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Natural immunity appears to confer longer lasting and stronger protection against SARS-CoV-2 infection, symptomatic disease and hospitalization from the Delta variant compared to Pfizer-BioNTech’s two-dose vaccine-induced immunity, according to a new Israeli preprint study.

The new data could play a key role in determining whether people who have previously had COVID need to receive both doses of Pfizer or Moderna vaccines, Science reported.

In the largest real-world observational study comparing natural immunity gained through previous SARS-CoV-2 infection to vaccine-induced immunity afforded by the Pfizer mRNA vaccine, people who recovered from COVID were much less likely than never-infected, vaccinated people to get Delta, develop symptoms or be hospitalized.

The study, published Aug. 25 on medRxiv, was conducted in one of the most highly vaccinated countries in the world using data from Maccabi Healthcare Services, which enrolls about 2.5 million Israelis, or about 26% of the population.

Researchers examined medical records of 673,676 Israelis 16 years and older — charting their infections, symptoms and hospitalizations between June 1 and Aug. 14, when the Delta variant predominated in Israel.

The study, led by Tal Patalon and Sivan Gazit, with Maccabi’s research and innovation arm, KSM, found in two analyses that people who had never been infected with SARS-CoV-2 but were vaccinated in January and February were six to 13 times more likely to experience breakthrough infection with the Delta variant compared to unvaccinated people who were previously infected with SARS-CoV-2.

Researchers noted increased risk was significant for asymptomatic disease as well.

“This analysis demonstrated that natural immunity affords longer lasting and stronger protection against infection, symptomatic disease and hospitalization due to the Delta variant,” the researchers said.

“It’s a textbook example of how natural immunity is really better than vaccination,” Charlotte Thålin, a physician and immunology researcher at Danderyd Hospital and the Karolinska Institute, told Science. “To my knowledge, it’s the first time [this] has really been shown in the context of COVID-19.”

In one analysis that assessed more than 32,000 people in the health system, the risk of developing symptomatic COVID was 27 times higher among the vaccinated and the risk of hospitalization eight times higher, Science reported.

“The differences are huge,” said Thålin, although she cautioned the numbers for infections and other events analyzed for the comparisons were small.

Scripps’s Eric Topol pointed out several limitations with the study, such as the inherent weakness of a retrospective analysis compared with a prospective study that regularly tests all participants as it tracks new infections, symptomatic infections, hospitalizations and deaths going forward in time.

Michel Nussenzweig, an immunologist at Rockefeller University who researches the immune response to SARS-CoV-2, said the Israeli study confirms laboratory findings from a series of papers in Nature and Immunity by his group, and a study by colleague Dr. Paul Bieniasz –– whose team published a preprint earlier this month showing polyclonal antibodies against SARS-CoV-2 should be resilient to future SARS-CoV-2 variants and may confer protection against future sarbecovirus pandemics.

Nussenzweig said his group published data showing people who recover from a SARS-CoV-2 infection continue to develop increasing numbers and types of coronavirus-targeting antibodies for up to 12 months.

By contrast, Nussenzweig said, twice-vaccinated people stop seeing increases “in the potency or breadth of the overall memory antibody compartment” a few months after their second dose.

Public not getting whole truth about breakthrough cases

A closer look at the data reveals public-health communication may be overstating the vaccine’s effect on transmission and understating the scale and risk of breakthrough infections, the Intelligencer reported.

“The message that breakthrough cases are exceedingly rare and that you don’t have to worry about them if you’re vaccinated — that this is only an epidemic of the unvaccinated — that message is falling flat,” said Dr. Michael Mina, a Harvard epidemiologist.

“If this was still Alpha, sure. But with Delta, plenty of people are getting sick,” said Mina. “Plenty of transmission is going on. And my personal opinion is that the whole notion of herd immunity from two vaccine shots is flying out the window very quickly with this new variant.”

“We’re seeing a lot more spread in vaccinated people,” Topol said in an interview with Intelligencer, who estimated the vaccines’ efficacy against symptomatic transmission had dropped from 90% to 60% for Delta. Later, he suggested it might have fallen to 50%.

On Aug. 25, a large preprint study published by the Mayo clinic suggested the efficacy against infection had fallen as far as 42%.

“The breakthrough problem is much more concerning than what our public officials have transmitted,” Topol said. “We have no good tracking. But every indicator I have suggests that there’s a lot more under the radar than is being told to the public so far, which is unfortunate.”

Topol explained:

“I think the problem we have is people — whether it’s the CDC or the people that are doing the briefings — their big concern is, they just want to get vaccinations up. And they don’t want to punch any holes in the story about vaccines. But we can handle the truth. And that’s what we should be getting.”

Almost all calculations about the share of breakthrough cases have been made using year-to-date 2021 data, which include several months before mass vaccination began (when by definition vanishingly few breakthrough cases could have occurred) during which time the vast majority of the year’s total cases and deaths took place.

Two-thirds of 2021 cases and 80% of COVID deaths occurred before April 1, when only 15% of the country was fully vaccinated, which means calculating year-to-date ratios means possibly underestimating the prevalence of breakthrough cases by a factor of three and breakthrough deaths by a factor of five.

In addition, if the ratios are calculated using data sets that end before the Delta surge, that adds an additional distortion since both breakthrough cases and severe illness among the vaccinated appear to be significantly more common with this variant than with previous ones.

According to the most recent data from the Centers for Disease Control and Prevention (CDC), as of Aug. 23, 11,050 fully vaccinated people with COVID breakthrough infection had been hospitalized or died.

Unfortunately, accurate and complete data on breakthrough cases is hard to assemble. That’s because the CDC announced on May 1 it was going to stop reporting all breakthrough cases, and instead report only cases occurring in those fully vaccinated that resulted in hospitalization or death.

States currently maintain their own databases on breakthrough cases with no consensus among the states on how breakthrough cases should be counted. In Michigan, between June 15 and July 30, 19.1% of COVID cases occurred in those who were fully vaccinated.

In Utah, 8% of new cases were breakthroughs in early June, but by late July, as Delta became more prevalent, 20% of COVID cases were breakthroughs, according to NBC News.

As The Defender reported Aug. 24, about 30% of the new COVID cases in Los Angeles are breakthrough cases. The number is up from 13% in July and 5% in April.

As of Aug. 17, more than 12,500 fully vaccinated Massachusetts residents had tested positive for COVID and an additional 18 had died, NBC Boston reported.

According to CDC documents leaked to the Washington Post, there were, as of July 29, 35,000 symptomatic breakthrough cases being recorded each week — about 10% of the country’s total. Presumably many more breakthrough cases were asymptomatic, which would drive the number even higher.