- A breakthrough infection is when a person gets sick despite being vaccinated for that illness.
- Breakthrough infections in the case of Covid-19 are expected because no vaccine guarantees complete protection against infection with the SARS-CoV-2 virus.
- Although only a small number of fully vaccinated people will end up getting infected, Covid-19 jabs dramatically reduce vaccinated people’s chances of falling severely ill with the disease.
In late July, the United States (US) reversed the mask-wearing rules for people who were fully vaccinated against Covid stipulating that they’d have to again wear masks in indoor public places.
This overturned a May decision that vaccinated people could mostly stop wearing masks in public because they were well protected against infection and were unlikely to spread the virus to others.
To reduce the risk of being infected with the highly transmissible Delta variant and possibly spreading it to others, the Centres for Disease Control (CDC) now says, vaccinated people need to wear masks in indoor public spaces, especially if they live in areas of “substantial or high transmission”.
Moreover, the CDC has instructed all teachers, staff and students to wear masks, regardless of whether they have been vaccinated or not.
So why the turnabout in rules?
Breakthrough infections among people who were fully vaccinated.
July surveillance from the CDC found 469 Covid-19 cases in the town of Barnstable county, in Massachusetts.
Of the 469 cases, almost three-quarters were in people who had been fully immunised.
Among those who were infected, 90% of cases had been caused by the Delta variant, which is now also dominant in South Africa.
Data from the Washington health department found 4 241 infections in fully vaccinated people during a six-month period ending in July. At the end of that month, the state had administered 8 179 883 vaccines.
And the CDC compiled data from 49 out of America’s 50 states: of the 163-million Americans who had been fully vaccinated by July, 6 587 people had been hospitalised or died as a result of breakthrough infections.
At a press briefing, the CDC’s director, Rochelle Walensky, explained: “The Delta variant is showing every day its willingness to outsmart us.”
What are breakthrough infections?
A breakthrough infection is when a person gets sick despite being vaccinated for that illness. In the case of Covid, that would be when someone who has been fully vaccinated gets infected with the SARS-CoV-2 virus and still develops Coid-19 (with or without symptoms).
Countries such as the US have been collecting real-life data on their vaccine roll-outs and have begun seeing SARS-CoV-2 breakthroughs as a result of infection with the Delta variant. Delta was first detected in India in October and is significantly more transmissible than any other form of the virus.
As a result, the US increased the measures that fully vaccinated people need to take to protect themselves, and those around them, against SARS-CoV-2 infection. So for now, mask-wearing in public spaces for vaccinated people is on again - at least indoors.
But does that mean Covid-19 jabs aren’t working?
As the US data on breakthrough infections show, only a small proportion of people who are fully vaccinated get infected with SARS-CoV-2, and the infections tend to be mild.
The infections are generally mild, because what Covid-19 vaccines are best at doing is to protect us from falling severely ill - or dying - if we develop Covid-19.
Data from England, for instance, shows that just one shot of the Pfizer jab (we use this vaccine in South Africa and you need two doses to be fully vaccinated) reduces your chances of hospitalisation as a result of infection with the Delta variant by 94%. Two shots increase the protection to 96%.
But the protection offered by the same vaccine against developing milder forms of Covid caused by the Delta variant is lower than the protection it offers against falling severely ill.
England data shows one jab offers 36% protection against such infection and two shots reduce your chances of infection by 88%.
Most of these infections were caused by the Alpha variant, which was first identified in England and was dominant in Israel at the time. Among the breakthroughs, two-thirds were mild Covid cases and the remaining third did not develop any symptoms. ?
Getting vaccinated against Covid therefore doesn’t necessarily mean that you’re done with the disease, because there’s still a chance that you can get infected. But what it does mean is that your chances of ending up in an intensive care unit or dying of Covid are drastically lower than someone who hasn’t been vaccinated.
But it’s important to remember: No Covid-19 jab is 100% effective.
What is vaccine efficacy?
So what does it mean if the Pfizer jab provides 96% protection against hospitalisation?
What it doesn’t mean, is that 96% of people who had been fully vaccinated with the vaccine wouldn’t end up in hospital. Rather, it means that each person who gets fully vaccinated reduces their own risk of hospitalisation as a result of infection with the Delta variant by 95%.
Some people will therefore still fall seriously as a result of Covid because the protection isn’t 100%.
But there’s also something called general vaccine efficacy of Covid-19 vaccines - and that refers to someone’s risk of developing Covid after they’ve been immunised.
Each Covid-19 vaccine has its own efficacy. So the efficacy of Pfizer’s jab which offers 88% protection against developing Covid caused by Delta will be different from the efficacy of the AstraZeneca vaccine which is 67% effective against disease caused by the Delta variant.
Real-life data (such as the data from England that tells us how well the Pfizer vaccine works against the Delta variant) is different from trial data.
Trial results only tell us how much protection a vaccine can offer in an ideal setting, because studies are conducted in tightly controlled settings, which are different from real life.
In trials, all vaccinators, for instance, receive exactly the same training, and study participants all return for a second shot of a two-dose vaccine precisely the same number of days after their first dose. But in real life, things may not always play out that way.
And when a virus has been around for a while, it adapts for survival and develops mutations which can make it more transmissible or help it to escape immunity (by making the antibodies we produce as a result of vaccines work less well) - that also affects how well a jab will work in real-life.
So although Pfizer had an original efficacy of 95% in its trial (the results were shared in November 2020, before the emergence of variants) this was lower when the vaccine was rolled out. Real-life data from the US, for example, shows that the vaccine had an effectiveness of 86% in adults (and not 95%) in April 2021.
Importantly, we don’t know if Covid-19 vaccines actually prevent you from getting infected. This is because most trials were designed to detect symptomatic cases. In other words, the results from these trials are less focused on whether people are being infected with the SARS-CoV-2 virus and rather determine if people are developing the disease - Covid-19 - which the virus causes.
Because the trials are designed to pick up people’s symptoms, like a cough or fever, they could miss asymptomatic cases, where the person themselves doesn’t know they are sick.
A January paper published in JAMA estimates 30% of people with Covid don’t develop any symptoms, yet they are still infectious. The projections show that 59% of new Covid cases were caused by people who had no symptoms of the disease.
Why do breakthrough infections happen?
1. New variants can reduce the efficacy of vaccines
Variants of concern (this is how the World Health Organisation refers to forms of the virus that could potentially cause problems) are different versions of the virus, which have undergone structural changes which alter their behaviour in a significant way.
The Delta variant (currently dominant in South Africa) and the Beta variant (previously dominant in the country) are variants of concern.
One of the characteristics a variant of concern could have is that it reduces the efficacy of medical interventions, such as vaccines.
This was seen with two vaccines that underwent trials in South Africa at the time when the Beta variant was first emerging in the country last year.
With Johnson & Johnson - another jab being used in our roll-out - the protection offered by the jab in South Africa was reduced to 64% in the local trial - compared to 72% efficacy in the US, where the Beta variant wasn’t widely circulating at the time of the trial.
The other shot for which there was local data was AstraZeneca. This trial, while smaller in scale compared to Johnson & Johnson, provided the first evidence that the Beta variant could significantly impact how well vaccines worked.
The study showed that efficacy for the jab was reduced to 10% against mild to moderate disease in cases caused by the Beta variant.
A June paper published in the New England Journal of Medicine found that while vaccines were able to provide protection against new variants of the virus, this may not be enough to stop people from getting infected with variants - particularly ones that have immune escape mutations like Beta.
Early data from the United Kingdom shows that while not as extreme in nature, the Delta variant can have a similar effect on vaccines.
People who are infected with the Delta variant are estimated to have a viral load (this is how much virus they carry in their bodies) up to 1 000 times higher than the original form of the virus, which means the Delta variant can spread considerably faster than the version of the SARS-CoV-2 virus that the Covid-19 pandemic started off with, according to a preprint from China.
Real-life data from Israel’s health ministry in July found that two doses of the Pfizer vaccine were only 40% effective against symptomatic Covid-19 cases caused by the Delta variant, although the jab was 91% effective against severe disease caused by the variant.
2. Logistical reasons
If jabs have not been stored properly, it could lead to them being less effective. For example, says Linda-Gail Bekker, one of the lead researchers of South Africa’s Sisonke study, which used J&J’s Covid-19 vaccine in an implementation study on healthcare workers, if there was a break in the cold chain while transporting the vaccine, this could degrade its quality.
Or, if there were issues with the actual administering of the jab, where it’s not being injected into people’s arms correctly, the vaccine could work less well.
In these cases, you’re likely to see a series of clustered breakthroughs because the issue would affect multiple people.
What do we know about breakthrough infections in South Africa?
Because South Africa only started with its vaccination roll-out in mid-May - five months after countries such as the US - our real-life data about breakthrough infections is still limited.
But we do have at least some data from our Sisonke study that took place before our roll-out started.
In a roughly two-month period, between 17 February and 12 April, 288 368 healthcare workers had received the J&J shot through the Sisonke study. Data from this group was shared in a paper published in the New England Journal of Medicine in June.
The Sisonke researchers defined a breakthrough infection as someone who tests positive for Covid after more than 28 days have passed since they received the Johnson & Johnson jab.
This is because studies show that immunity only fully develops 28 days after being vaccinated.
Among the trial participants, 98% were perfectly fine after being vaccinated and did not report any side-effects. Within the remaining group, the most symptoms experienced were mild but 50 of the almost 300 000 trial participants had reported events that were “serious or of special interest”.
One of the categories here - which made up just under a quarter of these reports - includes people who developed Covid-19 within 28 days after being vaccinated. There were 12 such people; they represent 0.004% of trial participants vaccinated during this time period.
Because the starting point for these vaccines is that they may not prevent infection, researchers instead looked at how ill vaccinated people became if they got infected.
In a July statement released by the South African Medical Research Council, which oversaw the study, the Council said that most breakthrough infections were mild.
Although they did not specify the number of infections that had been reported in the remaining months of the study (which ended on 16 May), they found that only 2% of cases reported were people experiencing severe disease. (The exact number of breakthrough cases reported in the Sisonke trial since 12 April has not yet been released.)
But these figures still don’t provide us with the full picture of breakthrough infections, as it’s hard to tell how well the vaccine is working without a comparator group.
The next step for the analysis is to contrast infections in the group that was vaccinated against those who did not receive the jab and see how much asymptomatic, mild, moderate and severe disease occurred in both groups, Bekker explains.
That will help better say how well the vaccine has worked and how much protection it has provided.