vaccination and Immunisation (JCVI) said under-40s should be given an alternative to the AstraZeneca jab due to its link to rare blood clots.

The NHS Digital bulletin said 38 and 39-year-olds already booked in for a first dose of the British vaccine will have their appointment cancelled.

People who qualify for a jab will be invited via a text from ‘NHSvaccine’, which includes a web link to the health service’s online booking service.

Those who can’t access the internet can call 119 instead to get an appointment at one of 1,600 sites administering the vaccines across England.

So far more than a quarter of the entire UK population – 18.1million – has been fully vaccinated against Covid and more than half – 35m – have received the first dose.

NHS national medical director Professor Stephen Powis said the success of the rollout was owed to ‘careful planning and precision of NHS staff’.

‘That correlation isn’t as robust as you might expect.’

The Com-COV trial, full name Comparing Covid Vaccine Schedule Combinations, is the first in the world to look at mixing coronavirus jabs.

A total of 463 people aged between 50 and 69 were enrolled in this part of the research and received their jabs four weeks apart.

Results showed 37 of 110 people who got the AstraZeneca then Pfizer dosing regime experienced chills (33 per cent).

And out of the 114 participants who got Pfizer then AstraZeneca, 47 (41 per cent) said they had a fever as a side effect.

For comparison, the rate of fever in people who got two doses of the AstraZeneca jab was just 10 per cent (11 of 112).

And among those who got two doses of the Pfizer it was 21 per cent (24 out of 112).

‘These data suggest that the two vaccine schedules in this trial might have some short-term disadvantages,’ the team wrote.

‘Regardless, it is reassuring all symptoms were short-lived and there were no concerns from the limited data available.’

Data presented in the academic paper suggested fatigue and malaise, fever, headache, joint pain and muscle ache were all reported more often from people who had a mixed vaccine schedule.  

Professor Snape said last month: ‘The risk with mixing is you’re going to see suboptimal immune responses, or a response that is not as good as in the original vaccine course.

‘I, personally, would be surprised if that was the case, [but] we just don’t know what the outcome will be yet.’ 

The results were published in a letter to prestigious journal The Lancet, ahead of the release of the full data next month. 

He suggested there was a risk that mixing vaccines could lead to more workplace absences, which was important to consider for key workers like nurses and doctors.

Side effects were reported as only mild or moderate in the vast majority of cases and the scientists said they identified no safety concerns with mixing the jabs. 

Of people involved in this arm of the study, 212 were women and 117 were men. Around a quarter took paracetamol to reduce symptoms.

Professor Matthew Snape said they were yet to establish if alternating doses made vaccines more effective

Clinical trials show both the AstraZeneca and Pfizer vaccine can trigger side effects including fever, headache and muscle soreness, but that these are short-lived.

These figures are just one arm of the Com-COV study, which is also looking at alternating doses using the Moderna and Novavax shots.

Scientists also plan to test blood samples for Covid antibody levels, to see whether the alternated jabs sparked a stronger immune response. 

AstraZeneca’s vaccine was 76 per cent effective at blocking symptomatic Covid infections in clinical trials, compared to 92 per cent for Moderna’s and 95 per cent for Pfizer’s.

Experts point out these results are ‘very good’ for any vaccine, adding the World Health Organization only set the bar at 50 per cent and annual flu jabs are often only around 40 per cent effective.

AstraZeneca’s and Novavax’s jabs uses a cold-modified virus containing Covid spike proteins to teach the immune system how to fight off the disease.

While Pfizer and Moderna’s jab uses mRNA — instructions for building proteins — to trigger production of the spike particle.

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