Israeli Study Finds Strong Correlation Between Breakthrough COVID-19 Cases and Antibody Levels

Breakthrough Sheba Medical Center study could help determine which population groups are at risk of serious illness

In a world first, an Israeli study has uncovered a strong correlation between breakthrough COVID-19 infections and neutralizing antibody levels in vaccinated individuals.

The study, which was published in the New England Journal of Medicine on Wednesday, was led by Professor Gili Regev-Yochay, director of the Infectious Diseases Unit at Sheba Medical Center, Israel’s largest hospital.

Regev-Yochay presented the findings at a news conference on Wednesday.

“It turns out that if your antibody levels are high, you are more protected” against infection, she told reporters. “If they are low, then you are less protected.”

In addition, those with lower levels of neutralizing antibodies were found to be more likely to infect others.

“The rate of breakthrough infections was very low,” Regev-Yochay said. “This is in the first months after the second dose. Among these [breakthrough cases] we mostly found a very mild infection and about 33% were totally asymptomatic. Another 10% had very mild or negligible illness.”

“Yet nearly 20% had persistent symptoms for over six weeks – what we call long COVID,” she added. “Some of these had a loss of taste or smell, others had severe fatigue and a few couldn’t come back to work even after six weeks. So that is something that I would say raises concern.”

The Pfizer/BioNTech vaccine has been proven to be highly effective against severe cases of COVID-19; nevertheless, there have been documented breakthrough infections among a small percentage of vaccinated individuals.

In the Sheba study, researchers performed extensive evaluations of those who were symptomatic or had known infection exposure.

Among 11,453 fully vaccinated health care workers, 1,497, or 13.1%, underwent RT-PCR testing during the period of the study. Of those tested, 39 COVID-19 breakthrough infections were detected. Researchers found that the concentration of antibody levels in breakthrough cases were much lower than in those who were not infected.

While most breakthrough cases were mild or asymptomatic, 19% had persistent “long COVID-19” symptoms that lasted longer than six weeks, including a prolonged loss of smell, persistent cough, fatigue, weakness and shortness of breath.

Of the 39 breakthrough cases, 18 (46%) were nursing staff members, 10 (26%) were administration or maintenance workers, 6 (15%) were allied health professionals and 5 (13%) were physicians. The average age of those who were infected was 42 and most, or 64%, were women.

While the study focused on the alpha variant and not on the delta variant that has swept the globe, Regev-Yochay told The Media Line that the findings could help scientists hone in on at-risk populations and determine if there is a need for people to receive a third dose of vaccine.

“In light of the fact that we know that there is a decrease in neutralizing antibody levels, there is a decrease in the effectiveness of the vaccine to some extent,” she said. “But our research did not look at that specific question.”

“With regard to a third dose, we are still missing a bit of data in order to know who the target population will be,” Regev-Yochay said. “We are currently carrying out a large group of research studies based on these findings, exactly for this reason: to know exactly which people are at risk of developing severe illness and to understand what is happening with the delta variant.”

In 37 of the cases for whom data were available, the suspected source of infection was an unvaccinated individual. In 21 cases, this was a member of the household. None of the breakthrough cases required hospitalization.

“What we saw is that the people who got infected had three times lower [levels of] neutralizing antibodies just before they were infected,” Regev-Yochay explained.

The findings come on the heels of another recent Israeli study that found that age, gender, symptoms and time elapsed since vaccination all affect antibody levels.

Jointly conducted by researchers from Tel Aviv University and the Shamir Medical Center in central Israel, the preliminary study was published on the MedRxiv health sciences website earlier this month.

It examined antibody levels in over 26,000 blood samples taken from COVID-19 convalescents, both vaccinated and unvaccinated people.

“We investigated 26,000 individuals and we followed their immune response to COVID-19 infection and to the Pfizer vaccination,” Professor Noam Shomron, head of the Computational Genomics Laboratory at the Sackler Faculty of Medicine at Tel Aviv University, said in a video statement that was shared with The Media Line.

Shomron conducted the study together with Dr. Adina Bar Chaim of the Shamir Medical Center.

“If you are a female and you’re infected with the virus – and you are symptomatic – you will have the strongest effect above the age of 50,” Shomron said. “If you are a male and you had symptoms after being infected by the virus, you will see an up-regulation of your immune system above the age of 35.”

In other words, women above the age of 50 who were symptomatic during their infection were found to have higher levels of antibodies than men of the same age. Meanwhile, younger men aged 35 and over were found to have a rise in antibodies as well.

“We believe these differences are based on hormonal differences between males and females and we are investigating this further,” he concluded.