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Vaccines Q & A

Q&A: Breakthrough Infections Are Rare But Expected

Recent news that nine vaccinated baseball players for the New York Yankees tested positive for SARS-CoV-2, the virus that causes COVID-19, has thrust the concept of “breakthrough infections” to the forefront of public discourse about U.S. vaccination efforts. William Moss, vaccinology lead for the Coronavirus Resource Center and executive director of the International Vaccine Access Center, discusses the rare but expected presence of breakthrough infections.

William Moss, Executive Director
May 21, 2021

What is a breakthrough infection?

A breakthrough infection is anyone who is considered fully immunized – two weeks after a final vaccination shot – but who subsequently becomes infected with SARS-CoV-2.

Are breakthrough infections expected with vaccines?

The problem in terms of public perception is that people think breakthrough infections mean that vaccines don’t work. That’s certainly not the case. Breakthrough infections are expected because no vaccine is perfect.

How many breakthrough case investigations have there been?

The Centers for Disease Control and Prevention’s Breakthrough Case Investigations and Reporting had been tracking incidents through April 26, 2021, when more than 95 million people had been fully vaccinated in the United States. At that time there were 9,245 reported incidents of breakthrough infections from 46 states, according to the CDC.

‘Breakthrough infections are expected because no vaccine is perfect.’

That is a very, very low rate of 0.01%. There is some undercounting since breakthrough infections can only be counted by states if the infections are detected, and many were asymptomatic like with the New York Yankees players.

The CDC has now switched to tracking only breakthrough infections that have led to serious illness and hospitalizations and deaths. That will generate higher quality data on breakthrough cases.

When would the country need to worry about breakthrough infections?

The red flag indicating that we might have a problem with the current vaccines would be if we start seeing breakthrough infections associated with a special viral variant that was causing hospitalizations and deaths. That would be a trigger for serious concern – and the need for booster doses or modified vaccines.

What are the reasons for breakthrough infections?

It can be very difficult to determine why they occur in an individual person but there are three categories to consider.

First, is it something about the person who got vaccinated? We would expect to see more breakthrough infections in people whose immune systems are compromised by cancer or HIV or immunosuppressive drugs used to treat some conditions.

‘It could be something about the person, the vaccine, or the virus.’

Second, is it something about the vaccine? Different vaccines have different protective efficacies. We’ve seen the highest protective efficacy with the mRNA vaccines and somewhat lower with the adenovirus-vectored vaccines and even lower with inactivated virus vaccines not authorized for use in the U.S. So there are vaccine characteristics that could make it more likely that a breakthrough infection could occur.

In addition, the CDC would want to know whether a cluster of breakthroughs involved vaccines from the same lot to make sure there wasn’t something that happened in the manufacturing pipeline that may have reduced the protective efficacy of that vaccine. We haven’t seen that yet, but that’s something to look out for.

Third, is there something about the virus itself. Of most concern would be whether there are viral variants that may be causing breakthrough infections. For example, the AstraZeneca vaccine seems to provide reduced protection against the B.1.351 variant first identified in South Africa, which opted to no longer use the vaccine.

The most important public health concern is whether there will be variants that emerge that are more likely to cause breakthrough infections, especially if they cause hospitalizations and deaths. That’s the real concern.

Wouldn’t you expect to see breakthrough infections in a group such as a sports team?

It is not surprising that members of the same sports team could experience breakthrough infections. It's basically a mini outbreak among a group of people who are probably in very close contact without masking, without social distancing, and so if they’ve got the virus transmitted among them, that’s going to increase the risk. Plus the team is getting tested far more often than the general public.

The important message is that none of the players got severe disease. Some were actually asymptomatic.

Bottom line is that breakthrough infections are expected but they’re also rare.

William Moss, Executive Director

William Moss, MD, MPH, is Executive Director of the International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health.