Efficacy of BNT162b2 vaccine against Omicron in children 5-11 years old
The data source
Clalit Health Services (CHS) is the largest provider of integrated health services in Israel, with over 4.7 million active members. The CHS maintains a comprehensive health care data warehouse that combines hospital and community medical records, including laboratory and imaging data and data on medication use and health care utilization. Data related to Covid-19 is collected by the Israeli Ministry of Health for all members. During the study period, children had to be tested when they were in contact with an infected person or if they chose to participate in an activity that required a “green pass” – a certificate issued by Israel’s Ministry of Health. Health that allowed a person who had been vaccinated against Covid-19, had been recently infected and recovered from Covid-19, or had tested negative for Covid-19 on a recent (within the previous 24 hours) or recent ( within the previous 72 hours) polymerase chain reaction (PCR) test to participate in activities such as cultural events or trips abroad.
Study design and population
We conducted an observational cohort study mimicking a target trial. We recruited children aged 5-11 years who were vaccinated on or after November 23, 2021, when vaccination became available for this age group in Israel. We matched each vaccinated child with an unvaccinated control on the date of vaccination (the date of recruitment). The study period ended on January 7, 2022, when a new testing policy was implemented in Israel (Fig. S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org ). The new policy required unvaccinated people to be tested in an official setting overseen by the Ministry of Health, while vaccinated people were allowed to carry out rapid antigen tests at home. We examined testing rates of vaccinated and unvaccinated populations before and after the change in testing policy on 7 January 2022, to assess the effect of this change.
We assessed vaccine efficacy against documented SARS-CoV-2 infection, confirmed by a positive PCR test, and against symptomatic Covid-19, which was defined as infection confirmed by PCR with a ratio of any Covid-19 symptom in electronic patient computer. health book. Details of the result definitions are provided in Table S1. We estimated vaccine efficacy for documented infection and symptomatic Covid-19 over two separate time periods – 14-27 days after the first dose and 7-21 days after the second dose. To assess the changing dominance of omicron variant infections in Israel over the study period, we estimated the daily proportion of omicron cases based on a sample of positive PCR test results that had been collected and sequenced by the Israeli Ministry of Health.
Children were eligible for the study if they were between the ages of 5 and 11 at the time of recruitment; had at least 12 months of continuous CHS membership prior to recruitment; had no prior positive PCR, serology, or antigen test for SARS-CoV-2; had a valid place of residence and assignment to a population area; were not confined to their homes for medical reasons; and has not had any interaction with the healthcare system (doctor’s appointment, hospitalization or laboratory tests) in the 3 days prior to the date of recruitment, as such an interaction would potentially be an indication of a developing case of symptomatic Covid-19. On each day of recruitment, all newly vaccinated children meeting the inclusion criteria were matched 1 to 1 with eligible unvaccinated children on the basis of age, sex, sector of the population, area of residence, number of influenza vaccines received in the past 5 years, overweight status, and the number of diagnostic codes in the patient’s medical record that were considered by the physician to represent chronic conditions. Thousands of diagnostic codes are included in the variable that senses background conditions; therefore, when describing the study population, we have provided estimates of grouped diagnoses and key individual conditions that have been defined by the Centers for Disease Control and Prevention as risk factors for Covid-19 strict. The definitions of the population characteristic variables are provided in Table S2. This study was approved by the CHS Institutional Review Board and a waiver of the participant informed consent requirement was granted.
All authors designed and designed the study. A subgroup of authors collected and analyzed the data and wrote the manuscript. All authors reviewed the manuscript critically. The first and last authors supervised the study and guarantee the accuracy and completeness of the data and that the conduct of the analyzes followed the design of the study. No one who is not an author participated in the drafting of the manuscript. Funding institutions did not dictate study design, have access to data, or influence the decision to submit the manuscript for publication.
In estimating the per-protocol effect of vaccination, data from both members of a matched pair were censored if and when the control received vaccination; such censoring was performed in order to maintain the comparability of the two study groups with respect to matching factors. The control whose data was censored could be re-recruited as a vaccinated person if a new unvaccinated matched control was found. Follow-up also ended when a person had a result or died or the end of the study period was reached (in the latter two circumstances, patient data was considered to have been censored).
The Kaplan-Meier estimator was used to estimate the cumulative incidence (risk) of each outcome in the vaccinated and unvaccinated groups. Relative risks and risk differences were calculated by dividing and subtracting period-specific risk estimates, respectively. Vaccine efficacy was defined as 1 minus the relative risk, and 95% confidence intervals were estimated using the percentile nonparametric bootstrap method with 500 replicates. Estimates for each period included only matched pairs in which both members of the pair were still being tracked at the beginning of the period relevant to this analysis. We also performed subgroup analyzes by age (5 or 6 years, 7 to 9 years, and 10 or 11 years), examining cumulative incidence and comparing vaccine efficacy against documented and symptomatic infections 7 21 days after the second dose. All analyzes were performed using R software, version 184.108.40.206