Evaluating the Effectiveness of Monovalent COVID-19 Vaccines in Children and Adolescents


Study by the Centers for Disease Control and Prevention (CDC) explores future directions for pediatric COVID-19 vaccination amid emerging variants.

Young girl being vaccinated against COVID-19.

Image Credits: Unsplash

Young girl being vaccinated against COVID-19.

Image Credits: Unsplash

Pediatric COVID-19 vaccination effectively prevents COVID–19–related hospitalizations. Still, the protective duration of the original monovalent vaccine during the SARS-CoV-2 Omicron predominance needs further evaluation, especially considering the low coverage with updated COVID-19 vaccines.

Most case patients, who tested positive for SARS-CoV-2, were unvaccinated, despite frequently reported underlying conditions associated with severe COVID-19. The vaccine effectiveness (VE) of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%–66%) when the most recent dose was administered less than 120 days before hospitalization, and 19% (95% CI = 2%–32%) if the interval was between 120 and 364 days.

“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,” according to the CDC. 1

3 Key Takeaways

  1. The original monovalent mRNA COVID-19 vaccines are effective in decreasing hospitalization and critical illness related to COVID-19 among children and adolescents aged 5–18 years.
  2. The vaccine's effectiveness diminishes over time, showing higher protection (52% effectiveness) when administered less than 120 days before hospitalization compared to a longer interval (19% effectiveness between 120 and 364 days).
  3. The ongoing assessment of new and variant-containing vaccines, like the modified mRNA-1273.214, shows promise in fighting against evolving strains of SARS-CoV-2, particularly against variants like Delta and Omicron.

From December 19, 2021, to October 29, 2023, the Overcoming COVID-19 Network assessed the VE of 2 or more doses of the original monovalent COVID-19 mRNA vaccine in preventing COVID-19-related hospitalization and critical illness among US children and adolescents aged 5–18 years. The number of children and adolescents who received the bivalent or updated monovalent vaccines was too low to evaluate their effectiveness separately.

VE against critical COVID-19-related illness—defined as the need for noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, or illnesses resulting in death—was 57% (95% CI = 21%–76%) when the most recent dose was received less than 120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received between 120 and 364 days prior, and 38% (95% CI = 15%–55%) if the last dose was administered at any time within the previous year. VE remained consistent even after excluding children and adolescents with documented immunocompromising conditions.

The report has 4 main limitations, it did not assess immunity from previous SARS-CoV-2 infections which could affect observed VE due to increased seroprevalence after Omicron BA.1 emergence. Insufficient viral sequencing data hindered the analysis of immune evasion by specific subvariants. The low uptake of bivalent and updated monovalent vaccines made it impossible to estimate their VE. Finally, the findings may not be widely applicable since less than 20% of the case patients were previously healthy.

In a previous study published by Contagion focusing on the vaccine's safety, efficacy, and immune response in children aged 6 months to 11 years, particularly against the delta and omicron variants, the introduction of the modified mRNA-1273.214 version marks an advancement in fighting against the evolving SARS-CoV-2 strains.

“These findings are among the first to demonstrate the safety and inferred effectiveness based on immunobinding of a variant-containing COVID-19 vaccine in pediatric populations and support a 2-dose schedule for previously unvaccinated children with an additional dose when the formulation is successively updated,” according to investigators. “Further studies are needed to assess the effectiveness and durability of variant-containing COVID-19 vaccines in children.”2

In conclusion, due to the low frequency of children who received updated COVID-19 vaccines and the 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.


  1. CDC. Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron–Associated Hospitalization in Children and Adolescents — United States, 2021–2023. Morbidity and Mortality Weekly Report (MMWR). Published April 18, 2024. Accessed April 22, 2024. https://www.cdc.gov/mmwr/volumes/73/wr/mm7315a2.htm?s_cid=mm7315a2_w
  2. Abene, S. The Role of Moderna's Modified mRNA-1273.214 Vaccine in Children Against COVID-19. Contagion. Published March 22, 2024. Accessed April 22, 2024. https://www.contagionlive.com/view/the-role-of-moderna-s-modified-mrna-1273-214-vaccine-in-children-against-covid-19
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