A Swedish study has found that people previously infected with COVID-19 exhibit an even stronger immune response to vaccination than people who had never had COVID.
What did the study find about vaccination after COVID?
The new study looked at blood samples from 514 Swedish healthcare workers who were vaccinated with either the Pfizer or AstraZeneca COVID-19 vaccines starting in January 2021. Some of the workers had already had COVID-19, while others were immunologically naïve to the virus.
The Swedish team examined markers of the healthcare workers’ immune responses against SARS-CoV-2, beginning at six weeks after the second vaccine dose and continuing up to seven months post-vaccination. The study included both antibody response, which is important for neutralising an active viral infection, and the memory T-cell response, which helps the body “remember” the virus and fight it off if the person is infected again.
Following vaccination, nearly all (99.8%) of the healthcare workers showed detectable levels of IgG antibodies against the SARS-CoV-2 spike protein, which is targeted by both the Pfizer and AstraZeneca vaccines.
However, the 164 participants who had previously recovered from a confirmed SARS-CoV-2 infection had markedly higher antibody levels than those who had never been infected, at all time points and for both vaccines.
The study also investigated response to SARS-CoV-2 by memory T-cells three months after receiving the second dose of AstraZeneca and seven months after receiving the second dose of Pfizer. Again, people who had had COVID-19 before vaccination exhibited a stronger response than those who had been COVID-naïve.
Why was the immune response to vaccination stronger following infection?
Adrian Esterman, a professor in biostatistics at the University of South Australia, says the study reinforces existing evidence about the strength of so-called hybrid immunity.
“Hybrid immunity is when you have immunity from vaccination, plus immunity from recovering from natural infection,” Esterman explains. “It’s stronger and lasts longer than either of the two separately.”
Daniel Layton, an immunologist at CSIRO, says there are a few reasons why vaccination plus infection may show a stronger immune response than vaccination alone.
“The case would be that people who were infected had already developed an immune memory,” he says. “When they’re vaccinated, they’re actually building on that immune memory to give a greater immune response.”
It’s the same principle behind receiving multiple doses of a vaccine to obtain a strong immune response.
Layton also points out that natural infection exposes the immune system to a range of different SARS-CoV-2 antigens, while COVID-19 vaccines only present the immune system with one antigen – the viral spike protein. This could influence the breadth of our immune response.
Finally, the context in which we’re exposed to a viral antigen could also play a role.
“When we get a vaccine, it does stimulate a strong immune response, but being infected might stimulate a slightly different immune response because your body sees the virus and uses different danger signals,” says Layton.
It’s also worth noting that the data for the study were collected before the rise of the Omicron variant. According to Layton, it’s hard to say if the results would have differed if Omicron had been dominant at the time of the study.
What are the implications?
Both Esterman and Layton strongly caution that the study’s results are not an argument in favour of intentionally seeking out COVID infection.
“We don’t want to encourage people to get infected to try and get themselves stronger immunity,” Esterman says.
“If you get infected, it’s a bit of lottery,” he explains. “You could be one of the people who have very mild symptoms, but you could be one of those small number of people who end up getting really ill and dying, and there’s no way for us to predict which is which.”
Infection also carries a decent risk of long-term health impacts, Esterman points out – even if the initial case is not severe.
Layton agrees that the study does not imply that the benefits of natural infection outweigh the risks.
“It certainly doesn’t tell us that natural infection is in any way a suitable way to get a good immune response,” he says.
Aside from the risk of severe or long-term disease, more infections also increase the likelihood of new variants emerging. “Then our pre-existing immunity, whether it’s natural or vaccine-derived, may be less effective,” he says.
While the participants in the Swedish study were mostly healthy, working-age adults, more infections also bring a higher risk of spreading the virus to elderly or vulnerable people in the community.
Layton says that people who have recovered from infection should still get vaccinated against SARS-CoV-2 to obtain robust immunity.
Esterman agrees: “We now have a high level of people [in Australia] who have been infected and recovered – we need to explain to them why it’s so important that they now get vaccinated afterwards.”
The authors of the new study suggested that their findings could be helpful in informing future strategies for COVID-19 vaccination programs, although Esterman and Layton emphasise that such decisions aren’t made on the basis of individual studies.
“The advice that will come from ATAGI will have taken into account this plus much larger datasets,” Layton says.