The recent headlines have been alarming: “2% of COVID Deaths in Illinois This Year Have Been Fully Vaccinated Residents.” “El Paso records over 200 COVID-19 vaccine breakthrough cases.” “79 fully vaccinated Massachusetts residents have died.”
At a time when Covid-19 cases are rising again in the US and the more dangerous delta variant of the virus behind the disease is gaining ground, seeing that vaccines are not a perfect shield can be disheartening. With vaccination rates slowing, reports of people becoming infected after their immunizations could feed vaccine hesitancy, which in turn can fuel more breakthrough cases.
But despite these emerging reports of breakthrough infections, the fact remains that vaccines are the most effective tool for containing Covid-19, and they have proven to be excellent at preventing people from getting severely ill or dying of the disease. Even as new, more slippery variants of the coronavirus have emerged, most of the vaccines have held their ground.
As such, being unvaccinated is the most dangerous position to be in during the pandemic. “Preliminary data from a collection of states over the last six months suggests 99.5 percent of deaths from Covid-19 in these states have occurred in unvaccinated people,” Centers for Disease Control and Prevention Director Rochelle Walensky said during a July briefing.
At the same time, it’s clear that vaccines are not impregnable. As more people have become immunized against Covid-19, the number of breakthrough infections — cases of people getting infected after getting their shots — has gone up. That’s not a surprise.
“Vaccine breakthrough cases are expected,” according to the CDC.
That’s because no vaccine is 100 percent effective at blocking an infection in all circumstances. And while Covid-19 cases declined rapidly from their peak as vaccinations increased, the SARS-CoV-2 virus that causes the disease is still wreaking havoc. There are still people vulnerable to infection among those who are vaccinated, which is a recipe for occasional breakthrough infections.
The tiny fraction of breakthrough cases that have arisen show how amazingly effective Covid-19 vaccines have been at defanging and declawing a devastating disease. But they also show that when vaccination rates are low, Covid-19 is a greater threat now than it has ever been. That poses a challenge for vaccinated people who want to resume their normal lives but also take steps to curb the spread of the disease.
It’s important to first clarify what a breakthrough infection actually means.
The CDC definition of a breakthrough infection is a laboratory-confirmed infection more than 14 days after the final dose of a Covid-19 vaccine, as it can take a while for the full protection of a vaccine to spool up. This definition includes everything from infections that produce no symptoms at all to cases that result in death. “People often think about ‘infection’ and ‘disease’ as being the same thing, and that is not the case,” said Brianne Barker, a virologist at Drew University.
It’s only when a virus starts causing symptoms that an infected person is said to have disease, so not all SARS-CoV-2 infections cause Covid-19. But as we’ve seen throughout the pandemic, people can carry and transmit the virus without falling ill themselves, creating a major route for the spread of Covid-19. That’s why tracking breakthrough cases is so important.
“Breakthrough infections are not unique to COVID-19, but we are indeed noticing and talking more about breakthrough infections because we are testing people frequently [for Covid-19 rather than other diseases], even those fully vaccinated, and therefore finding and tracking these cases more closely,” said Paulo Verardi, a virologist at the University of Connecticut, in an email.
The Covid-19 vaccines that have been distributed in the US — Johnson & Johnson, Moderna, and Pfizer/BioNTech — were all evaluated based on how well they prevented disease, not infection. Even with a vaccine like Moderna’s, which demonstrated close to 95 percent efficacy against disease in clinical trials, a fraction of recipients still fell ill after getting their shots.
The bulk of evidence does show that Covid-19 vaccines slow transmission alongside reducing deaths and hospitalizations, but they don’t halt the spread completely.
Taken together, these factors mean that even in the most ideal scenario with everyone vaccinated against Covid-19, there will still be a segment of people who can contract, spread, and succumb to the virus. But the more people who get vaccinated, the harder it is for the virus to find a vulnerable host. Even people with incomplete protection are effectively shielded. This is the idea behind herd immunity. So a key tactic to reduce infections among those who are vaccinated is more vaccination.
There are indeed people who face a greater risk of getting a breakthrough infection.
For example, people who have received organ transplants may be on immunosuppressant drugs that can interfere with how well a vaccine can protect against a disease. Others may have genetic factors that make it harder for them to mount an immune response to the virus even post-vaccination. In some cases, a breakthrough infection is just bad luck.
And many of the same risk factors for severe illness from Covid-19 still apply when people are vaccinated. A study of 152 breakthrough infections causing hospitalizations in Israel found that just 6 percent had no underlying health conditions. The rest had conditions ranging from high blood pressure to diabetes to cancer.
A preprint study that has not yet been peer-reviewed looked at 2,394 breakthrough infections in the United Kingdom and found that older adults, particularly those living in impoverished areas, were at greater risk of getting infected after their injections. Scientists have long established that the immune system declines with age. The authors did observe that infections among those who are vaccinated were far milder than in unvaccinated people.
There are around 52 million Americans over the age of 65. Sixty percent of all Americans have at least one chronic condition, and 40 percent have more than one. That means a large swath of the population may have diminished protection from a vaccine. But vaccines still drastically reduce the risk of disease and hospitalization from Covid-19, even among people in high-risk groups.
As of July 6, the CDC reported 5,186 cases of breakthrough Covid-19 cases that led to deaths or hospitalizations among 157 million fully vaccinated people in the US. That’s about a 0.003 percent breakthrough rate for severe disease, although the CDC acknowledged that this is likely an undercount, since the numbers are drawn from voluntary reports and patchy surveillance. Of the 5,186 severe illnesses, 4,909 were hospitalizations and 988 led to death. So breakthrough infections are rare, even among people who are more vulnerable.
Compare that with the state of the pandemic in December before vaccines were widespread: 6.3 million new infections, 123,000 hospitalizations, and more than 65,000 deaths from Covid-19 were recorded that month. Even with less than half the US population currently vaccinated, Covid-19 vaccines have helped cause a huge drop in cases.
Vaccines work by giving the immune system a target to practice against so that when a pathogen does strike, the immune system can hold it off without causing an illness.
With most Covid-19 vaccines, the target is the spike protein of the SARS-CoV-2 virus. This is the part of the virus that actually attaches to human cells to begin the infection process, so coaching the immune system to identify it and block it off can prevent the virus from doing damage.
The trouble is that everyone’s immune system doesn’t respond the same way to a vaccine, and the virus itself is mutating. So a breakthrough infection may occur “because the immune response is too low or is not high in the right anatomic location, or it could mean that the virus has changed so the target that the immune system recognizes is no longer the same,” said Barker, the Drew University virologist.
Right now, it’s hard to gauge whether someone who received a Covid-19 vaccine is adequately protected. The specific combination of the immune system’s T cells, B cells, and antibodies that shield against the virus is known as the correlate of protection or correlate of immunity. Researchers are still trying to figure out exactly what those benchmarks are, which could allow them to figure out who remains vulnerable after getting their injections. Early evidence shows that antibody levels can predict how well an individual is protected, but antibodies are not the whole story when it comes to immunity.
It’s also not clear whether breakthrough infections can cause long-term symptoms at the same rates as Covid-19 in unvaccinated people. The phenomenon of long Covid or Covid long-haulers remains an enduring mystery of the pandemic.
Many of the SARS-CoV-2 variants like delta have mutations in the spike protein, rendering some vaccines less effective at preventing infections. These mutations help delta evade the immune system, infect cells more easily, and spread more readily among people. The more variants like this spread, the more breakthrough infections are expected.
Coupled with persistent holdouts against vaccinations and people who have yet to receive them, variants are a major public health concern.
“At an individual level, the vaccines are highly effective, and people who have been vaccinated should not be worried for themselves necessarily getting Covid,” said Karen Jacobson, an infectious disease researcher at the Stanford University School of Medicine. “The concern that a lot of people have started to express recently, especially with the new variants, is more on a population level, and the fact that we have large pockets of the population [who] are not vaccinated.”
With variants circulating readily among unvaccinated people, the chances of an elusive strain infecting someone who has been immunized rises. And as the virus spreads, it accumulates more mutations, increasing the chances of an even more dangerous variant emerging.
The circumstances that lead to breakthrough infections are largely the same as they are for infections in people without protection. Some of the highest-risk settings for exposure are crowded indoor gatherings in poorly ventilated spaces, like for workers in health care settings. But large gatherings in general can still be a venue for causing breakthrough infections, as dozens of vaccinated tourists visiting Provincetown, Massachusetts, discovered earlier in July when they tested positive for the virus.
However, the risk is not spread evenly across the country. In the United States, nearly half of all residents and close to 60 percent of adults have been vaccinated as of July 14. Yet there are places where less than one-third of people have been vaccinated. The chances of breakthrough infections tend to be highest in areas where Covid-19 cases remain high and vaccination rates remain low.
Recently, the US has experienced an uptick in hospitalizations and deaths from Covid-19 after months of decline. The rise is due mainly to case increases in parts of states like Texas, Missouri, and Nevada that have low vaccination rates and are seeing more instances of the delta variant. But many of these regions are relaxing all their restrictions around Covid-19 and allowing life to resume as normal, despite the ongoing transmission of the virus.
These fissures in the pandemic are poised to grow. Getting people to act to limit the spread of the virus is only getting harder as fatigue takes hold. The result is that even more people who are vaccinated may end up infected, prolonging the spread of SARS-CoV-2 and slowing the drawdown of the Covid-19 crisis.
One of the challenges with understanding how to deal with breakthrough infections is that the term encompasses several different outcomes, and they aren’t tracked easily.
The disease cases are the most worrying from a public health perspective and the easiest to monitor, but asymptomatic infections and transmission are also concerning because they mean the virus is still replicating, mutating, and spreading even among vaccinated people. While individuals gain robust protection from vaccines, if the overall vaccination rate is low in a population, even immunized people can become part of the chain of transmission.
In the US, testing for Covid-19 has declined, especially among people who have been vaccinated, so it’s hard to figure out just how much immunized people are spreading the disease unwittingly. The CDC said in May that it would stop trying to track asymptomatic breakthrough infections and would investigate only hospitalizations and deaths.
Breakthrough infections that do cause symptoms tend to be mild, so many vaccinated people who experience a cough, runny nose, or fever are not bothering to get tested for Covid-19. That makes it even harder to keep tabs on the spread of the virus.
“Certainly we could be missing cases, and I think continuing to have surveillance even in vaccinated populations is really important, especially if we’re talking about variants,” said Jacobson.
At the same time, the US is still struggling to sequence enough genomes of the viruses that are found. Genome sequencing is critical for both identifying which variants of SARS-CoV-2 are circulating and finding new mutations as they emerge. Without adequate sequencing, new, more dangerous variants can spread undetected.
It’s hard to come up with a strategy to deal with a problem that’s so alarming yet so rare. But in general, the same tactics deployed throughout the Covid-19 pandemic still work at preventing breakthrough infections.
The best strategy for preventing breakthrough infections is increasing vaccination rates further, getting to the point where enough people are immunized to prevent SARS-CoV-2 from jumping person to person easily. The added benefit of vaccinations is that they also reduce opportunities for mutation.
After that, precautions against Covid-19 like social distancing and wearing face masks may still be needed in some circumstances, like in places where cases are rising. “At this point with the Delta variant on the rise we cannot let our guard down and must still be vigilant when in public spaces, particularly crowded indoor spaces,” said Verardi, the University of Connecticut virologist. “As for me, I don’t plan on letting go of my mask when I’m in such spaces, at least for the time being.”
And as the virus continues evolving, it may change in ways that render vaccines much less effective. Companies are already developing booster shots to better target SARS-CoV-2 variants and bolster immunity, but whether they will be needed is still unclear.
However, there’s a lot we don’t know about how the vaccines will hold up over time, and the Covid-19 pandemic may still have more surprises in store. Protection from the vaccines still seems strong months after the doses are administered, and the immune responses they generate are in line with those produced by some of the best-known vaccines, indicating that the immunity they confer will likely last a long time.
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