What Studies From Israel Say About Delta COVID, Natural Immunity and Booster Shots

A man receives his third dose of COVID-19 vaccine in Jerusalem, August 15, 2021. Photo: Reuters/Ronen Zvulun


  • A study in Israel compared 16,000 people who had had COVID-19 but didn’t get vaccinated with an equal number of people who were fully vaccinated but weren’t infected.
  • The researchers found that natural immunity to COVID-19 was more potent than vaccine-induced immunity, with caveats.
  • No deaths were reported among vaccinated persons, meaning vaccine-induced immunity remains the only feasible way to end the COVID-19 pandemic.

New Delhi: A real-world observational study in Israel has concluded that natural immunity, gained through a previous infection of COVID-19, is likely more protective against infections of the delta variant, than a full (i.e. typically a two-dose) vaccination regime.

The results indicate that those who were previously infected by the novel coronavirus had developed better immunity and also faced reduced risk of reinfection, symptomatic disease and hospitalisation due to an infection of the delta variant – versus people who had received both doses of the Pfizer vaccine but hadn’t had COVID-19.

The study’s paper, uploaded to the preprint repository medRxiv, compared more than 16,000 people who were unvaccinated but had had COVID-19 with an equal number of people who were fully vaccinated but hadn’t had COVID-19. The cohorts were infected and fully vaccinated, respectively, during January and February of 2021. The follow-up period spanned June 1 to August 14, when the delta variant was dominant in Israel.

In this period, the researchers recorded 257 cases of COVID-19 – of which 238 were breakthrough infections, i.e. reported among the vaccinated individuals. Just 19 were reported from the group that had had COVID-19. “After adjusting for comorbidities, we found a statistically significant 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection as opposed to reinfection,” the researchers wrote in their paper.

They also said 199 of the cases were symptomatic – 191 in the vaccinated group and eight in the previously infected group. After adjusting for comorbidities, the researchers reported a 27x higher risk of symptomatic breakthrough infections relative to symptomatic reinfections.

However, the researchers also observed that natural immunity against the delta variant waned if the infections occurred between March 2020 and February 2021, when other variants were common in Israel. The researchers compared the immunity among this group to people who were vaccinated during January-February 2021, and wrote:

“Although the results could suggest waning natural immunity against the delta variant, those vaccinated are still at a 5.96-fold increased risk for breakthrough infection and at a 7.13-fold increased risk for symptomatic disease compared to those previously infected. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalisation compared to those who were previously infected.”

The study also found that individuals who were previously infected with the novel coronavirus and had received a single dose of the Pfizer vaccine appeared to have gained additional protection against the delta variant.

According to The Hindu, the study didn’t say if the level and duration of protection varied depending on disease severity, and whether an asymptomatic infection confered the same ‘level’ of protection as a symptomatic one.

“Since the correlates of protection are not yet known, it is unknown if the broad immune response from natural infection might [prove] to be superior to antibodies generated in response to spike proteins in the case of vaccines,” the newspaper said. (A correlates of protection refers to a measurable quantity that signifies the level of protection – such as, for example, the amount of certain types of antibodies in the bloodstream.)

Another caveat is that the study was observational – meaning it may not have caught all asymptomatic cases of COVID-19.

While natural immunity could offer better protection against infections of the virus, The Hindu reported that since no deaths had been reported among vaccinated persons, vaccine-induced immunity remains the only feasible way to end the COVID-19 pandemic.

Empty vials of the Pfizer-BioNTech coronavirus disease (COVID-19) vaccine are seen at The Michener Institute, in Toronto, Canada January 4, 2021. Photo: Reuters/Carlos Osorio/File Photo

Booster dose?

The scientific paper itself ends with the researchers writing that the extent of long-term protection provided by a third dose of the Pfizer vaccine – which the American pharma company recently rolled out in Israel – remains unclear.

This is where two new studies – also conducted in Israel – picked up, showing that a booster dose could in fact lower the risk of infection.

Science reported that the Israeli health ministry had found that a third dose reduced the risk of infection by more than 10x, two weeks after the dose was administered. Another study, also described in a preprint paper, estimated that a third dose “roughly halves a person’s chances of testing positive for the virus starting one week after the shot and further reduces it after the second week”.

Israel started administering the booster dose to people older than 60 years from July 31, after concerns that the delta variant was causing several breakthrough infections. According to Science, cases among older people began to slow in the weeks after the booster was rolled out. And just days ago, Israel expanded the booster programme to everyone older than 12 years and who had received a second dose at least five months ago.

David Dowdy, an epidemiologist at Johns Hopkins University, told Science that if the goal is to provide someone with a high level of short-term immunity, “there’s no question that a good way to do this is … through a booster shot”.

The Israeli health ministry’s findings also reportedly showed that a booster dose cut the risk of severe disease by 15x. However, the researchers who conducted the analysis warned that the study’s short time frame and small cohort of those with severe COVID-19 mean the result has a “large uncertainty”.

Dowdyalso said that the results of these studies don’t prove that “making boosters widely available is wise”. He said studies still need to test if a booster dose meaningfully increases longer-term immunity – over many months – and if so, what the best interval to provide them might be.

If we find out that the booster dose’s additional immunity wanes quickly, it could mean that people waiting to get vaccinated – as many are in parts of Africa and Asia – will face even further delays.

Last month, the WHO called for a temporary moratorium on booster shots by wealthier countries, in order to free up doses to be sent to countries where most people haven’t even received one dose yet.

The UN body later said that current data doesn’t indicate that COVID-19 booster shots are needed at all. WHO senior adviser Bruce Aylward, referring to booster shots being administered in high-income countries, told reporters: “There is enough vaccine around the world, but it is not going to the right places in the right order.”

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