Having SARS-CoV-2 once confers much greater immunity than a vaccine, but no infection, please | Science

The natural immune protection that develops after a SARS-COV-2 infection offers considerably more protection against the Delta variant of the pandemic coronavirus than two doses of the Pfizer-BioNTech vaccine, according to a large Israeli study that some scientists would like to be accompanied by a “Don’t try this at home” label. Newly released data shows that people who have had a previous infection with SARS-COV-2 were much less likely than those vaccinated to get Delta, develop symptoms of it, or be hospitalized with COVID-19 serious.

The study demonstrates the power of the human immune system, but infectious disease experts have pointed out that this vaccine and others for COVID-19 nonetheless remain highly protective against serious illness and death. And they warn that intentional infection in unvaccinated people would be extremely risky. “What we don’t want people to say is, ‘Okay, I should go out and get infected, I should throw an infection party. Says Michel Nussenzweig, an immunologist at Rockefeller University who studies the immune response to SARS-COV -2 and was not involved in the study. “Because someone might die.”

The researchers also found that people who had previously had SARS-CoV-2 and who subsequently received a dose of the messenger RNA (mRNA) vaccine from Pfizer-BioNTech were more protected against reinfection than those who had previously had the virus. virus and were still not vaccinated.

The study, conducted in one of the most vaccinated countries against COVID-19 in the world, examined the medical records of tens of thousands of Israelis, listing their infections, symptoms and hospitalizations between June 1 and August 14 , when the Delta variant predominated in Israel. . It is the largest real-world observational study to date to compare natural and vaccine-induced immunity to SARS-COV2, according to its leaders.

The research is impressing Nussenzweig and other scientists who have reviewed a preprint of the results, posted yesterday on medRxiv. “This is a classic example of how natural immunity is really better than vaccination,” says Charlotte Thalin, physician and immunology researcher at Danderyd Hospital and the Karolinska Institute, which studies immune responses to the disease. SARS-COV-2. “To my knowledge, this is the first time [this] has really been shown in the context of COVID-19. “

Yet Thalin and other researchers point out that a deliberate infection in unvaccinated people would put them at significant risk of serious illness and death, or the persistent and significant symptoms of what has been dubbed Long Covid. The study shows the benefits of natural immunity but “does not take into account what this virus does to the body to get there,” said Marion Pepper, an immunologist at the University of Washington, Seattle. COVID-19 has already killed more than 4 million people worldwide and there are fears that Delta and other variants of SARS-CoV-2 are more deadly than the original virus.

The new analysis is based on the database of the Maccabi health system, which has an estimated 2.5 million Israelis. The study, led by Tal Patalon and Sivan Gazit at Kahn-Sagol-Maccabi (KSM), the research and innovation arm of the system, found in two analyzes that people who were vaccinated in January and February were, in June, July, and the first half of August, 6 to 13 times more likely to be infected than unvaccinated people who were previously infected with the coronavirus. In one analysis, comparing more than 32,000 people in the health care system, the risk of developing symptomatic COVID-19 was 27 times higher in vaccinees, and the risk of hospitalization 8 times higher.

“The differences are huge,” says Thalin, although she warns that the numbers of infections and other events analyzed for the comparisons were “small.” For example, the higher hospitalization rate in the analysis of 32,000 people was based on only 8 hospitalizations in a vaccinated group and 1 in a previously infected group. And the 13-fold risk of infection in the same analysis was based on just 238 infections in the vaccinated population, less than 1.5% of over 16,000 people, compared with 19 re-infections among a similar number of people who had previously had SARS-CoV. -2.

No one in the study who contracted a new SARS-COV-2 infection died, which precluded a comparison of death rates, but is a clear sign that vaccines still offer a formidable shield against serious illness. , although they are not as good as natural immunity. In addition, natural immunity is far from perfect. Although re-infections with SARS-CoV-2 are rare and often asymptomatic or mild, they can be serious.

In another analysis, the researchers compared more than 14,000 people who had a confirmed SARS-CoV-2 infection and were still not vaccinated with an equal number of previously infected people who subsequently received a dose of Pfizer-BioNTech vaccine. (In Israel, it is recommended that people who have already been infected receive a single dose.) The team found that the unvaccinated group was twice as likely to be re-infected as the individually vaccinated group.

“We continue to underestimate the importance of natural immunity against infections… especially when [infection] is recent, ”explains Eric Topol, physician-researcher at Scripps Research. “And when you bolster that with a dose of vaccine, you take it to levels that you can’t achieve with any vaccine in the world right now.”

Nusseneweig says the results in previously infected and vaccinated people confirm the lab results of a series of papers in Nature and Immunity by his group, his Rockefeller University colleague Paul BIeniasz and others – and a pre-publication published this month by Bieniasz and his team. They show, says Nussenzweig, that the immune systems of people who develop natural immunity to SARS-CoV-2 and then get vaccinated produce unusually large and powerful antibodies against the coronavirus. The preprint, for example, reported that people who had been previously infected and then vaccinated with an mRNA vaccine had antibodies in their blood that neutralized the infectivity of another virus, harmless to humans, which was designed to express a version of the coronavirus spike protein that contains 20 mutations regarding. The sera of vaccinated and naturally infected people could not do this.

When it comes to studying Israeli medical records, Topol and others point out several limitations, such as the inherent weakness of a retrospective analysis compared to a prospective study that routinely tests all participants as it tracks new infections, symptomatic infections, hospitalizations and future deaths. on time. It will be important to see these results replicated or disproved, ”says Natalie Dean, biostatistician at Emory University.

She adds: “The biggest limitation of the study is that the tests [for SARS-CoV-2 infection] is always a voluntary thing – it is not part of the study design. This means, she says, that the comparisons could be confused if, for example, previously infected people who developed mild symptoms were less likely to get tested than those who were vaccinated, perhaps because they think they are. they are immune.

Nussenzweig’s group released data showing that people recovering from SARS-CoV-2 infection continue to develop increasing numbers and types of antibodies targeting coronaviruses for up to a year. In contrast, he says, people vaccinated twice stop seeing increases “in the potency or the width of the global memory antibody compartment” a few months after their second dose.

For many infectious diseases, naturally acquired immunity is known to be more potent than immunity induced by vaccination and often lasts a lifetime. Other coronaviruses that cause serious human illness, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) trigger robust and persistent immune responses. At the same time, several other human coronaviruses, which usually cause little more than colds, are known to regularly re-infect people.