Safety of Third mRNA COVID-19 Vaccine Doses in Children Aged 6 Months to 5 Years

This page summarizes a CDC safety report covering doses given from June 17, 2022, to May 7, 2023, and the recommendations in force at that time. COVID-19 vaccine guidance has been updated since; check current CDC recommendations.

As of May 7, 2023, CDC's Advisory Committee on Immunization Practices recommended that every child aged 6 months to 5 years receive at least one age-appropriate bivalent mRNA COVID-19 vaccine dose, with more doses for some children depending on their vaccination history and whether they were immunocompromised. Earlier monitoring of the first doses in this age group had found that brief local and whole-body reactions were common and serious adverse events rare. This report looked at what happened after a third dose.

The two monitoring systems

• v-safe is CDC's voluntary smartphone-based system for tracking health after COVID-19 vaccination. From June 19, 2022, parents could enroll children aged 6 months to 4 years and answer daily surveys on their child's behalf during the week after each dose. A call center followed up with anyone reporting medical care.
• VAERS, the Vaccine Adverse Event Reporting System, is a passive system run jointly by CDC and the Food and Drug Administration (FDA). It takes reports from health care providers, manufacturers and the public. CDC physicians reviewed every serious report and every report that did not describe a vaccination error.

Over the study period, about 495,576 children aged 6 months to 4 years received a third dose of Pfizer-BioNTech vaccine and 63,919 children aged 6 months to 5 years received a third dose of Moderna vaccine.

What parents reported to v-safe

A third dose was recorded for 2,969 children in v-safe whose parents completed at least one health survey. Among them, 22.9% of Pfizer-BioNTech recipients and 6.2% of Moderna recipients got another vaccine at the same visit, most often an influenza vaccine.

• No reactions at all: 1,119 children (37.7%).
• Timing: reactions were most often reported on the day after vaccination.
• Local reactions at the injection site were reported for 19.9% of children aged 6 months to 2 years and 36.9% of those aged 3 to 4 years after Pfizer-BioNTech, and for 30.9% and 52.1% of children aged 6 months to 2 years and 3 to 5 years after Moderna.
• Systemic reactions were reported for 57.0% and 43.9% of the two Pfizer-BioNTech age groups, and 53.3% and 47.3% of the two Moderna age groups.
• Most common: irritability or crying, injection-site pain, sleepiness and fever among the youngest children; injection-site pain, fatigue and fever among those aged 3 to 5.
• Severity: most reactions were mild — noticeable but not a problem.

Parents of 211 children (7.1%) said that at some point in the week their child could not do normal daily activities, and 90 (3.0%) sought medical care, mostly at an outpatient clinic. One child was hospitalized, for pneumonia. Parents of 30 children said the care was unrelated to vaccination, and 34 of the 90 reports described signs of an infection such as cough, conjunctivitis or a hand-foot-and-mouth disease rash.

What VAERS received

VAERS processed 407 reports for young children after Pfizer-BioNTech and 129 after Moderna. Most (90.9%) involved a COVID-19 vaccine given on its own.

• Vaccination errors dominated. 420 reports (78.4%) described errors such as giving the wrong formulation, the wrong schedule, an expired product or an incorrect dose. Only 27 of these (5.0%) said the child had an adverse health event.
• Nonserious reports without an error numbered 108. The most common findings on review were infections (52.8%), no adverse event at all (12.0%) and rash (8.3%).
• Serious reports numbered eight (1.5%): acute hemorrhagic edema of infancy (with a non-SARS-CoV-2 coronavirus infection), diabetic ketoacidosis after new-onset type 1 diabetes, Henoch-Schönlein purpura, Kawasaki disease, two new-onset seizures without fever, pneumonia, and a viral flare of asthma. After review of all available information, no evidence suggested any of them were related to vaccination.

What it means

The findings matched those after first and second doses in this age group, and reactions were less frequent than those reported for children aged 5 to 11 after a booster. More than 98.0% of VAERS reports were nonserious. Errors in giving vaccines have made up a large share of reports for children generally — 85.0% of VAERS reports for children aged 5 to 11 after bivalent boosters — and the authors suggest that ACIP's simplified bivalent guidance might reduce them.

The authors note that although SARS-CoV-2 infection in young children is typically mild, it can cause serious illness, including multisystem inflammatory syndrome in children, long-term effects and death, and that mRNA vaccination protected children aged 3 to 5 against symptomatic infection for at least 4 months.

Limitations

• v-safe is voluntary, so its participants may not represent all vaccinated children.
• VAERS depends on people choosing to report, which brings reporting bias and underreporting, especially of nonserious events.
• Monovalent and bivalent formulations were combined, though findings in older children had not differed by formulation.
• The surveillance period was short and the number of vaccinated children small.

Sources

• Anne M. Hause, Paige Marquez, Bicheng Zhang, Pedro L. Moro, Tanya R. Myers, Colin Bradley, Samaneh Bazel, Sarada S. Panchanathan, Tom T. Shimabukuro and David K. Shay, "Safety Monitoring of mRNA COVID-19 Vaccine Third Doses Among Children Aged 6 Months–5 Years — United States, June 17, 2022–May 7, 2023," Morbidity and Mortality Weekly Report, CDC: https://www.cdc.gov/mmwr/volumes/72/wr/mm7223a2.htm
• The source gives two different totals for third doses administered; this page gives only the per-vaccine figures.