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Mixing COVID Vaccine Brands Appears Safe, But More Likely to Cause Side Effects

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Key Takeaways

  • Using two different COVID-19 vaccines for first and second doses is more likely to lead to side effects, according to preliminary study results.
  • The reactions after the second dose were the same as those commonly seen after getting the same vaccine for both shots—fever, chills, fatigue, and headache.
  • The study only reported on the reaction profile for using different vaccines, not whether effectiveness changes. A report on the effectiveness of mixed doses of vaccine will be released in a few weeks.

If your first COVID-19 vaccine dose was Pfizer and your second dose was Moderna, what would happen? New research is investigating the risks of combining different COVID-19 shots in an attempt to answer that question.

The British study, however, involved a brand not yet authorized for use in the U.S.: AstraZeneca/Oxford. The other brand used in the study was Pfizer/BioNTech, which is authorized in America.

“The driver behind this study was to see if it's going to be appropriate to mix and match different vaccines,” Matthew Snape, MD, associate professor in pediatrics and vaccinology at the University of Oxford said during a video briefing about the study. He explained that being able to use a different vaccine for the second shot would build “flexibility and resilience” into vaccine programs around the world facing shortages and supply issues.

This mix-and-match approach is called heterologous dosing. And while it makes the standard COVID-19 vaccine side effects more common, it doesn't seem to make them worse or present any safety concerns.

More Reactions, But Mild to Moderate

The reactions study participants experienced were the same as those frequently documented after any of the SARS-CoV-2 vaccines: fever, chills, fatigue, and headache. Symptoms did not last long and were usually managed with acetaminophen. No one in the study was hospitalized due to reactions.

Thirty-four percent of participants who received AstraZeneca first and Pfizer second reported side effects, compared to 10% of people who received two doses of the AstraZeneca vaccine. Fever was reported by 41% of the people who received Pfizer first and AstraZeneca second, compared to 21% of the those given two doses of the Pfizer vaccine.

Snape suggested that a vaccination program for healthcare workers should take the more frequent occurrence of reactions into account if heterologous dosing is used. Vaccinating everyone in a health facility at the same time could mean simultaneous work absences due to the reactions, he notes.

The study is part of the Oxford Vaccine Group’s ComCov trial to examine different combinations of COVID-19 vaccines. This part of the trial only evaluated the types and severity of reactions to the vaccinations. A report on the effectiveness of using different vaccines is expected in a few weeks.

In this study, 830 volunteers were randomly assigned to one of four vaccine protocols:

  • The first group received the AstraZeneca vaccine with shots spaced 28 days apart
  • The second group received the Pfizer vaccine with shots spaced 28 days apart
  • The third group received the AstraZeneca vaccine first and the Pfizer vaccine second
  • The fourth group received the Pfizer vaccine first and the AstraZeneca vaccine second

Reactions May Be a Good Thing

It may be good news that the reactions following the second heterologous dose of vaccines are more frequent. According to Chris Beyrer, MD, MPH, the Desmond M. Tutu professor in Public Health and Human Rights at Johns Hopkins Bloomberg School of Public Health, a stronger reaction to a vaccine may indicate a more robust immune response. This bodes well for defending against the SARS-CoV-2 virus.

“That is encouraging, although it is uncomfortable,” Beyer tells Verywell.

Using two different vaccines could provide greater effectiveness because they work in different ways, Beyrer says. The Pfizer vaccine, which is a messenger RNA vaccine, stimulates the production of antibodies. Antibodies are small proteins that can neutralize a virus.

On the other hand, the AstraZeneca vaccine uses an altered adenovirus (an inactivated strain of the common cold) to stimulate the production of T cells. T cells identify viral proteins, bind to them, and kill the virus.

However, the effectiveness of a heterologous dosing pattern remains to be seen.

Being able to use different brands or types of COVID-19 vaccine will be useful if booster shots are needed in the future, either to maintain immune response or to provide immunity to variants of the SARS-CoV-2 virus.

“[The virus] has shown an ability to mutate. It has generated more infectious variants and some more pathological variants,” Beyrer says. A future booster shot to protect against these variants may not have to match the original shot you received, he explains.

To Beyrer's knowledge, no one in the United States has received different doses of vaccine. Supplies of vaccine have been steady. But the ongoing surge of COVID-19 in India has interfered with supplies globally, since India is a major hub of vaccine production.

What This Means For You

Mixing and matching COVID-19 vaccine brands for the first and second dose could give vaccination programs around the world more flexibility, since vaccines are in short supply in many countries. Reactions may be more frequent, but are mild in severity.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

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  1. Shaw RH, Stuart A, Greenland M, Liu X, Van-Tam JSN, Snape MD. Heterologous prime-boost COVID-19 vaccination: initial reactogenicity dataThe Lancet. Published online May 2021:S0140673621011156. doi:10.1016/S0140-6736(21)01115-6