Which COVID-19 vaccine has the lowest rate of breakthrough infections?

woman in face mask receiving vaccine
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Unvaccinated people currently account for most new cases of COVID-19 in the U.S., but a small proportion of cases are in vaccinated people; these cases are known as breakthrough infections. But is there a difference in how often people get breakthrough infections depending on which vaccine they got?

The short answer is, we don't know exactly, but there are some hints in the data. The Johnson & Johnson vaccine does seem to have higher rates of breakthrough infection than the Pfizer and Moderna vaccines, but that was expected based on the results of clinical trials. Some very early hints show a slightly lower rate of breakthrough infections with the Moderna vaccine than with the Pfizer vaccine, but that early finding is based on data on a few million people from only two locations and thus may not represent the overall picture in the country.  

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Because no vaccine is 100% effective, breakthrough infections have been expected from the start of the vaccine rollout. In the context of clinical trials, about 0.04% of people given the Pfizer vaccine got infected with SARS-CoV-2, versus about 0.07% with Moderna and 0.59% with Johnson & Johnson. 

Now that the vaccines are authorized, scientists have the chance to track how many breakthrough infections occur in the real-world, beyond clinical trials. When breakthroughs do occur, most people experience mild symptoms, if they fall ill at all, and a small percentage develop severe disease, require hospitalization or die, current data suggests. 

The recent rise of the highly-transmissible delta variant might raise the risk of breakthrough infections, though. For example, a recent Centers for Disease Control and Prevention (CDC) study, published Aug. 6 as a Morbidity and Mortality Weekly Report (MMWR) report, found that the delta variant surged in Mesa County, Colorado between May and June; at the same time, the county accrued a "significantly higher" proportion of breakthrough cases compared with other Colorado counties, where delta was less prevalent. 

Reporting of breakthrough infections now falls largely on the states, and of the 25 or so states that report breakthrough infections, most don't yet provide data on the number of cases linked to each vaccine brand, Live Science found in a search of state health department websites.

However, Oklahoma and Washington, D.C., do make this information public. These data could provide "early signals" regarding how well the vaccines are working, particularly as new variants emerge, the DC Health website states. That said, there are many limitations: The data sets are small, each vaccine was given to different numbers of people and the timing of the doses makes it hard to interpret the data.  

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Still, as of Aug. 1, more than 299,000 D.C. residents had been fully vaccinated, according to data from DC Health. Of these people, nearly 151,000 received the two-dose Pfizer vaccine, about 124,700 got the two-dose Moderna vaccine and about 24,000 received the one-dose Johnson & Johnson vaccine.

In this population, the highest rate of breakthroughs was seen in those who got the Johnson & Johnson shot: 77 people, or 0.32% of the roughly 24,000 recipients. The second highest rate was seen among Pfizer recipients, of whom 308 people, or 0.2%, tested positive for the virus. Finally, 161, or 0.13%, of the Moderna recipients caught a breakthrough infection.

These numbers include asymptomatic, mild, moderate and severe breakthrough cases. Some people with asymptomatic or mild infections may not get tested, so their cases would be missed, meaning this is probably an undercount of breakthroughs.

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Oklahoma has reported similar results. 

As of Aug. 2, more than 1.5 million Oklahomans had been fully vaccinated, according to a report from the Oklahoma State Department of Health. About 817,000 had received Pfizer shots, 674,000 received Moderna and 102,000 got Johnson & Johnson. Again, the Johnson & Johnson recipients showed the highest rate of breakthrough cases, with 215, or 0.21%, testing positive for the virus; 1,468 Pfizer recipients, or 0.17% of the total, caught a breakthrough infection; and 831 Moderna recipients, or 0.12%, tested positive for the virus.

These snapshots from Oklahoma and D.C. likely offer an incomplete picture of breakthrough cases in each region, however, and for now, it's unclear if the observed patterns are representative of the country as a whole. To accurately compare the vaccine brands, particularly with the delta variant still running rampant, we simply need more data, Robert Darnell, a physician scientist at The Rockefeller University in New York, told National Geographic

That said, other preliminary research also suggests Moderna's vaccine offers more protection against the delta variant than Pfizer's, which could help explain the differences in breakthrough rates, Reuters reported. One study, posted Aug. 8 on the preprint database bioRxiv, included more than 50,000 patients in the Mayo Clinic Health System and found that the Moderna vaccine's real-world effectiveness fell from 86% to 76% between January and July, when delta gained prominence. In the same time window, Pfizer's effectiveness fell from 76% to 42%. 

However, that study has not been peer-reviewed yet, so the results still need to be confirmed.

Originally published on Live Science. 

Nicoletta Lanese
Channel Editor, Health

Nicoletta Lanese is the health channel editor at Live Science and was previously a news editor and staff writer at the site. She holds a graduate certificate in science communication from UC Santa Cruz and degrees in neuroscience and dance from the University of Florida. Her work has appeared in The Scientist, Science News, the Mercury News, Mongabay and Stanford Medicine Magazine, among other outlets. Based in NYC, she also remains heavily involved in dance and performs in local choreographers' work.