Photo credit: DiasporaEngager (www.DiasporaEngager.com).

Laura D. Zambrano, PhD1; Margaret M. Newhams, MPH2; Regina M. Simeone, PhD1; Amanda B. Payne, PhD1; Michael Wu, MSc1; Amber O. Orzel-Lockwood, MPH2; Natasha B. Halasa, MD3; Jemima M. Calixte, MS2; Pia S. Pannaraj, MD4,5; Kanokporn Mongkolrattanothai, MD6; Julie A. Boom, MD7; Leila C. Sahni, PhD7; Satoshi Kamidani, MD, PhD8,9; Kathleen Chiotos, MD10; Melissa A. Cameron, MD11; Aline B. Maddux, MD12,13; Katherine Irby, MD14; Jennifer E. Schuster, MD15; Elizabeth H. Mack, MD16; Austin Biggs, MD16; Bria M. Coates, MD17,18; Kelly N. Michelson, MD17,18; Katherine E. Bline, MD19; Ryan A. Nofziger, MD20; Hillary Crandall, MD, PhD21,22; Charlotte V. Hobbs, MD23; Shira J. Gertz, MD24; Sabrina M. Heidemann, MD25; Tamara T. Bradford, MD26,27; Tracie C. Walker, MD28; Stephanie P. Schwartz, MD28; Mary Allen Staat, MD29; Samina S. Bhumbra, MD30; Janet R. Hume, MD31; Michele Kong, MD32; Melissa S. Stockwell, MD33,34,35; Thomas J. Connors, MD35,36; Melissa L. Cullimore, MD37; Heidi R. Flori, MD38; Emily R. Levy, MD39; Natalie Z. Cvijanovich, MD40; Matt S. Zinter, MD41; Mia Maamari, MD42; Cindy Bowens, MD42; Danielle M. Zerr, MD43; Judith A. Guzman-Cottrill, DO44; Ivan Gonzalez, MD45; Angela P. Campbell, MD1,*; Adrienne G. Randolph, MD2,46,47,*; Overcoming COVID-19 Investigators (View author affiliations)

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Summary

What is already known about this topic?

COVID-19 vaccination was shown to be effective against pediatric COVID-19 hospitalization before the emergence of the Omicron variant.

What is added by this report?

During December 19, 2021–October 29, 2023, receipt of ≥2 doses of an original monovalent mRNA COVID-19 vaccine was 52% effective against pediatric COVID-19 hospitalization and 57% effective against critical illness related to COVID-19, when the last dose was received within the 4 months preceding hospitalization, but protection decreased over time.

What are the implications for public health practice?

These findings support existing recommendations that children and adolescents aged 5–18 years remain up to date with COVID-19 vaccination given low vaccination coverage and waning effectiveness over time against COVID-19–related hospitalizations.

Abstract

Pediatric COVID-19 vaccination is effective in preventing COVID-19–related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021–October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19–related hospitalization and critical illness among U.S. children and adolescents aged 5–18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19–related hospitalizations was 52% (95% CI = 33%–66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%–32%) if the interval was 120–364 days. VE of the original monovalent vaccine against COVID-19–related hospitalization was 31% (95% CI = 18%–43%) if the last dose was received any time within the previous year. VE against critical COVID-19–related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%–76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = –9% to 49%) if it was received 120–364 days before hospitalization, and 38% (95% CI = 15%–55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.

Introduction

mRNA COVID-19 vaccines have been recommended for U.S. children and adolescents aged ≥5 years since November 2021† (1). Two doses of Pfizer-BioNTech (BNT162b2) vaccine protected against COVID-19–related hospitalizations before and after emergence of the SARS-CoV-2 Delta variant (2,3). Throughout Omicron variant predominance (beginning in December 2021), estimated pediatric COVID-19 vaccine effectiveness (VE) of the original monovalent vaccine was lower (2,4). This analysis evaluated durability of effectiveness of original monovalent vaccines, which were only available before September 2022, against COVID-19–related hospitalization among children and adolescents aged 5–18 years during December 19, 2021–October 29, 2023, when the SARS-CoV-2 Omicron variant predominated.

Methods

Study Participants

VE of ≥2 original monovalent COVID-19 vaccine doses§ against COVID-19–related hospitalizations (December 19, 2021–October 29, 2023) across 34 Overcoming COVID-19 Network sites** was evaluated using a case-control design according to previously described methods (2,3). Case-patients were children and adolescents aged 5–18 years who were hospitalized for acute COVID-19 and received a positive SARS-CoV-2 test result.†† Control patients hospitalized for COVID-19–like illness were matched to case-patients by site, age group, and admission date, but received a negative SARS-CoV-2 test result.§§ Critical COVID-19–related illness was defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death. Children and adolescents were a priori excluded from the analysis if they 1) received their most recent dose ≥365 days before hospitalization, 2) had an incomplete COVID-19 mRNA primary vaccination series, 3) had a COVID-19 hospitalization within the preceding 60 days, 4) had an unverifiable vaccination status, or 5) received a positive influenza test result.¶¶ Given subsequent findings of low (3%) bivalent vaccination coverage and no reported receipt of updated (2023–2024 formula) monovalent doses, children who received updated formulations were post hoc excluded from VE analyses.

Statistical Analysis and Vaccine Effectiveness Estimation

Bivariate associations between sociodemographic factors and both case or control status and vaccination status among case- and control patients were assessed using chi-square tests for binomial or categorical variables or Wilcoxon rank-sum tests for continuous variables. VE was estimated among all hospitalized patients and among patients without documented immunocompromising conditions*** and calculated as (1 − adjusted odds ratio) × 100% by time between last vaccine dose and hospitalization and by age,††† using multivariable logistic regression,§§§ including hospital site as a repeated effect using generalized estimating equations, and adjusting for the presence of one or more underlying medical condition, age (in years), month and year of hospitalization, U.S. Census Bureau region of hospital, social vulnerability index (SVI; i.e., continuous ranging from 0–1, with higher scores indicating increased vulnerability), and race and ethnicity. SAS software (version 9.4; SAS Institute) was used to conduct all analyses. This activity was reviewed by CDC, deemed not research, and conducted consistent with applicable federal law and CDC policy.¶¶¶

Results

Characteristics of Enrolled Population

During December 19, 2021–October 29, 2023, a total of 3,348 patients were enrolled, including 1,551 (46%) case-patients and 1,797 (54%) control patients.**** Only 3% of case-patients and of control patients had received bivalent COVID-19 vaccine, and none reported receipt of an updated monovalent dose; therefore, VE for these specific formulations could not be estimated. Case- and control patients were similar in age, sex, hospital U.S. Census Bureau region,†††† presence of any underlying respiratory condition (e.g., asthma or chronic lung disease), and clinical support received (Table 1). The presence of at least one underlying health condition was more common among case-patients (82%) than among control patients (73%) (p-value <0.001). Critical illness occurred in 294 (19%) case-patients and 322 (18%) control patients (p = 0.43). Patients living in lower SVI areas were more frequently vaccinated (Table 2).

Vaccine Effectiveness

VE of original monovalent mRNA COVID-19 vaccines against COVID-19–related hospitalization was 52% (95% CI = 33–66) when the most recent vaccine dose was received 7–119 days before hospitalization, 19% (95% CI = 2–32) when it was received 120–364 days before hospitalization, and 31% (95% CI = 18–43) if the last dose was received any time within the previous year. VE against critical COVID-19–related illness was 57% (95% CI = 21–76) when the last dose was 7–119 days before hospitalization, not significant when it was received 120–364 days before hospitalization, and 38% (95% CI = 15–55) when the most recent dose was received at any point within the previous year. During the peak of pediatric COVID-19 hospitalizations (December 19, 2021–March 19, 2022), VE was 55% (95% CI = 38–67) against COVID-19–related hospitalizations when the last dose was received a median of 129 days before hospitalization (IQR = 47–198 days) and 79% (95% CI = 59–89) against critical COVID-19–related illness when the last dose was received a median of 132 days before hospitalization (IQR = 46–215) (Supplementary Table, https://stacks.cdc.gov/view/cdc/152988). Estimates were similar after excluding children and adolescents with documented immunocompromising conditions (Table 3).

Discussion

During the period of SARS-CoV-2 Omicron predominance, receipt of ≥2 original monovalent COVID-19 vaccine doses was associated with fewer COVID-19–related hospitalizations in children and adolescents aged 5–18 years; however, protection from original vaccines was not sustained over time, necessitating increased coverage with updated vaccines. Most children and adolescents in this analysis who were hospitalized with COVID-19 were unvaccinated, and few had received updated vaccine doses despite a high prevalence of underlying comorbidities associated with more severe disease. Vaccination frequency declined with increasing social vulnerability, highlighting disparities in vaccination coverage comparable with published estimates from at least one other U.S. public health surveillance network (5). This finding might be driven by factors including vaccine hesitancy or barriers to accessing vaccines among more vulnerable populations (5).

VE of original monovalent doses against COVID-19–related pediatric hospitalizations was lower than previous VE estimates reported by the Overcoming COVID-19 Network before Omicron emergence (2). However, VE estimates from this report among children and adolescents hospitalized during December 19, 2021–March 19, 2022, were similar to previously published VE estimates from this network among children and adolescents hospitalized within the same date range (2). In a separate U.S. study of children and adolescents aged 5–15 years, VE against symptomatic SARS-CoV-2 infections was reported to wane in the months after a second dose, with improved VE observed after receipt of a booster dose (4). Effectiveness of bivalent vaccine formulations against pediatric hospitalizations was not estimable in this investigation; however, two recent studies report that receipt of a bivalent vaccine was associated with higher VE against symptomatic pediatric infections (6) and COVID-19–related hospitalizations in immunocompetent adults (7).

Limitations

The findings in this report are subject to at least four limitations. First, SARS-CoV-2 infection-induced immunity was not assessed (8); increased seroprevalence after Omicron BA.1 emergence (9) might have influenced observed VE. Second, limited viral sequencing data prevented consideration of subvariant-attributed immune evasion (10). Third, limited coverage with bivalent vaccines and currently recommended updated monovalent vaccines precluded the estimation of VE of these formulations. Finally, previously healthy children and adolescents accounted for <20% of case-patients, limiting generalizability.

Implications for Public Health Practice

Among approximately 1,500 children and adolescents aged 5–18 years with a COVID-19–related hospitalization, including nearly 300 with critical illness, original monovalent COVID-19 vaccines were associated with fewer hospitalizations, particularly within the first 4 months after vaccination. To address low coverage of updated vaccines and waning effectiveness of the original monovalent vaccine, children and adolescents should remain up to date with COVID-19 vaccination, including the current CDC recommendation for all persons aged ≥6 months to receive vaccination with updated (2023–2024) COVID-19 vaccines (1).

Overcoming COVID-19 Investigators

Meghan Murdock; Heather Kelley; Candice Colston; Ronald C. Sanders; Laura Miron; Masson Yates; Ashlyn Madding; Alexa Dixon; Michael Henne; Kathleen Sun; Jazmin Baez Maidana; Natalie Triester; Jaycee Jumarang; Daniel Hakimi; Kennis-Grace Mrotek; Liria Muriscot Niell; Natasha Baig; Elizabeth Temte; Lexi Petruccelli; Heidi Sauceda; Nicolette Gomez; Mark D. Gonzalez; Caroline R. Ciric; Jong-Ha C. Choi; Elizabeth G. Taylor; Grace X. Li; Nadine Baida; Heather E. Price; Mary Stumpf; Suden Kucukak; Eve Listerud; Maya Clark; Rylie Dittrich; Allison Zaff; Patrick Moran; Jessica C. Peterson; Noelle M. Drapeau; Lora Martin; Lacy Malloch; Maygan Martin; Cameron Sanders; Kayla Patterson; Melissa Sullivan; Shannon Pruitt; Elizabeth Ricciardi; Celibell Y. Vargas; Raul A. Silverio Francisco; Ana Valdez de Romero; Sheila Joshi; Merry Tomcany; Nicole Twinem; Chelsea C. Rohlfs; Amber Wolfe; Rebecca Douglas; Kathlyn Phengchomphet; Jenny Bush; Alanah Mckelvey; Mickael Boustany; Fatima A. Mohammed; Laura S. Stewart; Kailee Fernandez; Leenah Abojaib; Molly J. Kyles; Amanda Adler

1Coronavirus and Other Respiratory Viruses Division, National Center for Immunization and Respiratory Diseases, CDC; 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; 4Division of Infectious Diseases, Children’s Hospital Los Angeles, Los Angeles, California; 5Department of Pediatrics, University of California, San Diego, San Diego, California; 6Division of Pediatric Infectious Diseases, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, California; 7Department of Pediatrics, Baylor College of Medicine, Immunization Project, Texas Children’s Hospital, Houston, Texas; 8The Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Atlanta, Georgia; 9Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; 10Division of Critical Care Medicine, Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; 11Division of Pediatric Hospital Medicine, UC San Diego-Rady Children’s Hospital, San Diego, California; 12Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine, Aurora, Colorado; 13Children’s Hospital Colorado, Aurora, Colorado; 14Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children’s Hospital, Little Rock, Arkansas; 15Division of Pediatric Infectious Diseases, Department of Pediatrics, Children’s Mercy Kansas City, Kansas City, Missouri; 16Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina; 17Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois; 18Division of Critical Care Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois; 19Division of Pediatric Critical Care Medicine, Nationwide Children’s Hospital, Columbus, Ohio; 20Division of Critical Care Medicine, Department of Pediatrics, Akron Children’s Hospital, Akron, Ohio; 21Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, Utah; 22Primary Children’s Hospital, Salt Lake City, Utah; 23Department of Pediatrics, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi; 24Division of Pediatric Critical Care, Department of Pediatrics, Cooperman Barnabas Medical Center, Livingston, New Jersey; 25Division of Pediatric Critical Care Medicine, Children’s Hospital of Michigan, Central Michigan University, Detroit, Michigan; 26Department of Pediatrics, Division of Cardiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana; 27Children’s Hospital of New Orleans, New Orleans, Louisiana; 28Department of Pediatrics, University of North Carolina at Chapel Hill Children’s Hospital, Chapel Hill, North Carolina; 29Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; 30Ryan White Center for Pediatric Infectious Disease and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; 31Division of Pediatric Critical Care, University of Minnesota Masonic Children’s Hospital, Minneapolis, Minnesota; 32Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama; 33Division of Child and Adolescent Health, Department of Pediatrics, Vagelos College of Physicians and Surgeons, New York, New York; 34Department of Population and Family Health, Mailman School of Public Health Columbia University, New York, New York; 35New York-Presbyterian Morgan Stanley Children’s Hospital; New York, New York; 36Division of Critical Care and Hospital Medicine, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York; 37Division of Pediatric Critical Care, Department of Pediatrics, Children’s Nebraska, Omaha, Nebraska; 38Division of Pediatric Critical Care Medicine, Department of Pediatrics, C.S. Mott Children’s Hospital, Ann Arbor, Michigan; 39Divisions of Pediatric Infectious Diseases and Pediatric Critical Care Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota; 40Division of Critical Care Medicine, UCSF Benioff Children’s Hospital, Oakland, California; 41Department of Pediatrics, Divisions of Critical Care Medicine and Allergy, Immunology, and Bone Marrow Transplant, University of California San Francisco, San Francisco, California; 42Department of Pediatrics, Division of Critical Care Medicine, University of Texas Southwestern, Children’s Medical Center Dallas, Texas; 43Division of Pediatric Infectious Diseases, Department of Pediatrics, Seattle Children’s Hospital, Seattle, Washington; 44Department of Pediatrics, Division of Infectious Diseases, Oregon Health & Science University, Portland, Oregon; 45Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida; 46Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts; 47Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.

References

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TABLE 1. Characteristics of children and adolescents aged 5–18 years hospitalized with a COVID-19–like illness and a positive SARS-CoV-2 test result (case-patients) or a negative SARS-CoV-2 test result (control patients) — Overcoming COVID-19 Network, 34 pediatric hospitals, 26 states, December 19, 2021–October 29, 2023
Characteristic (no. with known information) No. (%) p-value*
Case-patients
(n = 1,551)		 Control patients
(n = 1,797)
Age group, yrs
5–11 853 (55) 1,042 (58) 0.08
12–18 698 (45) 755 (42)
Median age, yrs, IQR 11.3 (7.7–15.1) 10.5 (7.3–14.7) 0.01
Female sex 712 (46) 857 (48) 0.59
Race and ethnicity
Asian, non-Hispanic 71 (5) 41 (2) <0.001
Black or African American, non-Hispanic 403 (26) 438 (24)
White, non-Hispanic 571 (37) 675 (38)
Hispanic or Latino, any race 406 (26) 485 (27)
Multiple or other races, non-Hispanic 47 (3) 65 (4)
Unknown 53 (3) 93 (5)
Median social vulnerability index, IQR (3,345)† 0.58 (0.37–0.78) 0.57 (0.33–0.77) 0.10
U.S. Census Bureau region§
Northeast 253 (16) 272 (15) 0.35
Midwest 364 (23) 466 (26)
South 565 (36) 628 (35)
West 369 (24) 431 (24)
Circulating Omicron subvariant during hospitalization
Omicron BA.1/BA.1.1 638 (41) 776 (43) 0.23
Omicron BA.2/BA.4/BA.5/XBB.1.5/XBB.1.6 913 (59) 1021 (57)
Underlying health conditions
None 275 (18) 489 (27) <0.001
One or more 1,276 (82) 1,308 (73)
  Respiratory, including asthma 619 (40) 744 (41) 0.38
  Cardiac 235 (15) 172 (10) <0.001
  Neurologic or neuromuscular 524 (34) 352 (20) <0.001
  Immunocompromising conditions** 273 (18) 165 (9) <0.001
  Endocrine, including diabetes 195 (13) 181 (10) 0.02
  Multiple 526 (34) 382 (21) <0.001
COVID-19 vaccination status
Unvaccinated 1,137 (73) 1,210 (67) <0.001
Original monovalent dose, 7–119 days before hospitalization†† 94 (6) 207 (12)
Original monovalent dose, 120−364 days before hospitalization 277 (18) 322 (18)
Bivalent dose§§ 43 (3) 58 (3)
Clinical course
ICU admission (3,347) 404 (26) 500 (28) 0.25
Critical illness (3,343)¶¶ 294 (19) 322 (18) 0.43
Invasive mechanical ventilation 107 (7) 129 (7) 0.75
Noninvasive mechanical ventilation (BiPAP or CPAP) (3,347) 222 (14) 228 (13) 0.17
Vasoactive infusion 83 (5) 86 (5) 0.46
Extracorporeal membrane oxygenation 9 (1) 10 (1) 0.93
Died (3,343) 10 (1) 9 (1) 0.58
Median hospital days (IQR) (3,340) 4 (2–7) 4 (3–7) 0.79

Abbreviations: BiPAP = bilevel positive airway pressure; CPAP = continuous positive airway pressure; ICU = intensive care unit.
* Binomial or categorical variables were compared using chi-square tests of independence, and continuous variables were compared using Wilcoxon rank-sum tests.
† The social vulnerability index is a scale (range = 0–1), reflecting a composite score of socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation. A lower score indicates lower social vulnerability, whereas a higher score indicates higher social vulnerability, which might predispose a population to worse health outcomes. https://www.atsdr.cdc.gov/placeandhealth/svi
§ https://www2.census.gov/geo/pdfs/maps-data/maps/reference/us_regdiv.pdf

TABLE 2. Characteristics of COVID-19 case-patients and control patients with COVID-19–like illness, by vaccination status (N = 3,247) — Overcoming COVID-19 Network, 34 pediatric hospitals, 26 states, December 19, 2021–October 29, 2023
Characteristic (no. with known information if less than total N) COVID-19 vaccination status, no. (%)
Case-patients (n = 1,508)* Control patients (n = 1,739)†
Unvaccinated
(n = 1,137)		 Original monovalent dose, 7–364 d§
(n = 371)		 p-value Unvaccinated
(n = 1,210)		 Original monovalent dose, 7–364 d§
(n = 529)		 p-value
Median age, yrs (IQR) 10.1 (7.2–14.0) 14.4 (11.0–16.6) <0.001 9.3 (6.9–13.7) 13.3 (9.0–15.9) <0.001
Age group, yrs
5–11 718 (86) 114 (14) <0.001 806 (80) 207 (20) <0.001
12–18 419 (62) 257 (38) 404 (56) 322 (44)
Sex (3,246)**
Female 508 (74) 183 (26) 0.26 569 (68) 263 (32) 0.30
Male 628 (77) 188 (23) 641 (71) 266 (29)
Race and ethnicity
Asian, non-Hispanic 41 (59) 28 (41) 0.008 16 (40) 24 (60) <0.001
Black or African American, non-Hispanic 312 (79) 83 (21) 327 (77) 97 (23)
White, non-Hispanic 409 (73) 149 (27) 447 (69) 206 (32)
Hispanic or Latino, any race 301 (77) 89 (23) 310 (66) 163 (34)
Multiple or other races, non-Hispanic 37 (82) 8 (18) 50 (81) 12 (19)
Unknown 37 (73) 14 (27) 60 (69) 27 (31)
Median SVI (IQR) (3,244)†† 0.60 (0.38–0.79) 0.55 (0.32–0.76) 0.01 0.59 (0.38–0.78) 0.52 (0.26–0.76) <0.001
U.S. Census Bureau region§§
Northeast 154 (63) 91 (37) <0.001 143 (55) 118 (45) <0.001
Midwest 289 (82) 65 (18) 330 (73) 121 (27)
South 457 (82) 99 (18) 476 (78) 135 (22)
West 237 (67) 116 (33) 261 (63) 155 (37)
Underlying health conditions¶¶
None 214 (78) 59 (22) 0.20 342 (71) 138 (29) 0.35
One or more underlying condition 923 (75) 312 (25) 868 (69) 391 (31)
  Respiratory, including asthma 445 (75) 147 (25) 0.87 505 (71) 207 (29) 0.31
  Cardiac 156 (69) 71 (31) 0.01 103 (62) 63 (38) 0.03
  Neurologic or neuromuscular 379 (75) 127 (25) 0.75 207 (63) 122 (37) 0.004
  Immunocompromising conditions*** 188 (71) 76 (29) 0.08 99 (62) 61 (38) 0.03
  Endocrine, including diabetes 131 (71) 54 (29) 0.12 115 (66) 59 (34) 0.29
  Obesity 140 (75) 47 (25) 0.86 114 (67) 56 (33) 0.45
  Multiple 355 (71) 145 (29) 0.005 231 (64) 130 (36) 0.01

Abbreviations: d = days before hospitalization; SVI = social vulnerability index.
* This analysis excludes 43 of 1,551 case-patients who received a bivalent vaccine dose.
† This analysis excludes 58 of 1,797 control patients who received a bivalent vaccine dose.
§ All monovalent doses received before hospitalization were original monovalent vaccine doses directed against the original SARS-CoV-2 strain. No child or adolescent had received an updated (2023–2024 formula) monovalent vaccine dose, authorized on September 11, 2022, before hospitalization.
Binomial or categorical variables were compared using chi-square tests of independence and continuous variables were compared using Wilcoxon rank-sum tests.
** One unvaccinated case-patient had sex noted as “other” and was excluded from this comparison.
†† SVI is a scale (range = 0–1), reflecting a composite score of socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation. A lower score indicates lower social vulnerability, whereas a higher score indicates higher social vulnerability, which might predispose a population to worse health outcomes. https://www.atsdr.cdc.gov/placeandhealth/svi
§§ https://www2.census.gov/geo/pdfs/maps-data/maps/reference/us_regdiv.pdf

TABLE 3. Durability of effectiveness of original monovalent mRNA COVID-19 vaccination against hospitalization and critical illness for COVID-19 among pediatric patients aged 5–18 years, by age, vaccination timing, and patients without documented immunocompromising conditions — Overcoming COVID-19 Network, 34 pediatric hospitals, 26 states, December 19, 2021–October 29, 2023
Subgroup* No. vaccinated/Total no. (%) Interval from last vaccine dose to hospitalization, days, median (IQR) VE against COVID-19 hospitalization, % (95% CI)†
Case-patients Control patients
Hospitalizations among all patients
Any original monovalent dose 371/1,508 (25) 529/1,739 (30) 169 (86 to 237) 31 (18 to 43)
7–119 days since last dose 94/1,231 (8) 207/1,417 (15) 53 (32 to 86) 52 (33 to 66)
120–364 days since last dose 277/1,414 (20) 322/1,532 (21) 212 (169 to 275) 19 (2 to 32)
Any dose, ages 5–11 yrs 114/832 (14) 207/1,013 (20) 120 (46 to 224) 40 (22 to 53)
Any dose, ages 12–18 yrs 257/676 (38) 322/726 (44) 181 (121 to 245) 28 (6 to 44)
Hospitalizations among patients without documented immunocompromising conditions§,
Any original monovalent dose 295/1,244 (24) 468/1,579 (30) 173 (88 to 243) 34 (22 to 44)
7–119 days since last dose 62/1,011 (6) 183/1,294 (14) 53 (33 to 84) 61 (40 to 75)
120–364 days since last dose 233/1,182 (20) 285/1,396 (20) 213 (171 to 278) 17 (0 to 31)
Ages 5–11 yrs 84/684 (12) 191/933 (20) 120 (46 to 222) 48 (29 to 61)
Ages 12–18 yrs 211/560 (38) 277/646 (43) 187 (129 to 252) 23 (2 to 40)**
Critical illness†† among all patients
Any original monovalent dose 65/278 (23) 91/307 (30) 175 (79 to 253) 38 (15 to 55)
7–119 days since last dose 16/229 (7) 35/251 (14) 51 (36 to 74) 57 (21 to 76)§§
120–364 days since last dose 49/262 (19) 56/272 (21) 218 (172 to 287) 25 (–9 to 49)§§
Critical illness†† among patients without documented immunocompromising conditions§
Any original monovalent dose 59/253 (23) 85/288 (30) 171 (73 to 247) 36 (17 to 50)
7–119 days since last dose 13/207 (6) 34/237 (14) 51 (36 to 71) 63 (35 to 79)**
120–364 days since last dose 46/240 (19) 51/254 (20) 218 (170 to 287) 16 (–20 to 41)**,§§

Abbreviation: VE = vaccine effectiveness.
* All analyses excluded patients who received a bivalent vaccine dose (43 case-patients and 58 control patients). Models examining VE by time since last dose incorporated a three-level categorical predictor variable (unvaccinated, last monovalent dose 7–119 days before hospitalization, and last original monovalent dose 120 –364 days before hospitalization) to obtain VE estimates for each interval range. Models examining VE by age were stratified by age group (5–11 years and 12–18 years). All children who had received any original monovalent dose received their last dose within the previous year before hospitalization (<365 days).
† All models controlled for underlying medical condition, continuous age (in years), month and year of hospital admission, U.S. Census Bureau region, continuous social vulnerability index (range = 0–1), and race and ethnicity (categorized as non-Hispanic White, non-Hispanic Black or African-American, Hispanic or Latino, and other, multiple races, or unknown. Hospital site of enrollment was incorporated as a repeated effect.
§ This analysis excludes an additional 264 case-patients and 160 control patients who had documented immunocompromising conditions, yielding 1,244 case-patients and 1,579 control patients without any documented immunocompromising condition.
Immunocompromising conditions included active or previous oncologic disorder or immunosuppressive disorder (defined as solid organ transplant, HIV or AIDS, primary immunodeficiency, bone marrow transplant for nononcologic disease, or other disorder requiring treatment that suppresses the immune system).
** Where models did not converge, subvariant period (BA.1: December 19, 2021–March 19, 2022 and BA.2/BA.4/BA.5/XBB.1.5/XBB.1.6: March 20, 2022–October 29, 2023) was substituted as a covariate in place of month and year of hospital admission.
†† Critical illness was defined as illness resulting in noninvasive ventilation, invasive mechanical ventilation, receipt of vasoactive infusions, extracorporeal membrane oxygenation, or death. Both case-patients and control patients were required to have met this definition to be included in this subanalysis.
§§ Some estimates are imprecise (where 95% CIs were wider than 50%), which might be due to a relatively small number of persons in each level of vaccination or case status. This imprecision indicates that the actual VE could be substantially different from the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual could allow more precise interpretation.

Suggested citation for this article: Zambrano LD, Newhams MM, Simeone RM, et al. Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron–Associated Hospitalization in Children and Adolescents — United States, 2021–2023. MMWR Morb Mortal Wkly Rep 2024;73:330–338. DOI: http://dx.doi.org/10.15585/mmwr.mm7315a2


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