Moderna Vaccine May Lead to Fewer Breakthrough Infections Compared to Pfizer

vial of moderna booster vaccine with super hero cape

Jessica Olah / Verywell

Key Takeaways

  • A recent study shows that recipients of the Moderna COVID-19 vaccine had a lower risk of breakthrough infections and hospitalizations than people who received the Pfizer vaccine.
  • More research is needed to understand the reasons behind this difference in risk.
  • The overall risk of breakthrough infections is low.

COVID-19 vaccines are highly effective at preventing serious illness and death, but they cannot eliminate the risk of infection completely. This means that vaccine breakthrough infections—which occur when someone who is fully vaccinated becomes infected—are to be expected.

However, according to a recent study published in JAMA, the risk for breakthrough infections varied depending on what shot you received. The recipients of the Moderna COVID-19 vaccine had a lower risk of breakthrough infections and hospitalizations than the recipients of the Pfizer vaccine.

The researchers analyzed the electronic health records of more than 637,000 fully vaccinated patients and studied breakthrough infections that occurred between July and November 2021, the period when Delta was the predominant variant circulating in the U.S.

By November 2021, the monthly rate of breakthrough infections among recipients of the Pfizer vaccine reached 2.8 cases per 1,000 persons, compared to 1.6 cases for Moderna.

More research is needed to understand the reasons behind this risk and how these results hold up against the Omicron variant.

Why Is the Risk of Breakthrough Infections Different?

The study did not dive into why there was a difference in risk between the two vaccines.

“It is difficult to make direct comparisons from observational data since there could many confounders that may not have been measured in the analysis,” Shobha Swaminathan, MD, associate professor of medicine at Rutgers University, and medical director of the infectious diseases practice at University Hospital, told Verywell. “The vaccines are also slightly different.”

The vaccines are not exactly the same, so it makes sense that their risk of breakthrough infections wouldn’t be the same either. Currently, experts can only speculate why people who received the Pfizer vaccine appear to have a higher risk.

For instance, the Moderna vaccine has 100 micrograms of mRNA, while the Pfizer vaccine contains 30 micrograms, which may play a role. While the former is administered 28 days apart, the latter only requires an interval of 21 days. The dosing interval may be crucial since a 2021 study published in Cell found that antibody levels were much higher when the dosing interval of the Pfizer vaccine was extended to six to 14 weeks.

Some experts speculate whether Pfizer patients simply got vaccinated before those who received Moderna shots. The Pfizer vaccine was authorized a few weeks before Moderna. Vaccine protection wanes over time, so those who got vaccinated earlier may be more vulnerable to breakthrough infections. But that’s likely not the case in this study.

“When we’re comparing infections and outcomes between recipients of these two vaccines, we have taken into account patient characteristics and varying timing of vaccination,” Rong Xu, PhD, study author and director of the Center for Artificial Intelligence in Drug Discovery at the Case Western Reserve University, told Verywell.

Although the risk of breakthrough infections is generally low, rates may also vary depending on an individual’s underlying health conditions. “Our data show that the rate of breakthrough infections in patients with blood cancer, colorectal cancer, or lung cancer can be quite substantial,” Xu added.

What This Means For You

The risk of breakthrough infections and hospitalization may be slightly higher for people who got the Pfizer vaccine, but the vaccine remains highly protective against severe illness and death. Overall, the risk of COVID-19 infections remains much higher for unvaccinated people than vaccinated individuals.

If You Got Pfizer, Should You Be Worried?

Breakthrough infections are generally uncommon no matter which mRNA vaccine you received.

“While the difference between the two vaccines is statistically significant, they are not markedly different,” Xu said. “The overall risks for breakthrough infections and hospitalizations in recipients of both vaccines are low.”

If you’re fully vaccinated and you got COVID-19, you are still less likely to develop serious illness than unvaccinated individuals who get infected.

“I think that despite the differences, both vaccines were extremely effective in reducing hospitalizations and both vaccines were equally effective in preventing deaths from COVID-19,” Swaminathan said.

Based on the data, there was no significant difference observed in the mortality rates between the recipients of the two vaccines. Although the risk of breakthrough infections is never zero, it’s important to remember that the vaccines remain highly effective at what they are meant to do: provide protection against the most severe consequences of COVID-19.

What About the Omicron Variant?

It’s possible that the risk of breakthrough infections is higher with the Omicron variant, but we need more data to be certain.

“The Omicron variant is quite different from the original virus and therefore is able to cause more infections,” Swaminathan said. “However, it seems clear that while we are seeing breakthrough infections, the majority of the infections remain mild and rates of hospitalizations, ICU admissions, and deaths among those who have been vaccinated and boosted remain extremely low.”

The researchers studied the cases of breakthrough infections during the Delta period, but Omicron is now the predominant variant. We have yet to see if there is also a significant difference in the risk of breakthrough infections and hospitalizations between the two mRNA vaccines.

“We are currently working on comparing these vaccines on Omicron-associated infections and outcomes,” Xu said.

The risk of breakthrough infections is low overall, but to err on the side of caution, experts recommend you keep taking precautions.

“It still goes back to the basics of masking in public areas when indoors, frequent hand hygiene, and making sure that you and those around you have been vaccinated and received the booster dose,” Swaminathan said.

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.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Wang L, Davis PB, Kaelber DC, Volkow ND, Xu R. Comparison of mRNA-1273 and BNT162b2 vaccines on breakthrough SARS-CoV-2 infections, hospitalizations, and death during the Delta-predominant period. JAMA. Published online January 20, 2022. doi:10.1001/jama.2022.0210

  2. Centers for Disease Control and Prevention. Interim clinical considerations for use of COVID-19 vaccines currently approved or authorized in the United States.

  3. Payne RP, Longet S, Austin JA, et al. Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine. Cell. 2021;184(23):5699-5714. doi:10.1016/j.cell.2021.10.011

  4. Centers for Disease Control and Prevention. The possibility of COVID-19 after vaccination: breakthrough infections.

By Carla Delgado
Carla M. Delgado is a health and culture writer based in the Philippines.