Large study on the effectiveness of the Pfizer Covid-19 vaccine in children aged 5-11 published in The New England Journal of Medicine

This study represents an international collaboration of researchers from Israel, the United States and Europe, as part of the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration between the Clalit Research Institute and Harvard University in the United States, and as part of the VERDI Project funded by the European Union Horizon Program.

Researchers studied the effects of the pediatric formulation of Pfizer-BioNTech's BNT162b2 mRNA Covid-19 vaccine over the period of November 23, 2021 through January 7, 2022, as the Omicron (B.1.1.529) variant of SARS-CoV-2 became the dominant strain in Israel.

Israel was one of the first countries to launch a campaign to vaccinate children 5-11 years of age in November 2021. This nationwide study provides early evidence on the effectiveness of the pediatric Covid-19 vaccine among 94,728 vaccinated children, 5 to 11 years of age, compared to 94,728 unvaccinated children who were rigorously matched according to an extensive set of potential confounding variables. This is the first peer-reviewed cohort study to control for differences between the two study groups across many characteristics, including demographic factors, number of chronic medical conditions and health seeking behavior.

Researchers found that during a short-term follow-up, vaccination with BNT162b2 provided moderate protection: Vaccine effectiveness in days 7-21 following the second dose was estimated to be 51% against documented SARS-CoV-2 infection and 48% against symptomatic Covid-19 illness among children 5 to 11 years of age. However, protection was not uniform across all ages in the cohort, with a trend toward greater protection observed in the youngest age subgroup (ages 5 to 6 years) compared to the oldest age subgroup (ages 10 to 11 years).

The research was conducted in Israel by Dr. Chandra J. Cohen-Stavi, Dr. Ori Magen, Dr. Noam Barda, Dr. Shlomit Yaron, Dr. Alon Peretz Laufer, Prof. Leonard Leibovici, Dr. Doron Netzer, Prof. Ran Balicer and Dr. Noa Dagan, in collaboration with Prof. Carlo Giaquinto from the University of Padova, Dr. Ali Judd from University College London, Prof. Miguel Hernán and Prof. Marc Lipsitch from the Harvard School of Public Health, and Prof. Ben Reis from Boston Children’s Hospital and Harvard Medical School.

Prof. Ran Balicer, Chief Innovation Officer for Clalit, said: “We know from our previous studies that the short-term effectiveness of this vaccine in preventing symptomatic Covid-19 was very high in adolescents against the Delta strain. Our study published today suggests that the vaccine provided a more moderate protection against symptomatic infections with the Omicron strain among children aged 5-11 years. It is difficult to determine which part of this reduced protective effect may be attributed to the different dose formulation, and which part may be attributed to the vaccine’s ability to mount an effective response against the Omicron strain.”

Prof. Marc Lipsitch, Director of the Center for Communicable Disease Dynamics and Professor at the Harvard T.H. Chan School of Public Health, said, “In all studies of vaccine effectiveness, a major challenge is to ensure that those we are comparing to identify the vaccine’s effect are similar in the other characteristics that may predict whether they get infected or ill. This is especially hard in the context of a rapidly growing, age-targeted vaccine campaign. Clalit’s extraordinary database made it possible to design a study that addressed these challenges in a way that provides great confidence in the inferences that come out of the study.”

Prof. Miguel Hernán, Director of the CAUSALab and Professor at the Harvard T.H. Chan School of Public Health, said, “This research is a perfect example of how observational healthcare databases can be used to study vaccine effectiveness. The analyses of Clalit’s high-quality database first emulated the design of the original trials in adults and now extend the causal inference to children. This combined use of randomized trials and observational data is a model for efficient medical research, something which is especially important in Covid-19 times.”

Dr. Doron Netzer, Chief Medical Officer of Clalit’s Community Health Division, said: “This study sheds light on vaccine effectiveness in children 5-11 years of age. Given the thorough methodological approach to control for potential confounders, the results reliably reflect the BNT162b2 effectiveness against documented and symptomatic Covid-19 infection during the omicron wave. Clalit will continue its evidence-based approach in order to deliver the best care to its members.”

Prof. Carlo Giaquinto from the University of Padova, and the PENTA Foundation, who is the Coordinator of the VERDI Project funded by the EU, said: "This study from the Clalit data warehouse shows how real-world data can be used to quickly provide estimation on the effectiveness of new interventions, such as the pediatric formulation of Pfizer-BioNTech's BNT162b2 Covid-19 vaccine. These results present early evidence, where evidence has been limited, on how Covid-19 vaccination is also effective in the pediatric population."

Prof. Ben Reis, Director of the Predictive Medicine Group at the Boston Children’s Hospital Computational Health Informatics Program and Harvard Medical School, said: “To date, one of the main drivers of pediatric vaccine hesitancy has been a lack of information regarding its effectiveness. This careful epidemiological study provides reliable information on vaccine effectiveness, which we hope will help individuals make informed decisions about vaccination.”