Vaccine effectiveness of CoronaVac against COVID-19 among children in Brazil during the Omicron period

Randomized clinical trials have shown high efficacy and immunogenicity of mRNA COVID-19 vaccines in children and adolescents, but data on the effectiveness of the inactivated-virus vaccine CoronaVac against the Omicron variant in children aged 6–11 years are limited. Although severe COVID-19 is rare in children, SARS-CoV-2 has substantial public health impact in this group, including risks of MIS-C, long-COVID, and societal effects such as educational disruption. In Brazil, vaccination of children started on January 21, 2022, with CoronaVac used for those aged 6–11 years, but uptake was still modest by April 15, 2022. There were no recent estimates of CoronaVac effectiveness in this age group during Omicron circulation. This study aimed to estimate vaccine effectiveness of CoronaVac against symptomatic SARS-CoV-2 infection and hospitalization among Brazilian children aged 6–11 years during the Omicron-dominant period.

The paper references prior evidence of high efficacy and immunogenicity of mRNA vaccines in children and adolescents from randomized trials (e.g., BNT162b2). It highlights the lack of data on the effectiveness of inactivated vaccines like CoronaVac against Omicron in children. Observational studies from Chile assessed CoronaVac effectiveness in younger children, and studies from multiple settings evaluated mRNA vaccine effectiveness against Omicron in pediatric populations. The study situates its contribution within this gap by providing real-world effectiveness estimates for CoronaVac in 6–11-year-olds during Omicron in Brazil.

Design: Test-negative case–control study among symptomatic children aged 6–11 years in Brazil during the Omicron-dominant period (January 21, 2022 to April 15, 2022). Data sources: National surveillance for RT-PCR and antigen tests (e-SUS Notifica), severe acute respiratory illness hospitalizations (SIVEP-Gripe), and the national immunisation system (SI-PNI). Record linkage combined testing, vaccination, and clinical data. Population: Children 6–11 years with COVID-19-related symptoms tested within 28 days of symptom onset. Cases were those with a positive RT-PCR or antigen test; controls were those with a negative test. Severe outcomes: Hospitalization defined as a positive test within 14 days before to 4 days after admission; deaths within 28 days after a positive test. Exclusions: Individuals >11 years; those vaccinated with products other than CoronaVac; asymptomatic tests or inconsistent symptom-notification dates; dose-interval <14 days or first dose before Jan 21, 2022; a negative test within 14 days of a previous negative; a negative followed by a positive within 7 days; tests after a positive within 90 days; missing age, sex, city, sample collection, or first symptom date; any third-dose recipients. Exposure: Vaccination status by time since dose—unvaccinated; first dose (0–13 days, ≥14 days); second dose (0–13 days, ≥14 days). Covariates: Age, sex, ethnicity, month, region, socioeconomic position (IBGE-based), prior SARS-CoV-2 infection (3–6 months or >6 months), number of comorbidities associated with COVID-19. Statistical analysis: Logistic regression estimated odds ratios (OR) for vaccination among cases vs controls; vaccine effectiveness (VE) calculated as (1−OR)×100%, with 95% CIs. Missing ethnicity handled with multiple imputation (MICE). Analyses conducted in R (v4.1.1) with tidyverse; bias-reduction methods applied for rare events where appropriate. Ethics: Approved by the Brazilian National Commission in Research Ethics; informed consent waived due to use of de-identified secondary data.

- Study sample: 197,958 tests among children 6–11 years; 89,955 (45.3%) cases and 108,463 (54.7%) controls; 560 hospital admissions. Baseline characteristics were similar between positives and negatives. - Symptomatic infection VE: 21.2% (95% CI 18.6–23.8) after ≥14 days post–first dose; 30.8% (95% CI 23.2–36.8) at 0–13 days post–second dose; 39.8% (95% CI 33.7–45.4) at ≥14 days post–second dose. - Hospitalization VE: After one dose at ≥14 days, 47.1% (95% CI 26.6–62.7). After two doses, 82.4% (95% CI 44.2–97.1) at 0–13 days and 59.2% (95% CI 31.1–84.5) at ≥14 days. - ICU admission: Two cases among children vaccinated with two doses at ≥14 days; estimated VE 20.9% (95% CI 17.7–85.0) for this rare outcome. - Mortality: No deaths among children vaccinated with two doses were detected. - Sensitivity analyses with multiple imputation for missing ethnicity (~19.4%) produced results similar to primary analyses.

The study addresses the key question of CoronaVac performance in 6–11-year-old children during Omicron circulation in Brazil. Findings indicate that two doses confer modest protection against symptomatic infection and moderate protection against hospitalization, with limited precision for ICU outcomes due to small numbers. The relatively low VE against symptomatic infection aligns with evidence of immune escape by Omicron, while the protection against severe disease supports continued use of inactivated vaccines in this age group. These results inform public health policy by suggesting vaccination can reduce severe pediatric COVID-19 even when breakthrough infections remain common, and they support complementary measures (e.g., masking in schools) during periods of high transmission.

Two doses of CoronaVac in Brazilian children aged 6–11 years during the Omicron period provided modest protection against symptomatic COVID-19 and moderate protection against hospitalization. The study delivers real-world effectiveness estimates using nationwide linked surveillance and immunization data, helping guide pediatric vaccination strategies. Future research should assess durability of protection, the impact of booster doses, comparative effectiveness versus other vaccine platforms, and effectiveness against newly emerging variants and rare severe outcomes.

- Observational test-negative design may be subject to residual confounding and selection bias related to healthcare-seeking and testing behavior. - Short follow-up after the second dose for many participants (most tested within ~43 days), limiting assessment of waning. - Limited numbers for severe outcomes (ICU admissions and deaths), resulting in imprecise VE estimates for rare events. - Missing data for ethnicity (approximately 19.4%), addressed via multiple imputation, may still introduce uncertainty. - Results are specific to 6–11-year-old children in Brazil during Omicron dominance and may not generalize to other age groups, settings, or variants. - Exclusion of recipients of vaccines other than CoronaVac limits cross-platform comparisons.