Estimated BNT162b2 Vaccine Effectiveness Against Infection With Delta and Omicron Variants Among US Children 5 to 11 Years of Age.

Importance: Data describing the vaccine effectiveness (VE) and durability of BNT162b2 among children 5 to 11 years of age are needed. Objective: To estimate BNT162b2 VE against SARS-CoV-2 infection among children aged 5 to 11 years during Delta and Omicron variant-predominant periods and to further assess VE according to prior SARS-CoV-2 infection status and by sublineage during the Omicron variant-predominant period. Design, Setting, and Participants: This test-negative case-control study was conducted from November 2 to December 9, 2021 (Delta variant), and from January 16 to September 30, 2022 (Omicron variant), among 160 002 children tested at a large national US retail pharmacy chain, for SARS-CoV-2 via polymerase chain reaction (PCR); 62 719 children were tested during the Delta period, and 97 283 were tested during the Omicron period. Exposure: Vaccination with BNT162b2 before SARS-CoV-2 testing vs no vaccination. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infection confirmed by PCR (regardless of the presence of symptoms), and the secondary outcome was confirmed symptomatic infection. Adjusted estimated VE was calculated from multilevel logistic regression models. Results: A total of 39 117 children tested positive and 131 686 tested negative for SARS-CoV-2 (total, 170 803; 84 487 [49%] were boys; mean [SD] age was 9 [2] years; 74 236 [43%] were White non-Hispanic or non-Latino; and 37 318 [22%] were Hispanic or Latino). Final VE analyses included 160 002 children without SARS-CoV-2 infection less than 90 days prior. The VE of 2 doses of BNT162b2 against Delta was 85% (95% CI, 80%-89%; median follow-up, 1 month) compared with the Omicron period (20% [95% CI, 17%-23%]; median follow-up, 4 months). The adjusted VE of 2 doses against Omicron at less than 3 months was 39% (95% CI, 36%-42%), and at 3 months or more, it was -1% (95% CI, -6% to 3%). Protection against Omicron was higher among children with vs without infection 90 days or more prior but decreased in all children approximately 3 months after the second dose (58% [95% CI, 49%-66%] with infection vs 37% [95% CI, 34%-41%] without infection at <3 months; 27% [95% CI, 17%-35%] with infection vs -7% [95% CI, -12% to -1%] at ≥3 months without infection). The VE of 2 doses of BNT162b2 at less than 3 months by Omicron sublineage was 40% (95% CI, 36%-43%) for BA.1, 32% (95% CI, 21%-41%) for BA.2/BA.2.12.1, and 50% (95% CI, 37%-60%) for BA.4/BA.5. After 3 months or more, VE was nonsignificant for BA.2/BA.2.12.1 and BA.4/BA.5. The VE of a booster dose was 55% (95% CI, 50%-60%) against Omicron, with no evidence of waning at 3 months or more. Conclusions and Relevance: This study suggests that, among children aged 5 to 11 years, 2 doses of BNT162b2 provided modest short-term protection against Omicron infection that was higher for those with prior infection; however, VE waned after approximately 3 months in all children. A booster dose restored protection against Omicron and was maintained for at least 3 months. These findings highlight the continued importance of booster vaccination regardless of history of prior COVID-19.