6 julio, 2022

BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age

Abstract

BACKGROUND

Limited evidence is available on the real-world effectiveness of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) and specifically against infection with the omicron variant among children 5 to 11 years of age.

METHODS

Using data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Vaccine effectiveness against documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and symptomatic Covid-19 was estimated after the first and second vaccine doses. The cumulative incidence of each outcome in the two study groups through January 7, 2022, was estimated with the use of the Kaplan–Meier estimator, and vaccine effectiveness was calculated as 1 minus the risk ratio. Vaccine effectiveness was also estimated in age subgroups.

RESULTS

Among 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17% (95% confidence interval [CI], 7 to 25) at 14 to 27 days after the first dose and 51% (95% CI, 39 to 61) at 7 to 21 days after the second dose. The absolute risk difference between the study groups at days 7 to 21 after the second dose was 1905 events per 100,000 persons (95% CI, 1294 to 2440) for documented infection and 599 events per 100,000 persons (95% CI, 296 to 897) for symptomatic Covid-19. The estimated vaccine effectiveness against symptomatic Covid-19 was 18% (95% CI, −2 to 34) at 14 to 27 days after the first dose and 48% (95% CI, 29 to 63) at 7 to 21 days after the second dose. We observed a trend toward higher vaccine effectiveness in the youngest age group (5 or 6 years of age) than in the oldest age group (10 or 11 years of age).

CONCLUSIONS

Our findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age. (Funded by the European Union through the VERDI project and others.)

Throughout the coronavirus disease 2019 (Covid-19) pandemic, children 5 to 11 years of age have been susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but have generally presented with asymptomatic infection or milder symptoms than those observed in adults.^1-3 Changes in dominant viral variants have influenced the burden and severity of disease among younger children. For example, the spread of the B.1.617.2 (delta) variant increased the incidence of pediatric Covid-19–related hospitalizations in the United States.⁴

After vaccine trials involving adults and adolescents demonstrated safety and efficacy, a randomized trial of a lower-dosage formulation of the BNT162b2 messenger RNA (mRNA) vaccine (Pfizer–BioNTech) in children 5 to 11 years of age was initiated (ClinicalTrials.gov number, NCT04816643. opens in new tab). On the basis of findings from safety and immunogenicity assessments, a dose level of 10 μg was selected as the dose for the vaccine efficacy trial.⁵ The trial, conducted when the delta variant gradually became dominant, showed a vaccine efficacy of 90.7% (95% confidence interval [CI], 67.7 to 98.3) against symptomatic Covid-19 from 7 to 126 days after the second dose.⁵ In the fall of 2021, the Food and Drug Administration, the European Medicines Agency, and the Israeli Ministry of Health authorized the BNT162b2 vaccine for administration in children 5 to 11 years of age,⁶ and on November 23, 2021, Israeli health care organizations began administering the 10-μg vaccine dose to children in this age group.⁷ The spread of infection with the B.1.1.529 (omicron) variant coincided with the vaccination campaign for children 5 to 11 years of age.⁷ By the end of December 2021, the omicron variant was the dominant strain in Israel.⁸

Randomized trials of the BNT162b2 vaccine in children 5 to 11 years of age were conducted during a period when variants other than omicron were dominant, including the delta variant. Therefore, it is important to evaluate vaccine effectiveness against the currently dominant omicron variant. Initial assessments of the effectiveness of the BNT162b2 vaccine against omicron among adults, adolescents, and children have shown that the protection conferred by the vaccine was substantially lower against infection and moderately lower (with greater variability) against hospitalization than the protection the vaccine conferred against previous variants.^9-17 In the current study, we aimed to estimate the short-term vaccine effectiveness of BNT162b2 against documented infection with SARS-CoV-2 and symptomatic Covid-19 among children 5 to 11 years of age during a period when omicron was the prevalent variant.

Methods

DATA SOURCE

Clalit Health Services (CHS) is the largest integrated health care service provider in Israel, with more than 4.7 million active members. 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. Covid-19–related data are collected by the Israeli Ministry of Health for all members. During the study period, children were required to be tested when they had contact with an infected person or if they opted to take part in any activity that required a “green pass” — a certificate issued by the Israeli Ministry of Health that allowed a person who had been vaccinated against Covid-19, had recently been infected and recovered from Covid-19, or had tested negative for Covid-19 on a recent (within the previous 24 hours) antigen test or a recent (within the previous 72 hours) polymerase-chain-reaction (PCR) test to partake in activities such as cultural events or travel abroad.

STUDY DESIGN AND POPULATION

We conducted an observational cohort study emulating a target trial. We enrolled children 5 to 11 years of age 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 recruitment date). 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). This new policy required unvaccinated persons to be tested in an official setting supervised by the Ministry of Health, whereas vaccinated persons were permitted to conduct rapid antigen tests at home. We examined testing rates of both vaccinated and unvaccinated populations before and after the change in testing policy on January 7, 2022, to gauge the effect of this change.

We evaluated vaccine effectiveness against documented SARS-CoV-2 infection, as confirmed by a positive PCR test, and against symptomatic Covid-19, which was defined as a PCR-confirmed infection with a report of any Covid-19 symptom in the patient’s electronic health record. Details of outcome definitions are provided in Table S1. We estimated vaccine effectiveness for documented infection and symptomatic Covid-19 over two separate periods — from 14 to 27 days after the first dose and from 7 to 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 on the basis of 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 5 to 11 years of age at the time of recruitment; had at least 12 months of continuous membership in CHS before recruitment; had no previous PCR, serology, or antigen test that was positive for SARS-CoV-2; had a valid residence location and assignment to a population sector; were not homebound because of medical reasons; and had no interaction with the health care system (physician appointment, hospitalization, or laboratory testing) in the 3 days preceding the recruitment date, since such interaction would potentially be an indication of a developing case of symptomatic Covid-19. On each day of recruitment, all newly vaccinated children who met the inclusion criteria were matched one to one with eligible unvaccinated children on the basis of age, sex, population sector, residential area, number of influenza vaccines received in the past 5 years, overweight status, and number of diagnosis codes in the patient’s medical record that were considered by the physician to represent chronic conditions. Thousands of diagnosis codes are included in the variable that captured background conditions; therefore, when describing the study population, we provided estimates of grouped diagnoses and key single conditions that were defined by the Centers for Disease Control and Prevention as risk factors for severe Covid-19. Definitions of population characteristic variables are provided in Table S2. This study was approved by the institutional review board at CHS, and an exemption from the requirement for informed consent from the participants was granted.

All the authors conceived of and designed the study. A subgroup of authors collected and analyzed the data and wrote the manuscript. All the authors critically reviewed the manuscript. The first and last authors supervised the study and vouch for the accuracy and completeness of the data and that the conduct of the analyses followed the study design. No one who is not an author participated in the writing of the manuscript. The funding institutions did not dictate the design of the study, have access to the data, or influence the decision to submit the manuscript for publication.

STATISTICAL ANALYSIS

In the estimation of the per-protocol effect of vaccination, data from both members of a matched pair were censored if and when the control received a vaccination; such censoring was done in order to maintain the comparability of the two study groups with respect to the matching factors. The control for whom data were censored could be rerecruited as a vaccinated person if a new matched unvaccinated control was found. Follow-up also ended when a person had an outcome or died or the end of the study period was reached (in the latter two circumstances, the patient data were 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. Risk ratios and risk differences were calculated by dividing and subtracting the period-specific risk estimates, respectively. Vaccine effectiveness was defined as 1 minus the risk ratio, and 95% confidence intervals were estimated with the use of the nonparametric percentile bootstrap method with 500 repetitions. Estimates in each period included only matched pairs in which both members of the pair were still undergoing follow-up at the beginning of the period relevant for that analysis. We also conducted subgroup analyses according to age (5 or 6 years, 7 to 9 years, and 10 or 11 years), examining the cumulative incidence of and comparing the vaccine effectiveness against documented and symptomatic infections 7 to 21 days after the second dose. All analyses were performed with the use of R software, version 4.1.0.¹⁸

https://www.nejm.org/doi/full/10.1056/NEJMoa2205011

Créditos: Comité científico Covid