COVID-19 Vaccine Effectiveness Against the Delta Variant in Adolescents

Largest case study on the effectiveness of COVID-19 vaccines in adolescents, published by Israel’s Clalit Research Institute in The New England Journal of Medicine.

The Clalit Research Institute, in collaboration with researchers from Harvard University, analyzed one of the world’s largest integrated health record databases to investigate the effectiveness of the Pfizer/BioNTech BNT162B2 vaccine against the Delta variant of SARS-CoV-2 in adolescents . The study provides the largest peer-reviewed evaluation of the effectiveness of a COVID-19 vaccine in adolescents in a nationwide mass vaccination setting, and the first such study in which the Delta variant was dominant. The study was conducted in Israel, an early global leader in COVID-19 vaccination rates.

The results of this study validate and complement the previously reported findings of a Pfizer/BioNTech Phase III randomized clinical trial, which focused on symptomatic infections in the face of non-Delta variants, and which included 1,983 vaccinated adolescents aged 12 and 15 years, could not accurately assess the effectiveness of the vaccine. The large size of the current study allows for a more accurate assessment of the vaccine’s effectiveness over different time periods.

The study took place from June 8, 2021 to September 14, 2021. It coincided with Israel’s fourth wave of coronavirus infection and disease, with the Delta variant (B.1.617.2) being the dominant strain in the country for new infections.

Researchers reviewed data from 94,354 vaccinated adolescents ages 12 to 18. These adolescents were carefully matched with 94,354 unvaccinated adolescents based on a comprehensive set of demographic, geographic, and health-related characteristics associated with risk of infection, risk of serious illness, health status, and health-seeking behavior. Individuals were dynamically assigned to each group based on their changing vaccination status (13,423 individuals moved from the unvaccinated cohort to the vaccinated cohort during the study). Multiple sensitivity analyzes were performed to ensure that the estimated vaccine effectiveness was robust against potential biases.

The results show that in fully vaccinated adolescents (7 to 21 days after the second dose), the risk of symptomatic COVID-19 decreased by 93% compared to unvaccinated, while the risk of documented infection was reduced by 90%. In the period immediately prior to the second dose (day 14-20 after the first dose), vaccine efficacy was lower, but still significant – the risk of symptomatic COVID-19 decreased by 57% in vaccinated individuals and the risk of documented infection by 59%. There were insufficient data to estimate the reduction in the incidence of major illness, hospitalization and mortality, as these outcomes are rare in adolescents.

The research was conducted by Dr. Noam Barda, Dr. Noa Dagan, Michael Leshchinsky, Dr. Eldad Kepten and Prof. Ran Balicer of the Clalit Research Institute, as well as Prof. Miguel Hernán and Prof. Marc Lipsitch of the Harvard TH Chan School of Public Health, and Prof. Ben Reis of Boston Children’s Hospital and Harvard Medical School.

“The extensive nationwide rollout of Israel’s COVID-19 adolescent vaccination campaign at the start of the delta variant wave provided the Clalit Research Institute with a unique opportunity to assess, through its rich and comprehensive digital datasets, the effectiveness of the adolescent vaccine against delta. in a real world,” said Prof. Ran Balicer, senior author of the study, director of the Clalit Research Institute and Chief Innovation Officer for Clalit. “These results convincingly demonstrate that this vaccine is highly effective one week after the second dose in adolescents against symptomatic COVID-19 and against all documented infections. This data should facilitate informed individual risk-benefit decisions and, in our view, provide a strong case for the opt-in to be vaccinated, especially in countries where the virus is currently widespread,” added Prof. Balicer, who also serves as chair of Israel’s national expert advisory team on COVID-19 response.

Prof. dr. 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 leading causes of vaccine hesitancy has been a lack of information about vaccine effectiveness. This careful epidemiological study provides reliable information on vaccine effectiveness, which we hope will be useful to those who have not yet decided on vaccination.”

Prof. dr. Miguel Hernán, director of the CAUSALab and professor at Harvard TH Chan School of Public Health, said: “This study is a perfect example of how randomized trials and observational health care databases complement each other. The adolescent-focused Pfizer/BioNTech vaccine trial provided compelling evidence of its effectiveness in preventing symptomatic infection, but estimates for serious diseases and specific age groups were too inaccurate.This analysis of Clalit’s high-quality database emulates the design of the original study, benchmarks and extends the findings. to confirm the effectiveness of the vaccine in adolescents. This combination of evidence from randomized studies and observational studies is a model for efficient medical research, something that is especially important in COVID times.”

Prof. dr. Marc Lipsitch, director of the Center for Communicable Disease Dynamics and professor at Harvard TH Chan School of Public Health, said: “In all studies of vaccine effectiveness, it is a major challenge to ensure that those we compare to the effect are similar in the other features that can predict whether they will become infected or sick. This is especially difficult in the context of a fast-growing age-targeted vaccine campaign. Clalit’s extraordinary database made it possible to design a study that addressed these challenges in a way that instills tremendous confidence in the conclusions drawn from the study.”

Reference: “Effectiveness of the BNT162b2 COVID-19 Vaccine Against the B.1.617.2 (Delta) Variant in Adolescents” by Ben Y. Reis, Ph.D.; Noam Barda, MD; Michael Leshchinsky, MS; Eldad Kepten, Ph.D.; Miguel A. Hernán, MD; Marc Lipsitch, D. Phil.; Noa Dagan, MD and Ran D. Balicer, MD, Oct. 20, 2021, New England Journal of Medicine.
DOI: 10.1056/NEJMc2114290

The research was funded in part by the recently announced Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and the Clalit Research Institute. “The strengthening of scientific collaboration between Harvard and Clalit, made possible by the Berkowitz Living Laboratory Collaboration, is already bearing fruit and gives us a taste of the value of healthcare systems instrumented for research,” said Prof. Isaac Kohane , chair of the Division of Biomedical Informatics at Harvard Medical School and co-director of the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration with Professor Balicer. “Israel offers a unique environment to study the vaccine and its effects, and this study is an excellent example of what can be achieved through such close scientific collaborations.”