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May 13, 2021, 3:59 p.m. EDT

Mixing Pfizer and AstraZeneca COVID-19 vaccines increases mild side effects but is safe, study shows

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By Lina Saigol

Mixing doses of COVID-19 vaccines increases the risk of mild to moderate side effects when compared with administering two shots of the same vaccine, but is safe, according to data from a key U.K. trial.

The  Com-Cov study, led by the University of Oxford, was launched in February to compare the effect of administering a first dose of the vaccine developed by Oxford and drug company AstraZeneca /zigman2/quotes/200304487/composite AZN +0.03% /zigman2/quotes/203048482/delayed UK:AZN +0.01% followed a few weeks later by the vaccine made jointly by drug company Pfizer /zigman2/quotes/202877789/composite PFE -1.70%  and its partner BioNTech /zigman2/quotes/214419716/composite BNTX -0.83% , and vice versa.

The trial involved 830 volunteers aged over 50, who received four different combinations of the AstraZeneca and Pfizer–BioNTech shots. The first full results are expected to be published in June.

Preliminary results, published on Wednesday in a peer-reviewed letter in medical journal The Lancet , showed that participants receiving a mixed schedule of the vaccines incurred more frequent reactions, such as chills, fatigue, headache, and muscle pain, than those on standard nonmixed schedules.

For example, 34% of people who received an AstraZeneca shot followed by a Pfizer–BioNTech one felt feverish, compared with 10% of those who received two doses of the AstraZeneca vaccine.

However, any adverse reactions were short-lived, with no other safety concerns, the researchers wrote.

Read: EU won’t renew AstraZeneca COVID-19 vaccine; Pfizer shot will take precedence

The results will be closely watched by several countries that are considering mixing COVID-19 vaccines in immunization campaigns, either because of safety concerns about the AstraZeneca shot following reports of blood clots in some recipients, or to help shore up supplies.

The Canadian provinces of Ontario and Quebec have both said it is likely that recipients of the AstraZeneca vaccine may receive a different shot for their second dose. Meanwhile, the U.K., France and Germany are all offering a second dose of a different vaccine to younger people who received a first dose of the AstraZeneca shot, following concerns over rare blood clots in some recipients of the shot.

Read: Under-40s to be offered alternative COVID-19 vaccines to AstraZeneca’s

Matthew Snape, associate professor in pediatrics and vaccinology at the University of Oxford, and chief investigator on the Com-Cov 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 immunization, and this is important to consider when planning immunization of healthcare workers.

“Importantly, there are no safety concerns or signals, and this does not tell us if the immune response will be affected,” Snape said.

The researchers also cautioned that the side effects of mixing vaccines could be worse for younger people, who tend to have more active immune responses than participants in the study who were aged 50 and above.

Read: Moderna and Novavax added to ‘mix and match’ COVID-19 vaccine trial

In April, the trial was expanded to include the COVID-19 vaccines made by biotech Moderna /zigman2/quotes/205619834/composite MRNA -1.62% and vaccine developer Novavax /zigman2/quotes/202614340/composite NVAX -3.05% . The new study — called Com-Cov 2 , seeks to recruit adults aged over 50 who have received their first vaccination in the past eight to 12 weeks, bringing the total number of participants in the trial to 1,050.

Volunteers would have received either the AstraZeneca or the Pfizer–BioNTech vaccine, and then be randomly allocated to receive either the same vaccine for their second dose or a dose of the vaccines produced by Moderna or Novavax. The trial is designed as a so-called ‘noninferiority’ study, which means its intent is to demonstrate that mixing isn’t substantially worse than not mixing.

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