In late May, Lucy, a 31-year-old retail manager, developed a cough and fever after a night out, and subsequently tested positive for Covid. Now fully recovered, she admits she considered not bothering with the vaccination when it was offered to her. "By that point, I thought I was probably immune anyway," she explains.
Meanwhile Ellen, 50, like her husband Mike, 52, is fully vaccinated, but was shocked to discover that they had both brought Covid home with them from their holiday. "I thought we were protected after our jabs," she says. "Yet we felt wiped out for a week. We did wonder if there was any point in getting the jabs at all?"
The answer to that question now appears to be an unequivocal yes.
There is growing scientific evidence that infection plus a double vaccination confers a kind of ‘superhuman immunity’. People like Lucy (who had the vaccine) and Ellen may now have a form of super-immunity that not only beats the protection offered by either vaccination or infection on their own, but may even offer defence against all future variants.
Researchers have discovered that after a prior Covid infection and two doses of either the Pfizer or Moderna vaccine, some people’s immune systems ramp up to produce a vast number of ‘flexible’ antibodies that appear to be able to respond well to many forms of coronaviruses, including future potential variants. The researchers call this ‘superhuman immunity’ or ‘hybrid immunity’.
The US research only looked at the Pfizer and Moderna vaccinations because they don’t have AstraZeneca. In a study published recently, Paul Bienasz, a virologist at Rockefeller University, and his colleagues found antibodies in these individuals that can strongly neutralise the six variants of concern tested, including delta and beta, as well as several other viruses related to SARS-CoV-2.
"Those people have amazing responses to the vaccine," says Theodora Hatziioannou, a virologist at Rockefeller University who studied such patients. "I think they are in the best position to fight the virus."
They were also able to defeat a virus specially engineered to contain 20 mutations that are known to prevent SARS-CoV-2 antibodies from binding to it. When tested, antibodies from people who were only vaccinated or who had only experienced prior infection were powerless against the lab-grown virus. But antibodies in people with the ‘hybrid immunity’ overcame it.
Scientists are now studying these patients to better understand Covid immunity. While experts agree that ‘natural immunity’ cannot be relied upon alone, and is no reason to delay or forgo vaccination, it may prove helpful in the roadmap out of the pandemic, and answer ongoing questions over who should receive booster jabs.
Calls for a programme of booster jabs in Britain this autumn have been driven by signs that coronavirus antibody levels are declining. But antibodies are not the only indicator of immunity, and several recent studies suggest that other immune cells are involved when the body responds to Covid-19.
A recent study at University College London looked at a cohort of 129 healthcare workers at high risk of an infection for 16 weeks. Of these, 57 never tested positive for the virus. The scientists discovered the healthy workers had mounted a ‘robust’ T-cell response to Covid.
T-cells are part of the body’s adaptive immune system – they remember past infections. The researchers concluded that T-cells that had encountered common colds can also recognise Covid. "The evidence points to protection originating from prior exposure to endemic common cold coronaviruses," said author Francois Balloux, professor of computational systems biology at UCL. However, he also suggested that they may have previously had Covid itself without knowing it: "Latent infection to low levels of SARS-CoV-2 might also have played a role."
Research by Public Health England, published last year, found one in four healthcare workers had high levels of T-cells which recognised Covid, suggesting they had some protection against the virus, but nearly half had never been infected. "About half the people with high levels of T-cells in their blood have not had Covid-19, as far as we could tell – the cells were probably there because of previous infection with coronaviruses other than SARS-CoV-2," the authors said.
Danny Altmann, a professor of immunology at Imperial College London, says: "The UCL study asked whether there is any immune signature that may be present in people who are exposed to the virus yet never seen to become PCR or antibody positive. Could there be some kind of innate immune pathway which for some people heads the virus off before it ever gets established?
"The paper shows evidence for this kind of response in some. But the problem is you can’t easily tell if you have it, and it surely wouldn’t be an alternative to getting vaccinated."
Previous studies have found that vaccination after infection stimulates an antibody response that’s more vigorous and probably more lasting than either recovery or vaccination alone. Studies indicate that natural immunity will last for around eight months. After about a year, the immune system may become more vulnerable to variants.
However, vaccination boosts the immune system’s memory of the coronavirus. In one study, researchers found that people who were both previously infected and vaccinated developed 100 times the protective antibodies against the beta variant, compared to those who only were infected.
And a recent report published by the US Centers for Disease Control and Prevention concluded that people vaccinated after catching Covid have half the risk of reinfection compared with previously infected people who haven’t been vaccinated at all. The effect is so powerful that several articles have concluded that one dose is enough to protect those who have previously had Covid and made antibodies. France, Germany and Italy are among the countries that advise just one dose for these people.
Eleanor Riley, a professor of immunology and infectious disease at the University of Edinburgh says: "It’s not unusual for infection to provide broader protection than vaccination. The vaccine contains the spike protein, which is only one of more than 20 proteins that the virus makes. Potentially, this means that previously infected people may have immune systems that recognise and mobilise against more of the whole virus, including parts that are less liable to mutations than the spike. This could protect you against future variants."
The downside of this research is that you’d have to catch the virus first, which puts you at serious risk. Plus, infection doesn’t guarantee you’ll make a good immune response afterwards. A study from the University of Pennsylvania has found that up to a third of people who have previously tested positive for Covid make no antibodies at all. This is likely to happen if they are young and have only a mild case.
Says Riley: "The immune response after vaccination is much more predictable and being vaccinated will give your body every opportunity to mount a good immune response if you are subsequently exposed to the virus." The good news is that hybrid immunity may kick in regardless of whether people are infected before or after being vaccinated – and flexible antibodies may develop even in people who are ‘just’ double-vaccinated.
In a recent study, immunologist John Wherry, at the University of Pennsylvania, Wherry and his colleagues showed that uninfected people who have had two doses of Covid vaccine also start to make more flexible antibodies that can better recognise variants. Riley says: "Antibodies improve in efficacy over time. We may have fewer antibodies, but the ones we have are better and more effective. It appears that it’s a case of ‘survival of the fittest’."
And while the news of ‘breakthrough infections’ after vaccination may initially appear dispiriting, Riley says we should worry less. "Infection is much safer after vaccination and not only might not do you any harm, it could strengthen your immune response. Vulnerable people will need a booster vaccine – but if you are vaccinated, younger and otherwise healthy, a mild dose could be even better than a booster."
"Vaccination alone," she says, "can only do so much. A little bit of infection on top can enhance your immune response."
"Based on all these findings, it seems the immune system is eventually going to have the edge over this virus," says Bieniasz. "If we’re lucky, SARS-CoV-2 will eventually fall into that category of viruses that gives us only a mild cold."