A second booster of the Pfizer COVID-19 vaccine reduced mortality rates among elderly people in Israel by 78%, according to a new study by the country’s Clalilt Health Services, Sapir College and Ben-Gurion University.

This is the largest study of its kind to date, and involved more than 560,000 people aged 60.

“The main conclusion is that the second booster [fourth shot] is lifesaving,” Dr Ronen Arbel, Health Outcomes Researcher at Clalit Health Services and Sapir College, told Health Policy Watch.

The study’s findings are in the process of being peer-reviewed by Nature Medicine journal. They were uploaded by the journal’s editor to the Research Square website so medical decision makers can have access to the data in the interim, Clalit said.

With the outbreak of the Omicron wave, the question arose as to the usefulness of giving yet another booster shot to prevent serious illness and death, especially since the Omicron appeared to cause less severe disease for the majority of people.

“The results of our study unequivocally show that the second booster vaccine is significantly associated with a reduced risk of COVID mortality, including from the Omicron strain,” said Dr Doron Netzer, head of Clalit’s Community Medical Services division.

“The results show that the Health Ministry’s decision to recommend giving an additional dose to the elderly population before the issue had been researched saved many lives in the country, with nearly a five-fold reduction in mortality risk for this population.”

Second booster offered little protection from infection – but huge protection against hospitalization 

Israel approved a fourth vaccine (second booster) for the elderly and high-risk in early January, just as a study on the fourth dose was kicking off at Sheba Medical Center, the country’s largest hospital, but before any results were available. The health ministry recommended shots specifically for people who were over the age of 60 or immunocompromised, as well as residents of retirement homes, four months after their third shot. A handful of other countries followed, including Chile and Sweden.

Since then Sheba, which ran its trial on healthcare workers, reported that the fourth shot offered “little protection, if any, from infection by COVID-19 among vaccinated young and healthy individuals in comparison to those vaccinated with only a third dose.”

That data, which included 270 people who received a fourth shot of either the Pfizer or Moderna vaccines, was published earlier this month in the New England Journal of Medicine.

“We found no differences, both in terms of igG antibody levels and in terms of neutralizing antibody levels,” said Professor Gili Regev-Yochay, who led the Sheba study, referring to the impact of the fourth jab on the study group in comparison to the control.

In contrast, Clalit’s study involved 563,465 members of its health fund between the ages of 60 and 100 (median age 73) who were eligible for the second booster shot. The patients were divided into two groups based on their vaccination status, while taking into account a variety of risk factors for mortality in order to neutralize possible biases that could result from age, gender, socio-economic status or comorbidities between the groups.

The study took place between 10 January and 20 February, the height of the first Omicron wave in Israel. Mortality due to COVID-19 among participants who received the second booster was compared with participants who received one booster dose. Death due to COVID-19 was 78% lower in the second-booster group, the study showed.

“I think it is very simple,” Arbel explained. “The Sheba study was on healthcare workers, and they were looking for infection. And we saw that a second booster shot does not stop infection. The big question is does it stop severe disease, hospitalization and death? We showed that it does.”

What about the waiting for the Omicron vaccines that Pfizer and Moderna are currently testing?

Arbel said that to his understanding those vaccines have “failed so far. Right now, we are not aware of another vaccine against COVID that is better than the original. So, what are we waiting for?”

Sheba is also taking part in the Pfizer clinical trial on the Omicron-specific vaccine shot but no official data has been released yet.

Fourth shot efficacy wanes fast

Clalit’s study was released on the same day as another smaller study conducted by Israel’s Maccabi Health Services, which also found that a second booster of the Pfizer vaccine had more than 70% efficacy in preventing COVID-19 hospitalization and death.

“The relative efficacy of the fourth versus the third dose against severe disease maintains a high level (above 73%)” for at least nine weeks,” the study, which was published on the health research sharing site MedRxiv showed. Conducted via Maccabi’s KSM Research and Innovation, it has not yet been peer-reviewed.

However, the researchers also noted that serious illness was a rare occurrence since the onset of Omicron (1%) both among those who had their third and fourth doses.

Some 10,000 Maccabi health fund members over the age of 60, who were eligible for a fourth dose, were analyzed as part of the study, which was conducted between January and March 2022.

This study looked at both infection and severe disease.

The researchers found that peak efficacy against Omicron infection occurs at around three weeks after vaccination, with a 64% relative decrease in the risk of infection for those who received a fourth shot compared to those who had only three.

However, after only eight weeks, the efficacy had already started to wane and stood at 29% at the end of 10 weeks from the fourth shot – meaning the vaccine wanes even faster between doses three and four than between doses two and three.

“More and longer-term studies are needed to determine the duration of protection given by the fourth dose over time, and how re-exposure to the same vaccine affects the efficacy of the vaccine against different variants over time,” said the Maccabi team in a statement.

Image Credits: Maccabi Health Services.