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Superimmunity against COVID: how it is generated, according to Harvard experts

A growing body of scientific evidence posits that vaccination plus natural immunity from exposure to the coronavirus leads to particularly strong protection, even against many variants of the virus. The so-called hybrid immunity, that is, the natural immunity of an infection combined with the immunity provided by the vaccine, seems to result in stronger protection than the simple infection or vaccination alone.

Thus, the vaccine against COVID-19 plus the infection can lead to months of immunity, according to Harvard scientists in new studies carried out to find out what protection this double acquired immunity confers.

Miguel Hernan, an epidemiologist at the Harvard TH Chan School of Public Health in Boston, Massachusetts, said studies show the almost universal benefit of full vaccination, even in those who have already had COVID-19. And he warned that some nations have issued statements encouraging people who have had COVID-19 to receive a single dose of vaccine: a measure that “may be justified in an environment of vaccine shortages, but is not convenient for the time to be properly protected at the immunological level”, highlighted the expert.

Not long after countries began rolling out vaccines, researchers began noticing unique properties of vaccine responses in people who had previously been infected with and recovered from COVID-19.

“We saw that the antibodies reach these astronomical levels that exceed what you get with just two doses of the vaccine,” explained Rishi Goel, an immunologist at the University of Pennsylvania in Philadelphia, who is part of a team studying superimmunity, or immunity. hybrid, as most scientists call it.

In a recent scientific study carried out in Brazil and published in The Lancet, he collected data from infected and vaccinated patients before the appearance of the Omicron variant. Julio Croda, infectious disease doctor and epidemiologist at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Croda and his colleagues analyzed Brazil’s vaccination and infection databases to prove that the claims of Brazilian President Jair Bolsonaro, who said that since he already had COVID-19, he therefore did not need to be vaccinated, were wrong.

The researchers found that between February 2020 and November 2021, people who had previously been infected with SARS-CoV-2 and then received a dose of the vaccine — made by Pfizer-BioNTech, Oxford-AstraZeneca, SinoVac or Johnson & Johnson—averted up to 45% of the COVID-19 cases the group would have been expected to contract without vaccination.

Full courses of two-dose vaccines prevented up to 65% of expected infections and more than 80% of expected cases of severe COVID-19. “The big message is this: it is necessary to have a complete vaccination schedule for COVID-19,” Croda said.

Some authorities consider previous infections when deciding who should have access to public places, such as concerts and restaurants, but others consider only vaccination status. Peter Nordström, an epidemiologist at Umeå University in Sweden, says this dichotomy led him and his colleagues to conduct another of the studies.

Using records collected by the Swedish Public Health Agency between March 2020 and October 2021, the researchers showed that Swedish residents who had been infected with SARS-CoV-2 had a 95% reduced risk of contracting COVID-19. 19 compared to people who had no immunity, and the protection increased for three months after infection and lasted until at least 20 months after infection. One dose of the vaccine reduced the risk of infection by an additional 50% or so, and a second dose stabilized the additional protection for six months after vaccination.

Although vaccination increases protection, Nordström believes that the immunity offered by infection alone is worth considering. “Maybe we should have immunity passports instead of vaccination passports. Therefore, you are considered immune, and less likely to spread the disease, if you have been fully vaccinated or have had a prior documented infection,” he said.

Epidemiologist Victoria Hall of the UK Health Security Agency in London and her colleagues conducted the third study by tracking infections in thousands of healthcare workers from March 2020 to September 2021. The researchers found that previous infections they prevented more than 80% of otherwise expected COVID-19 cases in the year after infection, but protection fell to about 70% after one year.

Study participants who received two doses of the Pfizer-BioNTech or Oxford-AstraZeneca vaccine after an infection had close to 100% protection for at least six to eight months after the second dose. “Protection declined over time after vaccination and also after infection, but remained persistently high in those with hybrid immunity,” Hall concluded of the recent research.

More research on hybrid immunity

Initial studies of people with hybrid immunity found that their serum, the portion of blood that contains antibodies, was much better able to neutralize immunoevasive strains, such as the Beta variant identified in South Africa, and other coronaviruses, compared to people who had never been vaccinated. they had faced SARS-CoV-2. It was unclear whether this was due to high levels of neutralizing antibodies alone or to other properties.

The most recent studies suggest that hybrid immunity is due, at least in part, to immune agents called memory B cells. Most of the antibodies produced after infection or vaccination come from short-lived cells called plasmablasts, and antibody levels decline when these cells inevitably die. Once the plasmablasts are gone, the main source of antibodies becomes the much rarer memory B cells that are triggered by infection or vaccination.

A separate study found that, compared to mRNA vaccination, infection leads to a pool of antibodies that recognize variants more uniformly by targeting diverse regions of the spike. The researchers also found that people with hybrid immunity produced consistently higher levels of antibodies, compared to vaccinated people who were never infected, for up to seven months. Antibody levels were also more stable in people with hybrid immunity, report the team led by immunologist Duane Wesemann at Harvard Medical School in Boston, Massachusetts.

Many studies of hybrid immunity have not followed previously uninfected vaccine recipients for as long as those who recovered from COVID-19, and it is possible that their B cells produce antibodies that gain potency and amplitude over time , additional doses of vaccine, or both. It can take months for a stable pool of memory B cells to establish and mature.

“It’s not surprising that infected and vaccinated people are getting a good response,” said Ali Ellebedy, a B-cell immunologist at Washington University in St. Louis, Missouri. “We are comparing someone who started the race three or four months ago with someone who started the race now.”

There is some evidence that people who received both jabs without being previously infected seem to be catching up. Ellebedy’s team collected lymph node samples from mRNA-vaccinated individuals and found signs that some of their vaccination-triggered memory B cells were acquiring mutations, up to 12 weeks after the second dose, that enabled them to recognize various coronaviruses. including some that cause common colds.

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