Within the past week, positive coronavirus test results were delivered to at least three New York Yankees players, an Olympic gymnast alternate, multiple state lawmakers from Texas, a White House official and a staffer in House Speaker Nancy Pelosi's office. They also had this in common: All were fully immunized with coronavirus vaccines, their cases known as breakthrough infections.
The rash of such cases might suggest the coronavirus is regularly blasting by vaccinated people's immune barriers. But these breakthrough infections are not surprising, nor do they suggest vaccines are widely failing.
"Breakthrough infections are to be expected, even when you have highly effective vaccines," said Roy Gulick, chief of infectious disease at Weill Cornell Medicine in New York. To understand why is to understand what vaccines are, and are not, capable of.
This is a dynamic pandemic - scientific understanding of vaccines and the virus continues to evolve, as does the pathogen itself. It is uncertain exactly how rare breakthrough infections are. Ongoing clinical trials, following tens of thousands of vaccinated people for two years, will help determine that rate, said Anthony Fauci, the nation's top infectious-disease doctor, in a Senate hearing this week.
Far more certain, based on clinical trials and real-world data, is that the three vaccines authorized by the Food and Drug Administration broadly protect people from the coronavirus's harmful effects. The vaccines do this so well that doctors refer to them in almost rapturous terms.
"The vaccines are extraordinarily powerful and potent in working to prevent disease," said Robert Darnell, a physician and biochemist at Rockefeller University in New York. "They're incredibly good."
That is not hype. COVID-19, the disease caused by the coronavirus, has become a malady of the unvaccinated.
"If you look at hospitalizations, over 97% of people entering are unvaccinated people," Gulick said. Almost all of the U.S. patients who died recently from COVID-19 were not immunized.
That appears to be true even as delta and other variants of concern spread, though future studies will further clarify how well vaccines stop variants.
"When you hear about a breakthrough infection, that doesn't necessarily mean the vaccine is failing," Fauci said. "It's still holding true, particularly with regard to protection against severe disease leading to hospitalization and deaths."
For now, the data that exist are promising.
Full immunization with the Pfizer-BioNTech vaccine, a two-dose mRNA vaccine, is 88% effective at stopping the delta variant from causing symptoms, according to a study by the U.K. agency Public Health England. The other vaccine that uses mRNA technology, Moderna, probably offers this level of protection too, health experts told the Washington Post earlier this month. Although one study that has not gone through peer review recently found a diminished early response of the single-shot Johnson & Johnson vaccine vs. delta in laboratory tests, other lab studies, such as a New England Journal of Medicine report published in July, indicate a J&J shot can provide a robust response against delta months after injection.
Variants are "roughly represented in the same frequencies" when comparing infections among the vaccinated with those among the unvaccinated, Gulick said, suggesting no variant yet emerged is exceptionally good at breaking through.
But, like all vaccines, the coronavirus shots are imperfect.
A misconception exists that vaccines transform us into totally immune beings, able to instantaneously smite any virus we encounter. Sten Vermund, an infectious-disease epidemiologist and dean of the Yale School of Public Health, likened this false idea to a bug zapper: "As soon as it touches my mucosa or skin or genital tract - boom, zap, it's gone!" Not quite. Instead, Vermund said, vaccines are more similar to poisoned traps, into which a pest might fall, wriggle a bit, then perish from insecticide.
When immunized people are not tested frequently, it is possible many breakthrough infections are dismissed as mild colds or simply go unnoticed. If vaccinated people are tested repeatedly regardless of symptoms, as is the case for Olympians and baseball players, those tests can detect infections before they are defeated by immune systems. Such test results may show snapshots of weakly wriggling virus, to borrow from Vermund's bug-trap analogy. The coronavirus vaccines almost always stop you from getting very sick, but they cannot always stop infection.
Not every infection progresses to COVID-19. It is possible for the virus to exist in someone's nose or mouth without causing the fatigue, aches, loss of smell or other ailments that characterize COVID-19. This is what is known as an asymptomatic infection.
Breakthrough infections can be asymptomatic. They may also involve smaller amounts of virus, emerging data suggest. These infections are likely to be contained in the nose and upper respiratory tract, without harming lungs or other vital organs deeper within the body, according to Tulane University School of Medicine professor and physician Jay Kolls. This, he said, may have to do with how vaccines are delivered.
The coronavirus vaccines provoke the body into making several types of immune fighters, including antibodies that stop the virus from invading healthy cells and T cells that hunt and kill infected cells. Coronavirus shots are frequently given in arm muscles, and as a result these defenders are generated in nodes and organs nearby in the chest. A few days after a virus invades, those disease fighters can be summoned to the infection site to thwart the virus.
One type of antibody secreted in mucus membranes guards where the coronavirus enters in the nose and mouth, Kolls said. He hypothesizes that vaccines delivered through the nose - about half-a-dozen are in clinical trials - may be even better at preventing infection because they could stimulate and sustain antibody production right in the nasal cavity.
There is precedent for targeting the site where a pathogen enters. The first polio vaccine, which successfully stopped illness, was injected into muscle like the coronavirus vaccine is. But the oral polio vaccine developed a few years later more successfully prevented infection by blocking the poliovirus from infiltrating through the gut. This, for decades, was the go-to polio vaccine in the United States, until it was replaced by a refined version of the injected polio vaccine. That vaccine and the oral vaccine work equally well at preventing polio, according to the Centers for Disease Control and Prevention.
Estimating the total number of coronavirus breakthrough infections is difficult. Through the end of April, the CDC reported slightly more than 10,000 cases among 101 million fully vaccinated adults, which is about 1 case per 10,000 vaccinated people. But this is probably an undercount, CDC scientists said, because of its reliance on voluntary reports. It also reflects a time when the highly transmissible delta variant of the coronavirus was not yet in wide circulation in the United States.
It is clearer that severe breakthrough cases are extremely rare. Fewer than 5,500 hospitalizations and deaths among vaccinated people had been reported to the CDC as of July 12. The CDC has, since May, ceased reporting asymptomatic or mild breakthrough cases.
Vermund and two other researchers, in an editorial in the Journal of the American Medical Association, recently called on the CDC to revive its surveillance of symptomatic breakthrough infections, even if those cases are not severe enough to cause hospitalization or death. This, Vermund said, could offer persuasive data to inspire confidence among the vaccine-hesitant and help track transmission among vaccinated people.
In a statement Friday, the CDC said it has several ways to investigate breakthrough cases, including in coordination with state and territorial health departments. The agency said that as more people are vaccinated, more breakthrough cases are expected.
Tracking vaccinated people via frequent screening can offer insight into the rate of breakthroughs. National Institutes of Health director Francis Collins, in a Washington Post Live appearance this week, said NIH has seen "an occasional breakthrough" among its 46,000 employees, most of whom are immunized.
"Those people aren't very sick. They have mild symptoms. We have yet to see anybody really get in trouble," Collins said.
At Rockefeller University, where faculty and staff are regularly tested, two out of more than 400 vaccinated employees had breakthrough infections, according to a recent report in the New England Journal of Medicine by Darnell and his colleagues.
The two employees developed what Darnell called "pretty classic COVID-19 cases," which included the loss of sense of smell and taste. Although one woman had high viral levels in her saliva, neither progressed to "hospital grade" COVID. In fact, Darnell said both patients would have been fine without seeing a doctor.
Whether the breakthrough infection that involves symptoms could result in long COVID remains unknown.
"We're in a data-free zone here," said Steven Deeks, an infectious-disease physician at the University of California, San Francisco who studies COVID-19's long-term effects. "We have no idea - none whatsoever - as to whether breakthrough infections will cause PASC," he said, referring to post-acute sequelae of COVID-19, the clinical name for long COVID.
Deeks hypothesizes that long COVID depends, in part, on the amount of virus present in the early stage of infection.
"One hopes that the virus load in people with breakthrough infections will generally be lower," Deeks said. That, in turn, could mean a lower risk for developing long COVID.