Publication date: May 31, 2025

Observational evidence of COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 infection is often limited by differences in testing behavior between vaccinated and unvaccinated persons. This study aimed to estimate VE against SARS-CoV-2 infection among students using data from a school district opt-in weekly testing program. An observational, matched cohort study to emulate a target vaccine trial was conducted among students attending an urban school district in the Southeastern United States. Between 9/7/21 and 5/26/22, 9172 children, among 24,188 total students participating in the testing program, were followed from vaccination date, determined by state immunizations information systems (IIS) records, to first positive SARS-CoV-2 rapid antigen test, regardless of symptoms, conducted through the testing program. Hazard ratios and their 95 % confidence intervals were calculated using Cox proportional hazards models, and VE was calculated as (1-hazard ratio)*100. All analyses were stratified by age group (5-11 years and 12 years and older) and sensitivity analyses were conducted. Among students aged 5-11 years, VE against SARS-CoV-2 infection within 60 days of first dose of any COVID-19 vaccine was 42. 9 % (95 % CI, 7. 1 % to 78. 7 %) and waned to 20. 7 % (95 %, CI 0. 0 % to 41. 8 %) by 180 days. Over the full study period, VE against SARS-CoV-2 infection was 14. 9 % (95 % CI, -5. 0 % to 34. 7 %). Among students 12 years and older, VE against SARS-CoV-2 infection was -5. 0 % (95 % CI, -37. 0 % to 26. 5 %) over the full study period. Insufficient data was available to estimate VE within 60 days of vaccination in this age group. Among 5-11 year olds participating in a routine SARS-CoV-2 surveillance testing program, VE against SARS-CoV-2 infection was modest immediately following vaccination but waned over the school year. This analysis limits biases found in traditional VE studies related to differential testing behaviors and allows estimation of VE against infection, regardless of symptoms.

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