Here's What We Know About Mixing Covid Vaccines So Far

The first results of the Covid vaccine mixing trial – where doses of both the AstraZeneca and Pfizer jabs were given – are in.

Mixing doses of the Pfizer and AstraZeneca vaccines appears to increase the likelihood of you suffering side effects, according to preliminary data from the vaccine mixing trials.

Data from the University of Oxford-led Com-COV study shows more frequent mild to moderate reactions in mixed schedules compared to standard schedules where people have had two doses of the same vaccine.

What’s the aim of the study?

The Com-Cov study launched in February to investigate alternating doses of the Oxford/AstraZeneca vaccine and the Pfizer/BioNTech vaccine. In April, it announced the programme would be extended to include the Moderna and Novavax vaccines.

The aim of the trial is to explore whether the Covid-19 vaccines can be used more flexibly, with different vaccines being used for the first and second dose. This would mean if there were supply issues, alternatives could be offered.

England’s deputy chief medical officer, Professor Jonathan Van-Tam, previously said it’s even possible that “by combining vaccines, the immune response could be enhanced giving even higher antibody levels that last longer” – although this is only a theory and hasn’t been proven.

What did the study find?

The trial recruited 830 volunteers aged 50+ from various areas in England. The study confirmed people are more likely to have side effects after the first dose of AstraZeneca than the first dose of Pfizer. It also showed people were more likely to get side effects after the second dose of the Pfizer jab, compared to the first.

When given at a four-week interval, both of the ‘mixed’ schedules – Pfizer followed by AstraZeneca, and AstraZeneca followed by Pfizer – induced more frequent mild and moderate side effects following the second ‘boost’ dose than the standard schedules. Mild side effects were those that didn’t have much impact on study participants’ daily activities, while moderate side effects had “some impact” on their daily activities.

Both of the mixed schedules caused more symptoms than the standard schedules, particularly when it came to systemic reactions – so things like chills, fatigue, fever, headache and joint pain.

Researchers noted a possibility that side effects from mixing doses may be more prevalent in younger age groups. This is because data has so far shown that when people do suffer side effects from the vaccines, it tends to be more common in those aged 16 to 55 years old.

Why are side effects more of an issue with mixed doses?

In a press briefing, lead investigator on the trial Matthew Snape, associate professor in paediatrics and vaccinology at the University of Oxford, said the finding was “intriguing” and not necessarily one they were expecting.

When asked why side effects might be more problematic with mixed doses, he suggested that these reactions often relate to the stimulating of the innate immune response which is your body’s first line of defence.

When you’re exposed to a germ (or a vaccine mimicking infection), your innate immune system kicks in to try and fight it. “These early reactions we’re seeing are more about the innate immune response sending out more of an inflammatory signal,” said Snape.

What are the implications?

Researchers noted that any adverse reactions from mixing doses of the vaccines were “short-lived” and there were no other safety concerns.

But Snape said it’s still important to inform people of these data, especially as mixed-doses schedules are being considered in several countries.

“One of the things it’s telling us is that you wouldn’t want to immunise a ward full of nurses on the same day with a mixed schedule because you may have higher rates of absenteeism the next day,” said Snape.

What about the immune response?

UK researchers hope to report data on how the immune response is impacted by mixing the vaccines in the coming months. “In the meantime, we have adapted the ongoing study to assess whether early and regular use of paracetamol reduces the frequency of these reactions,” added Snape.

Initial results from other countries are looking promising, however. A trial of vaccine mixing in more than 600 people in Spain has found a dose of the AstraZeneca vaccine followed by a dose of the Pfizer jab produces a strong immune response, according to a report in Nature.