Effectiveness of Pfizer-BioNTech mRNA Vaccination Against COVID-19 Hospitalization Among Persons Aged 12–18 Years — United States, June–September 2021

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Pfizer-BioNTech COVID-19 vaccine is authorized for use in children and adolescents aged 12–15 years and is licensed by the Food and Drug Administration (FDA) for persons aged ≥16 (1). A randomized placebo-controlled trial demonstrated an efficacy of 100% (95% confidence interval [CI] = 75.3%–100%) in preventing outpatient COVID-19 in persons aged 12–15 years (2); however, data among adolescents on vaccine effectiveness (VE) against COVID-19 in real-world settings are limited, especially among hospitalized patients. In early September 2021, U.S. pediatric COVID-19 hospitalizations reached the highest level during the pandemic (3,4). In a test-negative, case-control study at 19 pediatric hospitals in 16 states during June 1–September 30, 2021, the effectiveness of 2 doses of Pfizer-BioNTech vaccine against COVID-19 hospitalization was assessed among children and adolescents aged 12–18 years. Among 464 hospitalized persons aged 12–18 years (179 case-patients and 285 controls), the median age was 15 years, 72% had at least one underlying condition, including obesity, and 68% attended in-person school. Effectiveness of 2 doses of Pfizer-BioNTech vaccine against COVID-19 hospitalization was 93% (95% CI = 83%–97%), during the period when B.1.617.2 (Delta) was the predominant variant. This evaluation demonstrated that 2 doses of Pfizer-BioNTech vaccine are highly effective at preventing COVID-19 hospitalization among persons aged 12–18 years and reinforces the importance of vaccination to protect U.S. youths against severe COVID-19.

This study used a test-negative design, similar to other postauthorization VE evaluations, in which vaccine performance is assessed by comparing the odds of antecedent vaccination among laboratory-confirmed case-patients hospitalized with COVID-19 and hospitalized controls without COVID-19 (5). Participants were aged 12–18 years and were admitted to 19 pediatric hospitals in the CDC-funded Overcoming COVID-19 Network during June 1–September 30, 2021 (6). Case-patients^† were hospitalized with symptomatic COVID-19–like illness and a positive SARS-CoV-2 reverse transcription–polymerase chain reaction (RT-PCR) or antigen test result; no case-patients received a diagnosis of multisystem inflammatory syndrome in children (MIS-C) during their enrolling hospitalization. Two hospitalized control groups were enrolled: 1) patients with symptoms compatible with COVID-19 with negative SARS-CoV-2 RT-PCR or antigen test results (test-negative) and 2) patients without COVID-19–associated symptoms who might or might not have received SARS-CoV-2 testing (syndrome-negative).^§ Baseline demographic characteristics, clinical information about the current illness, and SARS-CoV-2 testing history were obtained through parent or guardian interviews performed by trained study personnel and review of electronic medical records. Parents or guardians were asked about COVID-19 vaccination history, including number of doses and whether the most recent dose occurred in the last 14 days, location where vaccination occurred, vaccine manufacturer, and availability of a COVID-19 vaccination card. Study personnel searched sources, including state vaccination registries, electronic medical records, or other sources (including documentation from pediatricians) to verify reported or unknown vaccination status.

Patients were considered to have received COVID-19 vaccination based on source documentation or by plausible self-report (vaccination dates and location were provided). Because vaccination with Moderna or Janssen vaccine were not authorized for persons aged <18 years at the time of this evaluation, only receipt of Pfizer-BioNTech vaccine was assessed in this analysis. The study included fully vaccinated persons aged 12–18 years with COVID-19 vaccination status categorized as 1) unvaccinated (no receipt of any COVID-19 vaccine before illness onset^¶) or 2) fully vaccinated (receipt of 2 doses of Pfizer-BioNTech vaccine, with the second dose administered ≥14 days before illness onset). Patients who were partially vaccinated (i.e., received only 1 dose or received a second dose <14 days before illness onset) were excluded from the analysis. Descriptive statistics were used to compare characteristics of case-patients and controls. Pearson chi-square tests (categorical outcomes) or Wilcoxon rank-sum test for medians (continuous outcomes) were used to make comparisons between groups; statistical significance was defined as p<0.05. VE against COVID-19 hospitalization was calculated by comparing the odds of full COVID-19 vaccination among case-patients and controls using the equation VE = 100 × (1 – adjusted odds ratio), determined from logistic regression models. Firth penalized regression was used for models with six or fewer vaccinated case-patients. Models were adjusted for U.S. Census region, calendar month of admission, age, sex, and race/ethnicity (5). Other factors were assessed (underlying health conditions and social vulnerability index) but were not included in the final model because they did not change the odds ratio of vaccination by >5% (5). Sensitivity analyses were performed to evaluate whether VE differed by control group. VE was also stratified by age groups (12–15 and 16–18 years). Statistical analyses were conducted using SAS (version 9.4; SAS Institute). This activity was reviewed by CDC and the other participating institutions and was conducted consistent with applicable federal law and CDC policy.**

During June 1–September 30, 2021, among 572 eligible patients, 108 were excluded, including 56 who were partially vaccinated or who completed vaccination 0–13 days before illness onset, 20 who were hospitalized >14 days after illness onset, 14 case-patients who received a positive SARS-CoV-2 test result but were admitted for non–COVID-19 reasons, and 18 who were excluded for other reasons.^†† The 464 patients in the final analysis comprised 179 case-patients and 285 controls (122 [43%] test-negative and 163 [57%] syndrome-negative). Among case-patients and all controls, the median age was 15 years, 72% had at least one underlying condition, including obesity, and 68% attended in-person school (Table 1). Vaccination coverage was 3% among case-patients and 33% among controls. Case-patients more frequently resided in areas with higher social vulnerability index scores^§§ (median = 0.67) than did controls (median = 0.58) (p = 0.02). The distribution of most underlying conditions was not significantly different between case-patients and controls; however, diabetes was more prevalent among case-patients (12%) than among controls (5%) (p = 0.01), and neurologic or neuromuscular disorders were more prevalent among controls (28%) than among case-patients (12%) (p<0.01).

Among 179 COVID-19 case-patients, six (3%) were vaccinated and 173 (97%) were unvaccinated (Table 2). Overall, 77 (43%) case-patients were admitted to an intensive care unit, and 29 (16%) critically ill case-patients received life support during hospitalization, including invasive mechanical ventilation, vasoactive infusions, or extracorporeal membrane oxygenation; two of these 29 critically ill patients (7%) died. All 77 case-patients admitted to the intensive care unit, all 29 critically ill case-patients, and both deaths occurred among unvaccinated case-patients. Among 169 case-patients with available hospital discharge data, the median length of hospital stay was 5 days (interquartile range [IQR] = 2–9 days) for unvaccinated case-patients and 3 days (IQR = 2–4 days) for vaccinated case-patients.

VE against COVID-19 hospitalization was 93% (95% CI = 83%–97%) (Table 3), during the period when B.1.617.2 (Delta) was the predominant variant. Among all 99 patients classified as fully vaccinated, 96 (97%) had documentation of vaccination status. In a sensitivity analysis, VE was similar for each control group assessed independently (test-negative VE = 94%, 95% CI = 85%–98%; syndrome-negative VE = 92%, 95% CI = 80%–97%). In addition, VE was similar among 106 case-patients aged 12–15 years (VE = 91%) and 73 case-patients aged 16–18 years (VE = 94%).

Corresponding author: Samantha M. Olson, ylz8@cdc.gov.

¹CDC COVID-19 Response Team; ²Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts; ³Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; ⁴Department of Pediatrics, Baylor College of Medicine, Immunization Project, Texas Children’s Hospital, Houston, Texas; ⁵Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children’s Hospital, Little Rock, Arkansas; ⁶Department of Pediatrics, University of North Carolina at Chapel Hill Children’s Hospital, Chapel Hill, North Carolina; ⁷Division of Infectious Diseases, Children’s Hospital Los Angeles and Departments of Pediatrics and Molecular Microbiology and Immunology, University of Southern California, Los Angeles, California; ⁸Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado; ⁹Department of Pediatrics, Division of Cardiology, Louisiana State University Health Sciences Center and Children’s Hospital of New Orleans, New Orleans, Louisiana; ¹⁰Division of Critical Care Medicine, Department of Pediatrics, Akron Children’s Hospital, Akron, Ohio; ¹¹Division of Pediatric Critical Care, Department of Pediatrics, Children’s Hospital and Medical Center, Omaha, Nebraska; ¹²Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina; ¹³Division of Pediatric Infectious Diseases, Department of Pediatrics, Children’s Mercy Kansas City, Kansas City, Missouri; ¹⁴Division of Pediatric Critical Care, Department of Pediatrics, Saint Barnabas Medical Center, Livingston, New Jersey; ¹⁵Division of Critical Care Medicine, University of California, San Francisco Benioff Children’s Hospital Oakland, Oakland, California; ¹⁶Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama; ¹⁷Division of Pediatric Hospital Medicine, University of California San Diego-Rady Children’s Hospital, San Diego, California; ¹⁸Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; ¹⁹Divisions of Pediatric Infectious Diseases and Pediatric Critical Care Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota; ²⁰Division of Pediatric Infectious Diseases, Department of Pediatrics, UHealth/Holtz Children’s Hospital, Miami, Florida; ²¹Division of Critical Care Medicine, Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; ²²Departments of Anesthesia and Pediatrics, Harvard Medical School, Boston, Massachusetts.

References

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Abbreviations: IQR = interquartile range; SVI = social vulnerability index.
* Patients were enrolled from 19 pediatric hospitals in 16 states. Northeast: Boston Children’s Hospital (Massachusetts), Saint Barnabas Medical Center (New Jersey), Midwest: Akron Children’s Hospital (Ohio), Children’s Mercy Kansas City (Missouri), Children’s Hospital and Medical Center: Nebraska (Nebraska), Cincinnati Children’s Hospital Medical Center (Ohio), Mayo Clinic (Minnesota), South: Arkansas Children’s Hospital (Arkansas), University of North Carolina at Chapel Hill Children’s Hospital (North Carolina), Children’s of Alabama (Alabama), Monroe Carell Jr. Children’s Hospital at Vanderbilt (Tennessee), Medical University of South Carolina Children’s Health (South Carolina), Texas Children’s Hospital (Texas), Holtz Children’s Hospital (Florida), Children’s Hospital of New Orleans (Louisiana), West: University of California San Francisco Benioff Children’s Hospital Oakland (California), Children’s Hospital Colorado (Colorado), Children’s Hospital Los Angeles (California), University of California San Diego-Rady Children’s Hospital (California).
^† Testing for statistical significance was conducted using the Pearson chi-square test to compare categorical variables or Wilcoxon rank-sum test for medians to compare continuous data.
^§ CDC/ATSDR SVI documentation is available at https://www.atsdr.cdc.gov/placeandhealth/svi/index.html. Median SVI for case-patients and controls are based on US 2018 SVI data.
^¶ Other chronic conditions included rheumatologic/autoimmune disorder, hematologic disorder, renal or urologic dysfunction, gastrointestinal/hepatic disorder, metabolic or confirmed or suspected genetic disorder (including obesity), or atopic or allergic condition.
** COVID-19 vaccination status included the following two categories: 1) unvaccinated, defined as no receipt of any SARS-CoV-2 vaccine before illness onset and 2) fully vaccinated, defined as receipt of both doses of a 2-dose Pfizer-BioNTech vaccination ≥14 days before illness onset.
^†† Dates are based on those with documented vaccination, not plausible self-report. The date of illness onset was used for case-patients and controls with COVID-19–like illness with median value imputed if missing. For controls without COVID-19–like illness, the date of admission was used for a date of illness onset, also referred to as illness onset for this report.

Abbreviations: ICU = intensive care unit; IQR = interquartile range.
* COVID-19 vaccination status included the following two categories: 1) unvaccinated, defined as no receipt of any SARS-CoV-2 vaccine before illness onset and 2) fully vaccinated, defined as receipt of both doses of a 2-dose Pfizer-BioNTech vaccination ≥14 days before illness onset.
^† Patients were vaccinated and unvaccinated persons aged 12–18 years enrolled from 19 pediatric hospitals in 16 states. Northeast: Boston Children’s Hospital (Massachusetts), Saint Barnabas Medical Center (New Jersey), Midwest: Akron Children’s Hospital (Ohio), Children’s Mercy Kansas City (Missouri), Children’s Hospital and Medical Center: Nebraska (Nebraska), Cincinnati Children’s Hospital Medical Center (Ohio), Mayo Clinic (Minnesota), South: Arkansas Children’s Hospital (Arkansas), University of North Carolina at Chapel Hill Children’s Hospital (North Carolina), Children’s of Alabama (Alabama), Monroe Carell Jr. Children’s Hospital at Vanderbilt (Tennessee), Medical University of South Carolina Children’s Health (South Carolina), Texas Children’s Hospital (Texas), Holtz Children’s Hospital (Florida), Children’s Hospital of New Orleans (Louisiana), West: University of California San Francisco Benioff Children’s Hospital Oakland (California), Children’s Hospital Colorado (Colorado), Children’s Hospital Los Angeles (California), University of California San Diego-Rady Children’s Hospital (California).

Abbreviation: CI = confidence interval.
* Vaccine effectiveness estimates were based on odds of antecedent vaccination in case-patients vs controls adjusted for U.S. Census region, calendar month of admission, continuous age in years, sex, race/ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic other, Hispanic of any race, or unknown). Firth penalized regression was used for models with six or fewer vaccinated cases.
^† COVID-19 vaccination status included the following two categories: 1) unvaccinated, defined as no receipt of any SARS-CoV-2 vaccine before illness onset and 2) fully vaccinated, defined as receipt of both doses of a 2-dose Pfizer-BioNTech vaccination ≥14 days before illness onset.
^§ Patients were enrolled from 19 pediatric hospitals in 16 states. Northeast: Boston Children’s Hospital (Massachusetts), Saint Barnabas Medical Center (New Jersey), Midwest: Akron Children’s Hospital (Ohio), Children’s Mercy Kansas City (Missouri), Children’s Hospital and Medical Center: Nebraska (Nebraska), Cincinnati Children’s Hospital Medical Center (Ohio), Mayo Clinic (Minnesota), South: Arkansas Children’s Hospital (Arkansas), University of North Carolina at Chapel Hill Children’s Hospital (North Carolina), Children’s of Alabama (Alabama), Monroe Carell Jr. Children’s Hospital at Vanderbilt (Tennessee), Medical University of South Carolina Children’s Health (South Carolina), Texas Children’s Hospital (Texas), Holtz Children’s Hospital (Florida), Children’s Hospital of New Orleans (Louisiana), West: University of California San Francisco Benioff Children’s Hospital Oakland (California), Children’s Hospital Colorado (Colorado), Children’s Hospital Los Angeles (California), University of California San Diego-Rady Children’s Hospital (California).