Protection against Omicron BA.1/BA.2 severe disease 0-7 months after BNT162b2 booster.

Following evidence of waning immunity against both infection and severe disease after 2 doses of the BNT162b2 vaccine, Israel began administering a 3rd BNT162b2 dose (booster) in July 2021. Recent studies showed that the 3rd dose provides a much lower protection against infection with the Omicron variant compared to the Delta variant and that this protection wanes quickly. However, there is little evidence regarding the protection of the 3rd dose against Omicron (BA.1/BA.2) severe disease. In this study, we estimate the preservation of immunity from severe disease up to 7 months after receiving the booster dose. We calculate rates of severe SARS-CoV-2 disease between groups of individuals aged 60 and above, comparing those who received two doses at least 4 months previously to those who received the 3rd dose (stratified by the time from vaccination), and to those who received a 4th dose. The analysis shows that protection conferred by the 3rd dose against Omicron severe disease did not wane over a 7-month period. Moreover, a 4th dose further improved protection, with a severe disease rate approximately 3-fold lower than in the 3-dose cohorts.

Initial protection against SARS-CoV-2 omicron lineage infection in children and adolescents by BNT162b2 in Israel: an observational study.

BACKGROUND: The BNT162b2 (Pfizer-BioNTech) two-dose vaccine regiment for children and the BNT162b2 third dose for adolescents were approved shortly before the SARS-CoV-2 omicron (B.1.1.529) outbreak in Israel. We aimed to estimate the effects of these vaccines on the rates of confirmed infection against the omicron variant in children and adolescents. METHODS: In this observational cohort study, we extracted data for the omicron-dominated (sublineage BA.1) period. We compared rates of confirmed SARS-CoV-2 infection between children aged 5-10 years 14-35 days after receiving the second vaccine dose with an internal control group of children 3-7 days after receiving the first dose (when the vaccine is not yet effective). Similarly, we compared confirmed infection rates in adolescents aged 12-15 years 14-60 days after receiving a booster dose with an internal control group of adolescents 3-7 days after receiving the booster dose. We used Poisson regression, adjusting for age, sex, socioeconomic status, calendar week, and exposure. FINDINGS: Between Dec 26, 2021, and Jan 8, 2022, we included 1 158 289 participants. In children aged 5-10 years, the adjusted rate of confirmed infection was 2·3 times (95% CI 2·0-2·5) lower in children who received a second dose than in the internal control group. The adjusted infection rate in children who received a second dose was 102 infections per 100 000 risk-days (94-110) compared with 231 infections per 100 000 risk-days (215-248) in the corresponding internal control cohort. In adolescents aged 12-15 years, the booster dose decreased confirmed infection rates by 3·3 times (2·8-4·0) compared with in the internal control group. The adjusted infection rate of the booster cohort was 70 per 100 000 risk-days (60-81) compared with 232 per 100 000 risk-days (212-254) in the internal control cohort. INTERPRETATION: A recent two-dose vaccination regimen with BNT162b2 and a recent booster dose in adolescents substantially reduced the rate of confirmed infection compared with the internal control groups. Future studies are needed to assess the duration of this protection and protection against other outcomes such as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 and long-COVID. FUNDING: None.

Barriers and Facilitators to the Implementation of Family-Centered Technology in Complex Care: Feasibility Study.

BACKGROUND: Care coordination is challenging but crucial for children with medical complexity (CMC). Technology-based solutions are increasingly prevalent but little is known about how to successfully deploy them in the care of CMC. OBJECTIVE: The aim of this study was to assess the feasibility and acceptability of GoalKeeper (GK), an internet-based system for eliciting and monitoring family-centered goals for CMC, and to identify barriers and facilitators to implementation. METHODS: We used the Consolidated Framework for Implementation Research (CFIR) to explore the barriers and facilitators to the implementation of GK as part of a clinical trial of GK in ambulatory clinics at a children's hospital (NCT03620071). The study was conducted in 3 phases: preimplementation, implementation (trial), and postimplementation. For the trial, we recruited providers at participating clinics and English-speaking parents of CMC<12 years of age with home internet access. All participants used GK during an initial clinic visit and for 3 months after. We conducted preimplementation focus groups and postimplementation semistructured exit interviews using the CFIR interview guide. Participant exit surveys assessed GK feasibility and acceptability on a 5-point Likert scale. For each interview, 3 independent coders used content analysis and serial coding reviews based on the CFIR qualitative analytic plan and assigned quantitative ratings to each CFIR construct (-2 strong barrier to +2 strong facilitator). RESULTS: Preimplementation focus groups included 2 parents (1 male participant and 1 female participant) and 3 providers (1 in complex care, 1 in clinical informatics, and 1 in neurology). From focus groups, we developed 3 implementation strategies: education (parents: 5-minute demo; providers: 30-minute tutorial and 5-minute video on use in a clinic visit; both: instructional manual), tech support (in-person, virtual), and automated email reminders for parents. For implementation (April 1, 2019, to December 21, 2020), we enrolled 11 providers (7 female participants, 5 in complex care) and 35 parents (mean age 38.3, SD 7.8 years; n=28, 80% female; n=17, 49% Caucasian; n=16, 46% Hispanic; and n=30, 86% at least some college). One parent-provider pair did not use GK in the clinic visit, and few used GK after the visit. In 18 parent and 9 provider exit interviews, the key facilitators were shared goal setting, GK's internet accessibility and email reminders (parents), and GK's ability to set long-term goals and use at the end of visits (providers). A key barrier was GK's lack of integration into the electronic health record or patient portal. Most parents (13/19) and providers (6/9) would recommend GK to their peers. CONCLUSIONS: Family-centered technologies like GK are feasible and acceptable for the care of CMC, but sustained use depends on integration into electronic health records. TRIAL REGISTRATION: ClinicalTrials.gov NCT03620071; https://clinicaltrials.gov/ct2/show/NCT03620071.

Protection following BNT162b2 booster in adolescents substantially exceeds that of a fresh 2-dose vaccine.

Israel began administering a BNT162b2 booster dose to restore protection following the waning of the 2-dose vaccine. Biological studies have shown that a "fresh" booster dose leads to increased antibody levels compared to a fresh 2-dose vaccine, which may suggest increased effectiveness. To compare the real-world effectiveness of a fresh (up to 60 days) booster dose with that of a fresh 2-dose vaccine, we took advantage of a quasi-experimental study that compares populations that were eligible to receive the vaccine at different times due to age-dependent policies. Specifically, we compared the confirmed infection rates in adolescents aged 12-14 (215,653 individuals) who received the 2-dose vaccine and in adolescents aged 16-18 (103,454 individuals) who received the booster dose. Our analysis shows that the confirmed infection rate was lower by a factor of 3.7 (95% CI: 2.7 to 5.2) in the booster group.

Protection by a Fourth Dose of BNT162b2 against Omicron in Israel.

BACKGROUND: On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19). METHODS: Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day. RESULTS: The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks. CONCLUSIONS: Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.