Recommendations for the Use of the Moderna COVID-19 Vaccine in Children Aged 6 Months–5 Years and the Pfizer-BioNTech COVID-19 Vaccine in Children Aged 6 Months–4 Years
Data reviewed with the EtR Framework supported the use of COVID-19 vaccine in children aged 6 months–5 years. COVID-19 is a major public health problem among young children. As of June 12, 2022, approximately 2 million COVID-19 cases, 20,000 hospitalizations, and 200 deaths from COVID-19 have been reported among U.S. children aged 6 months–4 years (7,8). The SARS-CoV-2 Omicron variant emerged in the United States in December 2021 and led to the highest COVID-19 incidence, rates of COVID-19–associated emergency department visits and COVID-19–associated hospitalization among children aged 6 months–4 years yet seen during the pandemic (9). Approximately one half (51%–54%) of children aged 6 months–4 years with a COVID-19–associated hospitalization had no underlying health conditions, highlighting the risk for severe COVID-19 even among young children without underlying health conditions (9). During the period of Omicron predominance, illness among children aged 6 months–4 years with COVID-19–associated hospitalizations was as severe or more severe than that among children and adolescents aged 5–17 years, who were eligible for COVID-19 vaccination during that period (9). Furthermore, COVID-19 hospitalization rates among children aged 6 months–4 years during October 2021–April 2022 were as high or higher than were influenza-associated hospitalization rates during the 2017–18, 2018–19, and 2019–20 influenza seasons (10).
SARS-CoV-2 can also lead to complications after acute infection. MIS-C is a severe illness in persons aged <21 years that occurs 2–6 weeks after SARS-CoV-2 infection and is characterized by fever, multisystem organ involvement, and laboratory evidence of inflammation (11). As of May 31, 2022, CDC has received 8,525 reports of cases of MIS-C in the United States, including 69 deaths (12); children aged 6 months–4 years account for 1,990 (23%) of these cases and 9 (13%) of the deaths among MIS-C cases (9). Post–COVID-19 conditions, which include a range of new, returning, or ongoing, health problems occurring ≥4 weeks after acute SARS-CoV-2 infection, also occur in children, including those aged <5 years (13–15). However, evidence regarding the prevalence and spectrum of these conditions in children, especially young children, is limited by the inability of younger children to verbalize symptoms, few studies that include children, lack of appropriate control groups, and because symptoms similar to those seen in post–COVID-19 conditions are frequently reported among children without known SARS-CoV-2 infection (13,14,16).
The pandemic has also had additional indirect effects on children and families, including missed routine childhood immunizations and health care visits; worsening of children’s social, emotional, and mental well-being; and disruptions in early child care and education programs (17–19). In a survey conducted during July 15–August 2, 2021, 39% of parents reported that an adult in their household either left a job or changed work schedules to care for children during the past year; parents of a child aged <5 years, Black and African American parents, Hispanic or Latino parents, and parents with an annual household income of <$40,000 were most likely to report household job disruptions (20). COVID-19 vaccination in this age group may provide parents with increased confidence to return to prepandemic activities, improving social interactions in young children.
Implementation of these recommendations will require educating vaccine providers about the correct age-appropriate product (Table 1) and vaccination schedule (Table 2) for each vaccine, to avoid vaccine administration errors. ACIP determined that use of the Moderna and Pfizer-BioNTech COVID-19 vaccines among children is a reasonable and efficient allocation of resources. To expand COVID-19 vaccine access, additional considerations should be given to demographic groups that have experienced disproportionate COVID-19 morbidity and mortality, as well as those with barriers to routine health care (e.g., members of certain racial and ethnic groups and those living in a rural area, experiencing homelessness, or lacking health insurance). Children from racial and ethnic minority groups have experienced a disproportionately high incidence of COVID-19, associated hospitalization, and MIS-C (7,12,21). Pediatricians and health care providers remain the most trusted source among parents for information about COVID-19 vaccines for children (22). Based on the National Immunization Survey-Child COVID Module interviews conducted in May 2022, 33.5% of parents said they would definitely vaccinate their child aged 6 months–4 years for COVID-19, once eligible, and 19.6% said they would probably vaccinate their child aged 6 months–4 years (7). Thus, pediatricians and other primary care providers who care for children will be critical to increasing COVID-19 vaccine confidence among parents and coverage with COVID-19 vaccine among young children.
ACIP reviewed the balance of known and potential benefits and risks regarding the use of the Moderna COVID-19 vaccine in children aged 6 months–5 years and Pfizer-BioNTech COVID-19 vaccine in children aged 6 months–4 years, each compared with no vaccine. Both vaccines demonstrated ability to prevent COVID-19 and met noninferiority criteria based on immunobridging data. Although both the Moderna and Pfizer-BioNTech COVID-19 vaccine trials were conducted when Omicron was the predominant circulating SARS-CoV-2 variant, case accrual after the final dose occurred in different months, resulting in differences in COVID-19 incidence across the trials. Thus, efficacy estimates cannot be directly compared between these two vaccines. Moreover, vaccine efficacy from these trials should be interpreted in the context of what is known about vaccine effectiveness against Omicron infection. Postauthorization observational studies in persons aged ≥5 years have demonstrated that the vaccine effectiveness against Omicron infection is lower than that observed against earlier SARS-CoV-2 variants (23,24). However, postauthorization observational data also indicate that mRNA vaccine effectiveness is higher, even during Omicron predominance, against hospitalization (68% a median of 37 days after the second dose in children aged 5–11 years) than against infection (40% during the 2 months after the second dose in children aged 5–11 years) (25). Importantly, during Omicron predominance, mRNA vaccine effectiveness against MIS-C remained high (78%) among children aged 5–11 years (25). The clinical trials were not powered to detect efficacy against severe disease in young children, but similar patterns are expected in this age group to what has been observed in persons aged ≥5 years.
ACIP also considered evidence from known and potential harms from COVID-19 vaccines. Myocarditis and pericarditis are rare adverse events that have been reported after receipt of mRNA COVID-19 vaccines (26,27). Among vaccine recipients aged ≥5 years, the observed risk for myocarditis is highest among males aged 12–39 years (26,28,29). Cases of myocarditis among children aged 5–11 years after Pfizer-BioNTech COVID-19 vaccination have been rarely reported, primarily in boys and after dose 2 (28,29). To date, monitoring in CDC’s Vaccine Safety Datalink have not detected an increased risk for myocarditis and pericarditis in children aged 5–11 years (29). No cases of myocarditis occurred among 7,804 children aged 6 months–5 years in the Moderna and Pfizer-BioNTech COVID-19 vaccine clinical trials who received an mRNA vaccine and had ≥7 days of follow-up, although the trials were not adequately powered to detect rare adverse events. Postauthorization safety monitoring, including monitoring for myocarditis and pericarditis after mRNA COVID-19 vaccination, is conducted through multiple national safety surveillance systems.
ACIP determined that the benefits of COVID-19 vaccination outweigh the known and potential risks, even in the setting of high seroprevalence among young children; by April 2022, in a national sample of children aged 6 months–4 years, 71% had infection-induced SARS-CoV-2 antibodies (9). Past infection with SARS-CoV-2 provides some protection against reinfection, but the immune response to infection can vary, especially by disease severity, and might not provide broad protection against all SARS-CoV-2 variants (30). The Omicron-wave surges of pediatric COVID-19 hospitalizations occurred even in the setting of high seroprevalence, suggesting this alone is not sufficient to provide broad population-level protection. Vaccination in previously infected persons enhances protection against reinfection (30–32) and COVID-19–associated hospitalization, including infections and hospitalizations due to the Omicron variant (32,33). No concerns have been identified in postauthorization safety surveillance associated with vaccination of seropositive persons aged ≥5 years. After assessing the balance of benefits and risks for COVID-19 vaccination, ACIP made an interim recommendation for vaccination with the Moderna COVID-19 vaccine for children aged 6 months–5 years as a 2-dose primary series as authorized under the EUA and an interim recommendation for vaccination with the Pfizer-BioNTech COVID-19 vaccine for children aged 6 months–4 years as a 3-dose primary series as authorized under the EUA. ACIP does not state a product preference between the two recommended vaccines for children aged 6 months–5 years; children may receive any ACIP-recommended COVID-19 vaccine and are encouraged to receive the earliest vaccine available to them. Once a primary series is started, the same mRNA vaccine product should be used for all doses in the series.
The GRADE evidence profiles, which provide details on the identification and assessment of relevant evidence, are available for the Moderna COVID-19 vaccine at https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-moderna-vaccine-6-months-5-years.html and for the Pfizer-BioNTech COVID-19 vaccine at https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-pfizer-biontech-vaccine-6-months-4-years.html. The EtR supporting evidence for both the Moderna COVID-19 vaccine and the Pfizer-BioNTech COVID-19 vaccine is available at https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-moderna-pfizer-children-vaccine-etr.html. Additional clinical considerations, including recommendations for children who are moderately or severely immunocompromised, are available at https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html.
These interim recommendations and clinical considerations are based on use of the Moderna COVID-19 vaccine under an EUA and on the Pfizer-BioNTech COVID-19 vaccine under an EUA and might change as more evidence becomes available. COVID-19 vaccines must be administered according to applicable state and territorial vaccination laws. Before vaccination, the EUA Fact Sheet (available at https://www.fda.gov/media/159309/download for the Moderna COVID-19 vaccine and https://www.fda.gov/media/159313/download for the Pfizer-BioNTech COVID-19 vaccine) should be provided to parents or guardians. ACIP will continue to review additional data as they become available; updates to recommendations or clinical considerations will be posted on the ACIP website (https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html).