Abstract and Introduction
The BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine has demonstrated high efficacy in preventing infection with SARS-CoV-2 (the virus that causes COVID-19) in randomized placebo-controlled Phase III trials in persons aged 12–17 years (referred to as adolescents in this report); however, data on real-word vaccine effectiveness (VE) among adolescents are limited.[1–3] As of December 2021, the Pfizer-BioNTech vaccine is approved by the Food and Drug Administration (FDA) for adolescents aged 16–17 years and under FDA emergency use authorization for those aged 12–15 years. In a prospective cohort in Arizona, 243 adolescents aged 12–17 years were tested for SARS-CoV-2 by reverse transcription–polymerase chain reaction (RT-PCR) each week, irrespective of symptoms, and upon onset of COVID-19–like illness during July 25–December 4, 2021; the SARS-CoV-2 B.1.617.2 (Delta) variant was the predominant strain during this study period. During the study, 190 adolescents contributed fully vaccinated person-time (≥14 days after receiving 2 doses of Pfizer-BioNTech vaccine), 30 contributed partially vaccinated person-time (receipt of 1 dose or receipt of 2 doses but with the second dose completed <14 days earlier), and 66 contributed unvaccinated person-time. Using the Cox proportional-hazards model, the estimated VE of full Pfizer-BioNTech vaccination for preventing SARS-CoV-2 infection was 92% (95% CI = 79%–97%), adjusted for sociodemographic characteristics, health information, frequency of social contact, mask use, location, and local virus circulation. These findings from a real-world setting indicate that 2 doses of Pfizer-BioNTech vaccine are highly effective in preventing SARS-CoV-2 infection among Arizona adolescents. CDC recommends COVID-19 vaccination for all eligible persons in the United States, including persons aged 12–17 years.*
The PROTECT† study is a prospective cohort of persons aged 4 months–17 years initiated in Arizona in July 2021. The study seeks to understand the risk for COVID-19 and how well COVID-19 vaccines protect children and adolescents from SARS-CoV-2 infection and illness. PROTECT expanded to Florida, Texas, and Utah in late September 2021, and those sites will be included in future analyses. PROTECT is an ancillary study of the HEROES-RECOVER cohorts,§ which previously reported VE of COVID-19 vaccines among working adults aged 18–85 years using similar methods. PROTECT participants in Arizona were recruited from families of adults participating in the HEROES study and the general public. Upon enrollment, participants responded to electronic surveys collecting demographic, health and vaccination history, and prior SARS-CoV-2 infection information. Participants submitted self-collected (or parent-/guardian-collected) mid-turbinate nasal swabs weekly, irrespective of COVID-19–like illness symptoms, and collected an additional swab at the onset of any COVID-19–like illness. Self-reported signs and symptoms of COVID-19–like illness (fever, chills, cough, shortness of breath, sore throat, diarrhea, muscle or body aches, change in smell or taste, or loss of appetite or poor feeding) that occurred in the preceding 7 days were self-reported on the weekly nasal swab envelopes. Specimens were shipped on cold packs and tested by RT-PCR assay for SARS-CoV-2 at Marshfield Clinic Laboratory (Marshfield, Wisconsin). Receipt of COVID-19 vaccines was documented by self-report in electronic surveys and direct upload of vaccine card images by participants' parents or guardians. The number of hours and percentage of time participants wore masks in school and in the community were also collected via self-reported electronic surveys upon enrollment and each subsequent month.
The primary outcome measure was time to RT-PCR–confirmed SARS-CoV-2 infection in vaccinated participants compared with that in unvaccinated participants. VE was calculated using the Anderson-Gill extension of the Cox proportional-hazards models, in which unvaccinated person-time included days before receiving the first dose of a COVID-19 vaccine, and fully vaccinated person-time included number of days following 14 days after receipt of the second of 2 Pfizer-BioNTech vaccine doses. For participants infected with SARS-CoV-2, the event date for this analysis was the earlier of the collection date of the first specimen to test positive or the symptom onset date. Unadjusted VE was calculated as 100% x (1 – hazard ratio for SARS-CoV-2 infection in vaccinated versus unvaccinated participants). An adjusted model used an inverse probability of treatment weighting approach with individual propensities to be vaccinated during each week based on sociodemographic characteristics (age, sex, race/ethnicity, and household size); health information (chronic conditions and daily medication use); frequency of close social contact (school and community); percentage of time wearing masks (school and community); and local virus circulation (daily percentage of all SARS-CoV-2 tests performed in the local county returning a positive result). These predicted propensities were used to calculate stabilized weights, which were incorporated into a Cox proportional-hazards model. Robust SEs were used to account for the clustering of participants within the same household and correlation by stabilized weights. All analyses were conducted using SAS software (version 9.4; SAS Institute) or R software (version 4.1.2; R Foundation for Statistical Computing). This activity was approved by University of Arizona Institutional Review Board on which CDC relied. The study was conducted consistent with applicable federal law and CDC policy.¶
Among 1,478 participants aged 4 months–17 years in the full Arizona PROTECT cohort, 280 (18.9%) were aged 12–17 years; 32 (11.4%) of these participants were excluded based on a documented RT-PCR–positive SARS-CoV-2 test result before enrollment, three were excluded because of failure to complete weekly nasal swabs, one was excluded because vaccination information was incomplete, and one was excluded because the participant had received the mRNA-1273 (Moderna) COVID-19 vaccine, leaving 243 participants (86.8% of participants aged 12–17 years) in the analytic sample.
Approximately one half (51.4%) were male, 65.8% were from Tucson, most were aged 12–15 years (74.5%), White (87.7%), non-Hispanic (74.5%), and had private insurance (85.2%) (Table 1). Participants reported attending in-person school a mean of 28.2 (SE = 1.0) hours per week. They reported wearing a mask in school 73.3% (SE = 2.4) of the time; the SE, in part, reflects the variability in mask mandates across the state. Participants who received a positive SARS-CoV-2 test result during the study reported a lower percentage of time masked in school (48.6%, SE = 10.0) compared with those who did not receive a positive test result (75.7%, SE = 2.3) (p = 0.031). Participants also reported using masks in the community a mean of 58.5% (SE = 2.6) of the time overall, with participants who received positive SARS-CoV-2 test results reporting a lower mean percentage of community masked time (29.3%; SE = 9.0) compared with those who received negative test results (61.3%; SE = 2.7) (p = 0.003).
During the study period, 66 participants contributed 4,288 unvaccinated person-days, 30 contributed 909 partially vaccinated person-days, and 190 contributed 21,693 fully vaccinated person-days (Table 2). Most (n = 171, 70.3%) vaccinated participants entered the study fully vaccinated. The median number of fully vaccinated person-days during the analysis period was 119 (IQR = 105–133 days).
Twenty-one persons (8.6%) received positive RT-PCR SARS-CoV-2 test results (Table 1). RT-PCR–confirmed infection was more prevalent among residents of areas other than Tucson or Phoenix (p = 0.003). The majority (n = 18, 85.7%) of participants with RT-PCR–confirmed infection reported COVID-19–like illness. The remaining three participants reported being asymptomatic. Two participants with RT-PCR–confirmed infections, both unvaccinated and from the same household, sought outpatient medical care for their illness.
During the 4,288 unvaccinated person-days, 16 RT-PCR–confirmed infections were identified (incidence rate = 3.73 per 1,000 person-days) (Table 2). During the 909 person-days <14 days after receipt of the second vaccine dose, when persons were considered partially vaccinated, no RT-PCR–confirmed infections were identified. Five RT-PCR–confirmed infections occurred during 21,693 fully vaccinated person-days (incidence rate = 0.23 per 1,000 person-days). Estimated unadjusted VE of full vaccination for preventing SARS-CoV-2 infection was 94% (95% CI = 83%–98%). Estimated adjusted VE of full vaccination for preventing SARS-CoV-2 infection was 92% (95% CI = 79%–97%).
Morbidity and Mortality Weekly Report. 2021;70(5152):1761-1765. © 2021 Centers for Disease Control and Prevention (CDC)