Are the stories of “breakthrough infections” as scary as they sound? What are COVID symptoms like if you’ve been double-jabbed? And what do these cases mean for reopening?
On America’s Fourth of July weekend this year, the summer beyond the pandemic seemed just over the horizon. Almost 60 per cent of Americans were fully vaccinated against COVID, mask mandates had been thrown out around most of the country, and in Massachusetts, thousands of tourists descended on Cape Cod as they had before the pandemic, to celebrate after a long winter. But the highly contagious Delta variant was already loose there and, within days, hundreds of people were infected.
Nearly three-quarters of them were fully vaccinated.
The vaccines seemed to still be doing their job at preventing severe disease (no one died in a 469-strong cluster at Cape Cod and just four vaccinated people were hospitalised) but the double-jabbed appeared to be shedding just as much virus as those who weren’t. That prompted the Centers for Disease Control and Prevention (CDC) to again recommend masks for everyone, vaccinated or not, in public indoor places.
So how serious are these so-called “breakthrough infections” – and what do they mean for the freedoms we hope a more vaccinated world will bring?
I thought vaccines stopped COVID. Why are some people still getting infected?
While we generally think of vaccines as stopping infection outright, they are actually designed, first and foremost, to help you survive an infection.Advertisement
Some shots are better than others at their second job – that is, stopping you from catching and so spreading the virus on to others, thereby building up herd immunity in the population and slowing the spread of the pathogen. The vaccine against the human papillomavirus (HPV) is very good at this, for example.
But infections can still “break through” among the vaccinated after common shots for influenza, measles and many other illnesses. Officially, a breakthrough infection is when you have caught the virus at least two weeks after your two doses, when your full immunity should have kicked in.
As the world battles the better-evolved Delta variant of COVID, breakthrough infections have hit places such as the US and Israel harder than expected, making some experts wonder if we can achieve herd immunity through vaccination after all. But data on the ground suggests that the shots are still doing very well at their first job – stopping most severe disease. “It’s still close to 100 per cent protection from death,” says infectious disease physician Associate Professor Paul Griffin.
A recent US study found that an unvaccinated person was 29 times more likely to end up in hospital from COVID than someone who was vaccinated. In Australia, that trend has followed;almost all the COVID patients in hospital during the nation’s latest Delta outbreak aren’t vaccinated.
Breakthroughs don’t mean the vaccines aren’t working, says biostatistics professor Ian Marschner at the University of Sydney’s NHMRC Clinical Trials Centre. Sometimes, with asymptomatic cases, it can even be a sign they are.
Vaccines give you a harmless piece of the virus dressed up to look dangerous in order to trick your immune system into making the antibodies and killer T-cells needed to fight off the virus – these immune defenders will then remember how to eliminate the virus if it ever shows up for real. Think of your immune system as a cop on patrol. The vaccine gives it a mug shot of the viral invader to watch out for, so it can hunt it down fast. But it doesn’t lock the gate to stop it from coming in altogether.
That’s why very few vaccines get close to achieving what is known as “sterilising immunity”, the kind the HPV vaccine gives, where a pathogen is stopped in its tracks almost the moment it enters your body.
Still, in many cases, the vaccine works so well a person will never even know the virus got into their system. But if they took a test they might well test positive. Others might still get mild symptoms over a shorter duration as the virus is defeated.
But in rarer cases, Griffin says, someone’s immune response might not be where it needs to be after the vaccine because, say, they have a weakened immune system from cancer treatment or an autoimmune condition. Or, the dose of virus they are hit with – just like for an infection in an unvaccinated person – might be particularly high, overwhelming their immune defences. That could explain why a small number of vaccinated healthcare workers wearing protective gear have been infected. They’ve been exposed to lots of virus for a longer time.
A US study found that when vaccinated frontline workers fell ill, their sickness lasted about six days less than those unvaccinated.
Achieving sterilising immunity is notoriously difficult to do with respiratory illnesses in particular, the ones that take hold where the virus enters your body – the nose and mouth, says Griffin, who has been involved in COVID vaccine trials throughout the pandemic. While there are special kinds of antibodies that coat the nose and throat, they generally don’t hang around as long as we’d like (research is ongoing into developing nasal spray vaccines for COVID that would deliver the immunity hit closer to the battleground, but right now the shot in the arm still works best).
“We see this challenge with the flu shot every year,” Griffin says. “Of course, that’s a lot less effective than the new COVID vaccines. These new ones are safe and they’re better than a lot of vaccines we already have.”
How many breakthrough infections are we seeing?
Countries generally don’t monitor breakthrough infections specifically in their caseload data, so it’s hard to say exactly how common they are, but experts say they do not appear to happen nearly as often as after our seasonal influenza vaccines. On July 30, fewer than 1 per cent of fully vaccinated people in the US reported breakthrough COVID infections, based on the data of the 25 states tracking them, for example. The CDC there monitors breakthrough cases that end up in hospital, as do Australian authorities. On August 30, more than 173 million Americans were fully vaccinated and during that time the CDC reported 12,908 patients had been hospitalised or died with breakthrough infections. A study of about 11,000 fully vaccinated healthcare workers in Israel found just 39 were infected out of 1497 who developed suspicious symptoms or exposure to COVID.
That study was during the surge of the Alpha variant, not Delta. People infected with the “game-changing” Delta shed even more virus – meaning they tend to pass on a higher dose to those around them. That could explain why places such as the US and Israel are starting to see more breakthrough infections, experts say. But it could also be simple maths: more people in the total population are now vaccinated. As biostatistics professor Ian Marschner at the University of Sydney’s NHMRC Clinical Trials Centre explains, “if a country has a 100 per cent vaccination rate then 100 per cent of infections will come from vaccinated people”.
The world’s COVID vaccination campaign is not only the largest and the fastest in history, it’s also being monitored more closely than any before it. That means even the rarest complications (such as blood clotting linked to the AstraZeneca jab and heart inflammation in some receiving Pfizer) are being picked up. “And we’re better at diagnosing the infection, including breakthroughs than we have been for past viruses too,” Griffin says. “Meanwhile, it’s hard to quantify all the cases the vaccines have stopped, all the lives saved.”
As vaccination continues to gather pace, experts warn a new paradox will emerge – more vaccinated people will get infected than unvaccinated. To make sense of it, Griffin suggests thinking of vaccines as seatbelts. “Most car crashes involve people who are wearing them. But that doesn’t mean the seat belts aren’t working. We know they still give us much better outcomes when we do crash compared to people not wearing them, but seatbelts can’t stop the car crashing altogether.”
Vaccinated people are also now the ones more likely to be exposed to the virus, he says, already exempt from lockdown rules in many countries. “Places like Israel, they’ve allowed vaccinated people more freedoms, and, while that’s clearly the right thing to do, those people then moved around more, perhaps use fewer other mitigation strategies like masks and hand hygiene. So even when we get those higher vaccine rates, we need to be mindful of that. We can’t get too complacent.”
How bad can breakthrough infections be?
Israel may be the poster child of high vaccination coverage during this pandemic but, after dropping restrictions and reopening, its latest surge in cases has made it a cautionary tale too. With about 60 per cent of people hospitalised with the coronavirus also fully vaccinated, it’s now become a favourite case study for those who claim the vaccines don’t really protect us against the ravages of COVID. But there’s another key statistic missing from that analysis: Israel’s vaccinated population is now almost everyone, more than 80 per cent are immunised over 12 years old. When you look instead at the rate of hospitalisation in the vaccinated against those still unvaccinated, University of Pennsylvania biostatistician Jeffrey Morris explains, that number reverses: the unvaccinated are hospitalised three and a half times as often.
Griffin says that, while people can still get sick with breakthrough infections, they usually have fewer and less severe symptoms and recover faster. An April studyof almost 4000 frontline workers in the US found that vaccinated people who fell ill had a 58 per cent lower risk of fever and reported two fewer sick days in bed. On average, their illness lasted six days less than those who weren’t vaccinated.
“There will always be that one unlucky person who does everything right and gets sick.”Dr Paul Griffin
“Just like our flu vaccines, all these vaccines [generally] keep you out of hospital,” Griffin says. “You can see that in our ICU numbers here, very few people have been double-dosed. So, it really does alter the course of the infection.”
Often people who die of breakthrough infections have serious underlying health conditions. According to the CDC, as of July, about three-quarters of breakthrough infections causing hospitalisations or death were in those aged 65 and over. One study found 44 per cent were immunocompromised, similar to trends seen in Israel, and in another trial 46 per cent of organ transplant patients did not mount an antibody response after their two doses of vaccine. That’s why some countries such as France, the US and Israel are already recommending a third booster shot of COVID vaccine for immuno-compromised patients.
But, in rare cases, people who are otherwise healthy might still die or get severe disease from a breakthrough infection. “The more cases we see in vaccinated people, the more chances of that, the bigger the spectrum of outcomes, just like with unvaccinated people,” Griffin says. “But in vaccinated populations, the risks are still much, much lower, close to zero.” On such a big scale, “there will always be that one unlucky person who does everything right and gets sick”.
As for the risk of developing long covid, where symptoms of the virus drag on for many months, Griffin says that is still being understood. “But if you get a breakthrough, [the risk] seems to be reduced by at least half as well.”
And there’s another silver lining for those who fall sick after vaccination – while vaccine immunity, as with almost all immunity, wanes over time, those who have had breakthrough infections after two doses seem to wind up with higher protection again. Four weeks after an outbreak in an aged care home in the US, for example, fully vaccinated residents who had fallen ill had much higher antibody levels than those vaccinated who didn’t get sick.
“Of course, we’re not encouraging vaccinated people to go out and get infected, but it’s probably the best combination, getting a booster from natural infection plus the vaccine,” Griffin says.
Can vaccinated people spread the virus?
Yes, but how much is still a live question. Most studies use viral load (how much virus a person seems to be shedding) as a measure of infectivity. Beyond a certain threshold, scientists expect you to be shedding enough virus to infect those around you. Numerous studies around the world, as well as the CDC’s findings from the Massachusetts Cape Cod outbreak, have found vaccinated people who get infected appear to shed just as much virus as those who are not.
“But it’s not a precise metric,” Griffin says. “Even measuring viral load from PCR [swab] test results isn’t exact.”
That’s why household transmission studies are also important, he says. They consider how many other cases someone with the virus has spawned. In April, a large study of UK households found that the risk of passing on the virus fell by about half when someone was vaccinated with the Pfizer and AstraZeneca shots. That study was conducted before the latest surge of the Delta variant, though, and its higher viral load is likely to make breakthrough infections more contagious. But the science here is still crystalising – another study from June suggests vaccinated people may be infectious for shorter durations.
What does that mean for reopening?
Many reopening plans around the world, including the concept of vaccine passports, are based on the assumption that vaccinated people are 100 per cent safe to others, which is a misunderstanding of the science, according to Professor Nikolai Petrovsky of Flinders University. In fact, as breakthrough infections are more likely to be asymptomatic and so avoid detection, Petrovsky worries about a false sense of security developing as vaccinations increase in high-risk settings such as aged care.
“We’re not going to have a true ‘freedom day’ where we can stop getting tested.”Dr Paul Griffin
Still, Griffin says that doesn’t mean the vaccinated shouldn’t have more freedoms. After all, vaccine passports for diseases such as yellow fever have been around for decades. “We need to get the balance right,” he says, “to coexist with the virus in a way that’s sensible and practical, with the minimum amount of imposition on our lives, that gives us the most bang for our buck but still keeps transmission to a level that’s manageable.”
First, he says, that means targeting the highest vaccination rate we can, say, 80 per cent or higher, because we know breakthroughs will happen. But, unlike in Israel, it means keeping some basic public health measures such as hand hygiene, testing, checking in and tracing, as we reopen, a strategy outlined in the Doherty Institute modelling underpinning the national path out of the pandemic.
“And, while this is not as popular, I think we should get used to wearing masks when we can’t socially distance, say, when we’re getting back on planes, or maybe a longer bus ride. People do need to understand that we’re not going to have a true ‘freedom day’ where we can throw our masks in the bin and stop getting tested. Not for the foreseeable future.”
Petrovsky says part of the problem is how the new vaccines have been sold to the public. “It’s not a problem of the vaccines, it is the misperception of what they can and can’t deliver.”
The current vaccines do become less effective over time and against some variants, including Delta, but their protection against severe disease and death is still strong for now, Griffin says.
Petrovsky and other researchers are now hoping to make them even stronger. Boosters tweaked to better attack new variants of the virus are already planned for wealthy nations in the next year and improved second-generation vaccines (of the kind Petrovsky is helping develop for company Vaxine) “might even get us closer to preventing infection itself too”, Griffin says.
While all eyes are on the latest variant of interest showing signs of evading vaccines – the Mu strain out of Columbia – he says we are yet to see a true “escape variant” that smashes easily through the immunity conferred by the shots. “Every case, though, is an opportunity for the virus to mutate and evolve in our bodies. There’s a bit of talk that vaccination rates are what have put selective pressure on the virus to evolve faster [into new variants] to begin with and that’s true, strictly speaking, but the benefits of vaccination obviously outweigh that. It’s already saved so many lives and reduced the burden of disease.”
Breakthrough infections do mean that we are likely to keep seeing more of these variants, he says, but they don’t necessarily mean the dream of herd immunity is over. With such leaks comparatively low, the strategy still holds: the more people we vaccinate, the fewer cases overall, and so the fewer chances the virus has of evolving.
Still, while Griffin says people should not be unduly alarmed by breakthrough infections, he thinks countries including Australia should monitor them more closely. “I think we need a basic level of surveillance to see if the rate [of breakthroughs] changes. If we had a very sharp increase, we’d obviously be interested in sequencing [the genetics of those viral samples] to see if we are dealing with a new variant.”
“Breakthrough infection monitoring will be really useful to guide when we might need booster shots, how we roll those out best … how we get out of this thing.”
A spokesman for Australia’s Department of Health says “data on breakthrough infections is a matter for states and territories” and some are already collecting it. But he adds that the federal government’s expert advisory panel ATAGI is “closely monitoring local and international data about the frequency and severity of COVID‑19 infection in fully vaccinated individuals to inform future booster strategies”. The group is also reviewing international data on the safety and effectiveness of giving additional doses for high-risk patient populations and the population more generally. It’s expected to give further advice on boosters in the coming months.
“To address any longer-term immunity or emerging variants,” he says the government has already ordered 15 million boosters of Moderna and 51 million doses of the Novavax protein vaccine, which is awaiting approval after strong clinical trial results, and which can be used as a booster. As well as the 40 million Pfizer doses being rolled out in Australia’s first wave of vaccination, 60 million boosters have been ordered for 2022 and 25 million for 2023.
By : Sherryn Groch – THE AGE