Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA Vaccination in Preventing COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Nonimmunocompromised Children and Adolescents Aged 5–1 – cdc.gov

The efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine against laboratory-confirmed COVID-19 exceeded 90% in clinical trials that included children and adolescents aged 5–11, 12–15, and 16–17 years (1–3). Limited real-world data on 2-dose mRNA vaccine effectiveness (VE) in persons aged 12–17 years (referred to as adolescents in this report) have also indicated high levels of protection against SARS-CoV-2 (the virus that causes COVID-19) infection and COVID-19–associated hospitalization (4–6); however, data on VE against the SARS-CoV-2 B.1.1.529 (Omicron) variant and duration of protection are limited. Pfizer-BioNTech VE data are not available for children aged 5–11 years. In partnership with CDC, the VISION Network* examined 39,217 emergency department (ED) and urgent care (UC) encounters and 1,699 hospitalizations^† among persons aged 5–17 years with COVID-19–like illness across 10 states during April 9, 2021–January 29, 2022,^§ to estimate VE using a case-control test-negative design. Among children aged 5–11 years, VE against laboratory-confirmed COVID-19–associated ED and UC encounters 14–67 days after dose 2 (the longest interval after dose 2 in this age group) was 46%. Among adolescents aged 12–15 and 16–17 years, VE 14–149 days after dose 2 was 83% and 76%, respectively; VE ≥150 days after dose 2 was 38% and 46%, respectively. Among adolescents aged 16–17 years, VE increased to 86% ≥7 days after dose 3 (booster dose). VE against COVID-19–associated ED and UC encounters was substantially lower during the Omicron predominant period than the B.1.617.2 (Delta) predominant period among adolescents aged 12–17 years, with no significant protection ≥150 days after dose 2 during Omicron predominance. However, in adolescents aged 16–17 years, VE during the Omicron predominant period increased to 81% ≥7 days after a third booster dose. During the full study period, including pre-Delta, Delta, and Omicron predominant periods, VE against laboratory-confirmed COVID-19–associated hospitalization among children aged 5–11 years was 74% 14–67 days after dose 2, with wide CIs that included zero. Among adolescents aged 12–15 and 16–17 years, VE 14–149 days after dose 2 was 92% and 94%, respectively; VE ≥150 days after dose 2 was 73% and 88%, respectively. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations, including a booster dose for those aged 12–17 years.

VISION Network VE methods have been previously published (7). In brief, eligible medical encounters were defined as ED and UC encounters and hospitalizations among persons aged ≥5 years with a COVID-19–like illness diagnosis^¶ who had received SARS-CoV-2 molecular testing (primarily by reverse transcription–polymerase chain reaction assay) during the 14 days before through 72 hours after the encounter. For adolescents aged 16–17 years, the study period began when COVID-19 vaccines were recommended and became available to persons aged ≥16 years at each study site (April–May 2021).** For children aged 5–11 years and adolescents aged 12–15 years, the study period began 5 weeks after the Pfizer-BioNTech vaccine was recommended for their age group.^†† The dates when the Delta and Omicron variants became predominant (accounted for >50% of sequenced viruses) were determined for each study site based on state and national surveillance data.^§§ Patients were excluded if they 1) were vaccinated before the CDC recommendation date for their age group, 2) received a third dose before booster doses were recommended for their age group, 3) received a booster dose <5 months after dose 2, 4) received 1 or >3 doses of the vaccine, or 5) if <14 days had elapsed since receipt of dose 2 or <7 days since dose 3. Patients who were likely immunocompromised based on diagnosis codes were also excluded.^¶¶ VE was estimated using a case-control test-negative design comparing the odds of a positive SARS-CoV-2 test result between vaccinated (received 2 doses ≥14 days earlier or 3 doses ≥7 days earlier) and unvaccinated (received no doses) patients using multivariable logistic regression models*** (7). VE was not calculated for exposure categories with fewer than 20 encounters or with no SARS-CoV-2 test–positive cases. A statistically significant difference in VE or distributions of vaccination or infection status was indicated by nonoverlapping 95% CIs or standardized mean or proportion differences ≥0.2. All statistical analyses were conducted using R software (version 4.1.2; R Foundation). This study was reviewed and approved by the institutional review boards at participating sites or under a reliance agreement with the Westat, Inc. institutional review board.^†††

¹Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California Division of Research, Oakland, California; ²Division of Child and Adolescent Health, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York; ³Department of Population and Family Health, Columbia University Mailman School of Public Health, New York, New York; ⁴NewYork-Presbyterian Hospital, New York, New York; ⁵Westat, Rockville, Maryland; ⁶Baylor Scott & White Health, Temple, Texas; ⁷Texas A&M University College of Medicine, Temple, Texas; ⁸Children’s Minnesota, Minneapolis, Minnesota; ⁹Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon; ¹⁰Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado; ¹¹Center for Biomedical Informatics, Regenstrief Institute, Indianapolis, Indiana; ¹²Indiana University School of Medicine, Indianapolis, Indiana; ¹³Division of Infectious Diseases and Clinical Epidemiology, Intermountain Healthcare, Salt Lake City, Utah; ¹⁴CDC COVID-19 Emergency Response Team; ¹⁵HealthPartners Institute, Minneapolis, Minnesota; ¹⁶Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana; ¹⁷Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York;¹⁸Regenstrief Institute, Indianapolis, Indiana; ¹⁹Vanderbilt University Medical Center, Nashville, Tennessee.

References

1. Walter EB, Talaat KR, Sabharwal C, et al.; C4591007 Clinical Trial Group. Evaluation of the BNT162b2 Covid-19 vaccine in children 5 to 11 years of age. N Engl J Med 2022;386:35–46. https://doi.org/10.1056/NEJMoa2116298external icon PMID:34752019external icon
2. Frenck RW Jr, Klein NP, Kitchin N, et al.; C4591001 Clinical Trial Group. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med 2021;385:239–50. https://doi.org/10.1056/NEJMoa2107456external icon PMID:34043894external icon
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Abbreviations: ED = emergency department; ICD-9 = International Classification of Diseases, Ninth Revision; ICD-10 = International Classification of Diseases, Tenth Revision; SMD = standardized mean or proportion difference; UC = urgent care.
* Medical events with an encounter or discharge code consistent with COVID-19–like illness were included, using ICD-9 and ICD-10. Four categories of codes were considered: 1) acute respiratory illness, including COVID-19, respiratory failure, viral or bacterial pneumonia, asthma exacerbation, influenza, and viral illness not otherwise specified; 2) nonrespiratory COVID-19–like illness diagnoses including cause-unspecified gastroenteritis, thrombosis, and acute myocarditis; 3) respiratory signs and symptoms consistent with COVID-19–like illness, including hemoptysis, cough, dyspnea, painful respiration, or hypoxemia; and 4) signs and symptoms of acute febrile illness. One code in any of the four categories was sufficient for inclusion. Clinician-ordered molecular assays (e.g., real-time reverse transcription–polymerase chain reaction) for SARS-CoV-2 occurring ≤14 days before to <72 hours after the encounter date were included.
^† Vaccination was defined as having received the listed number of doses of COVID-19 Pfizer-BioNTech BNT162b2 vaccine ≥14 days (for 2 doses) or ≥7 days (for 3 doses) before the medical event index date, which was the date of respiratory specimen collection associated with the most recent positive or negative SARS-CoV-2 test result before medical event or the admission date if testing only occurred after the admission.
^§ Partners contributing data on medical events were in California (vaccine availability: April 30, 2021), Colorado (May 22, 2021), Indiana (April 27, 2021), Minnesota and Wisconsin (April 21, 2021), New York (April 27, 2021), Oregon and Washington (April 28, 2021), Texas (March 29, 2021), Utah (April 9, 2021). The study period began in September 2021 for partners located in Texas. For adolescents aged 16–17 years, the study period began when COVID-19 vaccines became available to all persons aged ≥16 years at each study site. For children aged 5–11 and persons aged 12–15 years, the study period began 5 weeks after the Pfizer-BioNTech vaccine was authorized for each age group (November 2, 2021, and May 12, 2021, respectively).
^¶ An absolute SMD ≥0.20 indicates a nonnegligible difference in variable distributions between medical events for vaccinated versus unvaccinated patients; single SMD calculated by averaging pairwise comparisons of each vaccinated category versus unvaccinated and separately for patients with SARS-CoV-2–positive versus SARS-CoV-2–negative test results. For example, the age SMD calculation comparing unvaccinated versus different vaccinated categories was generated by averaging the pairwise SMD calculations for unvaccinated and 2 doses (14–149 days earlier), unvaccinated and 2 doses (≥150 days earlier), and unvaccinated and 3 doses (≥7 days earlier). In addition, the age SMD calculation comparing negative SARS-CoV-2 test result and positive SARS-CoV-2 test result was generated by directly calculating the SMD for negative SARS-CoV-2 test result and positive SARS-CoV-2 test result.
** Estimated date of Delta and Omicron predominance at contributing sites: California (Delta: June 23, 2021; Omicron: December 21, 2021); Colorado (Delta: June 3, 2021; Omicron: December 19, 2021); Indiana (Delta: June 23, 2021; Omicron: December 26, 2021); Minnesota and Wisconsin (Delta: June 28, 2021; Omicron: December 25, 2021); New York (Delta: June 30, 2021; Omicron: December 18, 2021); Oregon and Washington (Delta: June 30, 2021; Omicron: December 24, 2021); Texas (Delta: July 3, 2021; Omicron: December 16, 2021); Utah (Delta: June 1, 2021; Omicron December 24, 2021). Pre-Delta refers to the period before Delta predominance.
^†† Indicates the reference group used for standardized mean or proportion difference calculations for dichotomous variables.
^§§ Other race includes Asian, Native Hawaiian or other Pacific islander, American Indian or Alaska Native, Other not listed, and multiple races.
^¶¶ Chronic respiratory condition was defined as the presence of discharge code for asthma, sleep apnea, or other lung disease using ICD-9 and ICD-10 diagnosis codes.
*** Chronic nonrespiratory condition was defined as the presence of discharge code for heart failure, ischemic heart disease, hypertension, other heart disease, stroke, other cerebrovascular disease, diabetes type I or II, other diabetes, metabolic disease, clinical obesity, clinically underweight, renal disease, liver disease, blood disorder, immunosuppression, organ transplant, cancer, neurologic disorder, musculoskeletal disorder, Down Syndrome, congenital heart disease, neurologic conditions, muscular dystrophy, sickle cell disease, prematurity (<24 weeks), developmental delay, technology dependence, or chronic gastrointestinal disease/irritable bowel syndrome.

Abbreviations: ED = emergency department; NC = not calculated; Ref = referent group; UC = urgent care; VE = vaccine effectiveness.
* VE was calculated as [1 − odds ratio] x 100%, estimated using a test-negative design, adjusted for age, geographic region, calendar time (days since January 1, 2021), and local virus circulation (percentage of SARS-CoV-2–positive results from testing within the counties surrounding the facility on the date of the encounter) and weighted for inverse propensity to be vaccinated or unvaccinated. Generalized boosted regression trees were used to estimate the propensity to be vaccinated based on sociodemographic characteristics, underlying medical conditions, and facility characteristics.
^† Medical events with an encounter or discharge code consistent with COVID-19–like illness were included, using International Classification of Disease, Ninth Revision and International Classification of Diseases, Tenth Revision. Four categories of codes were considered: 1) acute respiratory illness, including COVID-19, respiratory failure, viral or bacterial pneumonia, asthma exacerbation, influenza, and viral illness not otherwise specified; 2) nonrespiratory COVID-19–like illness diagnoses including cause-unspecified gastroenteritis, thrombosis, and acute myocarditis; 3) respiratory signs and symptoms consistent with COVID-19–like illness, including hemoptysis, cough, dyspnea, painful respiration, or hypoxemia; and 4) signs and symptoms of acute febrile illness. One code in any of the four categories was sufficient for inclusion. Clinician-ordered molecular assays (e.g., real-time reverse transcription–polymerase chain reaction) for SARS-CoV-2 occurring ≤14 days before to <72 hours after the encounter date were included.
^§ Vaccination was defined as having received the listed number of doses of an mRNA-based COVID-19 Pfizer-BioNTech vaccine ≥14 days (for 2 doses) or ≥7 days (for 3 doses) before the medical event index date, which was the date of respiratory specimen collection associated with the most recent positive or negative SARS-CoV-2 test result before medical event or the admission date if testing only occurred after the admission.
^¶ Partners contributing data on medical events were in California (vaccine availability: April 30, 2021), Colorado (May 22, 2021), Indiana (April 27, 2021), Minnesota and Wisconsin (April 21, 2021), New York (April 27, 2021), Oregon and Washington (April 28, 2021), Texas (March 29, 2021), Utah (April 9, 2021). The study period began in September 2021 for partners located in Texas. For adolescents aged 16–17 years, the study period began when COVID-19 vaccines became available to all those aged ≥16 years at each study site. For children aged 5–11 and persons aged 12–15 years, the study period began 5 weeks after the Pfizer-BioNTech vaccine was authorized for each age group (November 2, 2021, and May 12, 2021, respectively).
** VE during the period of Delta predominance was not calculated for children aged 5–11 years because of the short eligibility interval in this age group during that time.
^†† Estimated date of Delta and Omicron predominance at contributing sites: California (Delta: June 23, 2021; Omicron: December 21, 2021); Colorado (Delta: June 3, 2021; Omicron: December 19, 2021); Indiana (Delta: June 23, 2021; Omicron: December 26, 2021); Minnesota and Wisconsin (Delta: June 28, 2021; Omicron: December 25, 2021); New York (Delta: June 30, 2021; Omicron: December 18, 2021); Oregon and Washington (Delta: June 30, 2021; Omicron: December 24, 2021); Texas (Delta: July 3, 2021; Omicron: December 16, 2021); Utah (Delta: June 1, 2021; Omicron December 24, 2021).

Abbreviations: ICD-9 = International Classification of Diseases, Ninth Revision; ICD-10 = International Classification of Diseases, Tenth Revision; SMD = standardized mean or proportion difference.
* Medical events with an encounter or discharge code consistent with COVID-19–like illness were included, using ICD-9 and ICD-10. Four categories of codes were considered: 1) acute respiratory illness, including COVID-19, respiratory failure, viral or bacterial pneumonia, asthma exacerbation, influenza, and viral illness not otherwise specified; 2) nonrespiratory COVID-19–like illness diagnoses including cause-unspecified gastroenteritis, thrombosis, and acute myocarditis; 3) respiratory signs and symptoms consistent with COVID-19–like illness, including hemoptysis, cough, dyspnea, painful respiration, or hypoxemia; and 4) signs and symptoms of acute febrile illness. One code in any of the four categories was sufficient for inclusion. Clinician-ordered molecular assays (e.g., real-time reverse transcription–polymerase chain reaction) for SARS-CoV-2 occurring ≤14 days before to <72 hours after the encounter date were included.
^† Vaccination was defined as having received the listed number of doses of COVID-19 Pfizer-BioNTech vaccine ≥14 days (for 2 doses) or ≥7 days (for 3 doses) before the medical event index date, which was the date of respiratory specimen collection associated with the most recent positive or negative SARS-CoV-2 test result before medical event or the admission date if testing only occurred after the admission.
^§ Partners contributing data on medical events were in California (vaccine availability: April 30, 2021), Colorado (May 22, 2021), Indiana (April 27, 2021), Minnesota and Wisconsin (April 21, 2021), New York (April 27, 2021), Oregon and Washington (April 28, 2021), Texas (March 29, 2021), Utah (April 9, 2021). The study period began in September 2021 for partners located in Texas. For adolescents aged 16–17 years, the study period began when COVID-19 vaccines became available to all those aged ≥16 years at each study site. For children aged 5–11 and persons aged 12–15 years, the study period began 5 weeks after the Pfizer-BioNTech vaccine was authorized for each age group (November 2, 2021, and May 12, 2021, respectively).
^¶ An absolute SMD ≥0.20 indicates a nonnegligible difference in variable distributions between medical events for vaccinated versus unvaccinated patients; single SMD calculated by averaging pair-wise comparisons of each vaccinated category versus unvaccinated and separately for patients with SARS-CoV-2–positive versus SARS-CoV-2–negative test results. For example, the age SMD calculation comparing unvaccinated versus different vaccinated categories was generated by averaging the pairwise SMD calculations for unvaccinated and 2 doses (14–149 days earlier), unvaccinated and 2 doses (≥150 days earlier), and unvaccinated and 3 doses (≥7 days). In addition, the age SMD calculation comparing negative SARS-CoV-2 test result and positive SARS-CoV-2 test result was generated by directly calculating the SMD for negative SARS-CoV-2 test result and positive SARS-CoV-2 test result.
** Estimated date of Delta and Omicron predominance at contributing sites: California (Delta: June 23, 2021; Omicron: December 21, 2021); Colorado (Delta: June 3, 2021; Omicron: December 19, 2021); Indiana (Delta: June 23, 2021; Omicron: December 26, 2021); Minnesota and Wisconsin (Delta: June 28, 2021; Omicron: December 25, 2021); New York (Delta: June 30, 2021; Omicron: December 18, 2021); Oregon and Washington (Delta: June 30, 2021; Omicron: December 24, 2021); Texas (Delta: July 3, 2021; Omicron: December 16, 2021); Utah (Delta: June 1, 2021; Omicron December 24, 2021). Pre-Delta refers to the period before Delta predominance.
^†† Indicates the reference group used for SMD calculations for dichotomous variables.
^§§ Other race includes Asian, Native Hawaiian or other Pacific islander, American Indian or Alaska Native, Other not listed, and multiple races.
^¶¶ Chronic respiratory condition was defined as the presence of discharge code for asthma, sleep apnea, or other lung disease using ICD-9 and ICD-10 diagnosis codes.
*** Chronic nonrespiratory condition was defined as the presence of discharge code for heart failure, ischemic heart disease, hypertension, other heart disease, stroke, other cerebrovascular disease, diabetes type I or II, other diabetes, metabolic disease, clinical obesity, clinically underweight, renal disease, liver disease, blood disorder, immunosuppression, organ transplant, cancer, neurologic disorder, musculoskeletal disorder, Down Syndrome, congenital heart disease, neurologic conditions, muscular dystrophy, sickle cell disease, prematurity (<24 weeks), developmental delay, technology dependence, or chronic gastrointestinal disease/irritable bowel syndrome.