Effectiveness of COVID-19 vaccines among children 611 years against hospitalization during Omicron predominance … – Nature.com
This is the first report of real-world effectiveness of BNT162b2 against COVID-19 hospitalization in children ages 611 during a period of almost one year predominated by the BA.4/BA.5 and X.B.B sub-lineages in a low-to-middle income country (LMIC). Completion of a primary series of the BNT162b2 vaccine was estimated to be 38% effective against COVID-19-related hospitalizations in children. This protection persisted over the study period of almost one year, with moderate, non-diminishing effectiveness over time. Our findings also suggest that a recent infection within 6 months does not significantlymodify the impact of vaccination on the risk of hospitalization.
Based on our findings, the incidence of COVID-19 hospitalization among children during the Omicron period is observed to be inversely related with the number of vaccine doses received. The incidence rate (IR) among fully vaccinated individuals was 1.5 times lower than that of the unvaccinated group (9.6 vs. 6 per 10,000,000 person-days). Previous studies evaluating the effectiveness of the BNT162b2 vaccine (VE) in the pediatric population against hospitalization predominantly during the BA.1/BA.2 Omicron waves have reported varying results. In the U.S., Price et al.8 found a VE of 68% against COVID-19-related hospitalizations, while Shi et al.14 estimated the VE to be around 50%. Similarly, in Italy, Sacco et al. reported a 41% VE against severe COVID-1913. In Singapore, Tan et al. estimated a very high VE of 85% over a two-month observation period11. Nonetheless, a casecontrol study in Hong Kong estimated the VE of the BNT162b2 vaccine against COVID-19 hospitalizations in children from January to August 2022 to be 44.7% (95% CI 3.4, 68.4%)15. While there is a paucity of research focusing on pediatric primary vaccination for the BA.4/BA.5 and X.B.B sub-lineages, our findings and study duration align with those from the latter study in Hong Kong. The comparatively lower VE observed in this study likely stems from heightened community immunity, attributable to multiple infection waves and potential undetected cases, alongside reduced severity in pediatric populations due to physiological differences, such as lower ACE2 expression in nasal pathways16,17,18. Vaccine effectiveness (VE) against hospitalization with the BNT162b2 vaccine without a booster more than 150 days after the last dose in older age groups, was lower than 50%. Similarly, higher VE was observed after administering a booster dose, as indicated by COVID-19 VE pooled data from the I-MOVE-COVID-19 VE network in Europe19. Determining superior immunity in children compared to older age groups, or vice versa, poses challenges due to variations in the primary dose timeframe. Additionally, individual risk of exposure to SARS-CoV2 may differ, contributing furhterto this complexity.
Additionally, upon stratification of time intervals, we observed that vaccine effectiveness did not exhibit a distinct decline over time. Our study provides a unique perspective, underscoring the consistent and moderate protection offered by the BNT162b2 vaccine against severe disease, with an effectiveness of around 40% over a year. Our findings are consistent with findings from Hong Kong but with a greater degree of precision, further suggesting moderate non-diminishing effectiveness against COVID-19-related hospitalization in the BA.4/BA.5 and X.B.B Omicron period15.
The comparative protection provided by immunity from prior SARS-CoV-2 infection, vaccination and a hybrid of infection and vaccination has been extensively studied in the general population20,21. In children, a two-dose BNT162b2 vaccination regimen plus a prior infection (hybrid immunity) has demonstrated protection rates of 74% against Omicron BA.4/BA.5 and 62% against X.B.B. reinfections22. In adults, prior infection also provides protection against severe COVID-19 disease. However, no prior studies have explored the impact of hybrid immunity on the risk of COVID-19 hospitalization in children. Our study suggests two findings: a recent infection within 6 months appears to provide some level of protection against hospitalization, aligning with findings from other studies23. However, this effect is not statistically significant, possibly due to the small sample with prior infection of approximately 4%, indicating potential under-ascertainment during the Omicron waves or limitations in capturing infections only within the last 6 months. Interestingly, this factor also contributes to our observation that the effects of vaccination on the risk of hospitalization do not appear to be modified by a childs 6-month history of infection. While there is a possibility that the severity of COVID-19 infection following vaccination remains unchanged in those with a history of previous COVID-19 infection, this notion contradicts other research findings which suggests that hybrid immunity may confer protection against severe COVID-19, particularly in adults from high-income countries13. This limitation could have contributed to the lack of statistical significance, necessitating a cautious interpretation of our results. It is worth noting that measuring hospitalization as an outcome in children is different from assessing infection. It is important to consider that various factors can affect hospitalization rates, which may vary by location. Additionally, factors such as hospitalization criteria, bed capacity, and resource limitations must be considered, especially in low- and middle-income countries (LMICs).
Recent studies have indicated that booster doses increased VE to 58.9% in preventing hospitalizations during the BA.4/BA.5 Omicron period15. In Malaysia, the Ministry of Healths PICKids program provides the primary series to all children. It delivers booster doses after 6 to 12 months, prioritizing high-risk groups, including children with significant co-morbidities and those with immunocompromising conditions. In adolescents and older adults, vaccination rates are comparatively high; however, within the pediatric demographic, uptake is less robust, evidenced by approximately 43% receiving primary immunization series and only 0.2% having received booster doses. This disparity could be attributed to a shift in the balance of perceived risks and benefits, including concerns regarding vaccine safety. The approach has shifted from the Delta variant period's more forceful policy of mandatory vaccinations for access to public spaces and events, to the current strategy that relies on appealing to parental responsibility within the PICKids program. This change may reflect growing vaccine hesitancy24,25.However, local safety data is reassuring, with 525 reported adverse events following immunization (AEFI) among the targeted age group, equating to 158 reports per million doses, where 94% were non-serious. Of these, 34 reports were of serious AEFIs, including asthma exacerbation and Bells palsy, among children aged 5 to 11 years26.
Our results pave the way for subsequent investigative efforts. Prolonged surveillance could illuminate the enduring effectiveness of these vaccines, especially in the context of emerging viral variants. As the virus mutates and potentially presents challenges to existing vaccine formulations, there may be a demand for new vaccine compositions specifically targeting these variants. Moreover, the durability of both natural and vaccine-induced immunity may necessitate the exploration of regular booster doses, especially in populations that are more susceptible or exposed to frequent viral challenges. It is a research imperative to continue evaluating the effectiveness, safety, and optimal timing of such boosters. It is essential to delve into the broader implications of these findings on public health policies and vaccination strategies, addressing questions of effectiveness, safety, and optimal timing for booster doses in the Malaysian context.
Our approach used a large dataset with COVID-19 hospitalization as the primary measure. Our study, the largest conducted in low- and middle-income countries (LMICs) to evaluate vaccine effectiveness in children, provides greater precision than previous research. Moreover, as public health worldwide transitions to an endemic phase of COVID-19, our study examines the benefits of vaccination amidst a period of economic and social recovery and the relaxation of public health measures. We applied robust methods to address gaps in our knowledge of vaccination programs for younger children, including survival analysis, which allows participants to move between different comparison groups, thereby reducing potential biases related to unmeasured risk behaviours. Our longitudinal data also enabled us to assess how vaccine effectiveness against infection changed over time with a longer follow-up period than any previous study. While our study offers significant insights, it is not without limitations. The observational nature inherently brings potential biases. There could also be inadvertent misclassification of incidental COVID-19 cases during hospitalizations. Such situations might involve cases where patients admitted for unrelated indications with an incidentally positive test misclassified as a COVID-19 hospitalization. This misclassification could result in an underestimation of effectiveness, resembling the estimate for infection rather than accurately reflecting the effectiveness for severe outcome. Data linkage could miss matches, which could influence the reliability of estimates. Nevertheless, utilizing high-quality variables like national identification numbers is reinforced by rigorous verification and auditing at the field level, ensuring accuracy and completeness. Accounting for antecedent infections is a critical methodological consideration; however, in the context of the assessment phase and the prevalence of asymptomatic or mildly symptomatic infections, there exists a non-negligible risk of misclassification of prior infection status, a factor of heightened relevance during the Omicron phase. Furthermore, the failure to adjust for pre-existing comorbid conditions may result in the introduction of selection bias into the study results. Ultimately, the dynamics of SARS-CoV-2 epidemiology changes rapidly; hence, the applicability of these findings might be limited to the specific context captured in this study.
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