Although severe COVID-19 is uncommon in children, they remain susceptible to multisystem inflammatory syndrome (MIS-C), long COVID, and the indirect effects of the pandemic, including social isolation and educational disruption. While mRNA vaccines have demonstrated high efficacy in children, data on the effectiveness of inactivated virus vaccines, such as CoronaVac, against the Omicron variant in this age group is limited. This study addresses this gap by evaluating the effectiveness of CoronaVac in Brazilian children aged 6-11 years, who were eligible for vaccination starting January 21, 2022. The study's importance stems from the need for robust data on vaccine effectiveness during the Omicron period to inform public health policies, particularly regarding measures like mask mandates in schools. The low vaccine uptake in Brazil (6.2% for the 1st dose and 26.6% for the second dose across all vaccines, and 35.1% and 19.8% for CoronaVac for the 1st and 2nd doses respectively) further highlights the urgency of understanding CoronaVac's effectiveness in this context.

Randomized clinical trials have shown high mRNA vaccine efficacy and immunogenicity in children and adolescents. However, there's a lack of data on the effectiveness of inactivated-virus vaccines like CoronaVac, especially against the Omicron variant (B.1.1.529) in children aged 6–11 years. Studies on other inactivated vaccines in children during Omicron outbreaks have been reported, but this study is specifically focused on CoronaVac's efficacy in this age group during the Omicron period within the Brazilian context.

This study employed a test-negative design, a case-control study within a tested population. Data were sourced from three national surveillance systems: e-SUS Notifica (for RT-PCR and antigen tests), SIVEP-Gripe (for severe acute respiratory illness), and SI-PNI (the national immunization system). The study period encompassed January 21, 2022, to April 15, 2022, during Omicron's dominance in Brazil. 197,958 tests were performed on children aged 6–11 years, yielding 89,955 cases (positive tests) and 108,463 controls (negative tests). Cases were confirmed COVID-19 infections via positive RT-PCR or antigen tests, while controls had negative results and similar symptoms. Severe COVID-19 was defined as a positive test within 14 days of hospital admission. The analysis excluded individuals older than 11, those who received vaccines other than CoronaVac, asymptomatic individuals, individuals with insufficient data, those with a short interval between doses, and those who received a third dose. Logistic regression was used to calculate odds ratios (ORs) comparing vaccinated and unvaccinated individuals. Vaccine effectiveness (VE) was calculated as (1-OR) × 100. The model adjusted for age, sex, ethnicity, time, region of residence, socioeconomic position, previous SARS-CoV-2 infection, and comorbidities. Missing ethnicity data were imputed using multiple imputation. The study adhered to the RECOG protocol and received ethical approval.

The study found that, among children aged 6–11 years, the VE against symptomatic COVID-19 was 21.2% (95% CI 18.6–23.8) 17 days after the first dose of CoronaVac and increased to 39.8% (95% CI 33.7–45.4) at ≥14 days post-second dose. Regarding hospitalization, the adjusted VE was 47.1% (95% CI 26.6–62.7) at ≥14 days post-first dose and 59.2% (95% CI 11.3–84.5) at ≥14 days post-second dose. For ICU admission, there were only two cases among children who received two doses at ≥14 days, resulting in a VE of 20.9% (95% CI 17.7–85.0). No deaths were observed among children who received two doses. Sensitivity analyses using multiple imputations for missing ethnicity data yielded similar results. Table 1 in the original paper provides a detailed breakdown of the odds ratios and vaccine effectiveness for symptomatic infection and hospital admission.

The findings indicate that two doses of CoronaVac offered limited protection against symptomatic COVID-19 infection among children during the Omicron period in Brazil. While a modest level of protection against hospitalization was observed, this protection was not substantial. These results underscore the importance of considering the limitations of inactivated vaccines in the context of highly transmissible variants like Omicron. Further research is needed to explore the reasons behind the relatively low effectiveness and to inform the development and implementation of effective vaccination strategies against future variants in this vulnerable population. The study's large sample size and use of a test-negative design strengthen its conclusions, although the limitations of observational studies must be considered.

This large-scale observational study demonstrated that two doses of CoronaVac provided only modest protection against symptomatic infection and hospitalization in Brazilian children aged 6–11 years during the Omicron wave. These findings highlight the need for ongoing surveillance and research to assess the effectiveness of vaccines against emerging variants and inform optimal vaccination strategies for children. Future research could focus on exploring the effectiveness of booster doses or different vaccine formulations in this age group.

As an observational study, this research is susceptible to various biases. The study relied on routinely collected data, which might have inherent limitations in terms of data quality and completeness. Furthermore, the relatively low vaccination coverage in the study population could influence the precision of the VE estimates. The study design was limited by its inability to explore specific factors that could have affected vaccine effectiveness, including individual-level immune responses and the precise viral lineage circulating in different regions.