Having SARS-CoV-2 once gives much greater immunity than a vaccine-but no batches of infection, thank you | Science

In January, a health professional in Jerusalem is preparing a dose of the Pfizer-BioNTech vaccine designed to prevent COVID-19.

AHMAD GHARABLI / AFP via Getty Images

By Meredith Wadman

The natural immune protection that develops after a SARS-COV-2 infection provides significantly more of a shield against the Delta variant of the pandemic coronavirus than two doses of the Pfizer-BioNTech vaccine, according to a large Israeli study by some researchers want, came up with a “Do not try this at home” label. The recently released data show that people who once had a SARS-COV-2 infection were much less likely than those vaccinated to get Delta, develop symptoms from it, or be hospitalized with severe COVID-19.

The study demonstrates the power of the human immune system, but experts in infectious diseases stressed that this vaccine and others against COVID-19 are nevertheless still extremely protective against serious illness and death. And they warn that intentional infection among unvaccinated people would be extremely risky.What we do not want people to say is, ‘Okay, I should go out and get infected, I should have an infection party.’ Says Michel Nussenzweig, an immunologist at Rockefeller University who is studying the immune response to SARS-COV -2 and was not involved in the study. “Because someone could die.”

The researchers also found that people who had previously had SARS-CoV-2 and then received a dose of the messenger RNA vaccine (mRNA) from Pfizer-BioNTech were more protected against re-infection than those who once had the virus and were still unvaccinated.

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

The research impresses Nussenzweig and other researchers who have reviewed a preprint of the results published yesterday on medRxiv. “It’s a textbook example of how natural immunity is really better than vaccination,” says Charlotte Thalin, a physician and immunology researcher at Danderyd Hospital and Karolinska Institute who studies the immune responses to SARS-COV-2. “As far as I know, this is the first time [this] has really been shown in conjunction with COVID-19. ”

Yet Thalin and other researchers stress that deliberate infection among unvaccinated people would put them at significant risk of serious illness and death or the prolonged, significant symptoms of what has been called 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 concerns that Delta and other SARS-CoV-2 variants are more deadly than the original virus.

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

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

No one in the study who got a new SARS-COV-2 infection died — which prevented a comparison of deaths, but is a clear sign that vaccines still offer a formidable shield against serious illness, even if it is not as good as natural immunity. Moreover, 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 unvaccinated with a similar number of previously infected people who subsequently received a dose of the Pfizer-BioNTech vaccine. (In Israel, it is recommended that people who have been infected in the past receive only one dose.) The team found that the unvaccinated group was twice as likely to become infected as the single vaccinated.

“We continue to underestimate the importance of natural infection immunity… especially when [infection] is recent, ”said Eric Topol, a medical scientist at Scripps Research. “And when you strengthen it with a dose of vaccine, you take it to levels you can’t possibly match with any vaccine in the world right now.”

Nusseneweig says the findings in previously infected, vaccinated humans confirm laboratory findings from a series of papers in Nature and Immunity by his group, his Rockefeller University colleague Paul BIeniasz and others – and from a pre-print sent this month by Bieniasz and his team. They show, says Nussenzweig, that the immune system in humans, which develops natural immunity to SARS-CoV-2 and is then vaccinated, produces unusually broad and potent antibodies to coronavirus. For example, the pre-expression reported that humans previously infected and subsequently vaccinated with an mRNA vaccine had antibodies in the blood that neutralized the infectivity of another virus, harmless to humans, designed to express a version of coronavirus. the spike protein containing 20 for mutations. Sera from vaccinated and naturally infected people could not do that.

Regarding the study of Israel’s medical records, Topol and others point out several limitations, such as the inherent weakness of a retrospective analysis compared to a prospective study that regularly tests all participants when it detects new infections, symptomatic infections, hospitalizations and deaths in the future. tide. “It will be important to see these findings replicate or refute,” said Natalie Dean, biostatistician at Emory University.

She adds: “The biggest limitation in the study is the testing [for SARS-CoV-2 infection] is still a voluntary thing – it’s not part of the study design. “This means,” she says, “that comparisons can be confusing if, for example. Previously infected people who developed mild symptoms were less likely to be tested than vaccinated, perhaps because they believe they are immune.

The Nussenzweig group has published data showing that people recovering from a SARS-CoV-2 infection continue to develop an increasing number and types of coronavirus-targeted antibodies for up to a year. In contrast, he says, twice-vaccinated people stop seeing increases “in the strength or breadth of the total memory antibody space” a few months after their second dose.

For many infectious diseases, naturally acquired immunity is known to be more potent than vaccine-induced immunity, and it often lasts a lifetime. Other coronaviruses that cause serious human illnesses Severe Acute Respiratory Syndrome (SARS) and Middle Eastern 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 re-infect humans on a regular basis.

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