Children are not little adults, as the saying goes in pediatrics. SARS-CoV-2 infection seemingly spared children compared with adults during the early wave of the pandemic. When children were infected, a smaller proportion had severe infections. On the basis of these 2 generalizations, many have inferred that children are at low risk for deleterious outcomes from COVID-19. This assumption raises the question of the utility of vaccinating children, especially the youngest children, who may have a vaccine authorized in the coming months. Rigorous epidemiologic studies on the pediatric population have been limited. However, Kubale et al1 used a cohort in which they studied prior viral infections, such as influenza, Zika virus, and dengue virus, to answer unresolved questions regarding SARS-CoV-2 infection in young children. The article provides needed data as regulatory agencies and parents weigh the risks and benefits of vaccinating the youngest children.
Three main questions should be asked when establishing the individual benefits of vaccination, in addition to potential societal advantages not discussed here. First, is the person at risk of contracting the disease? Kubale et al1 examined rates of both asymptomatic and symptomatic SARS-CoV-2 infection through molecular and antibody testing. The team prospectively studied nearly 2000 children younger than 14 years in Nicaragua. They identified that SARS-CoV-2 infected more than 50% of the children during the 18-month study, through the emergence of Gamma and Delta variants. Molecular testing of symptomatic children captured only 10% of infections during acute infection, and serologic surveys discovered the remaining cases. Of interest, children younger than 2 years had 16.1 cases per 100 person-years compared with 5.5 to 6.9 cases per 100 person-years in the older age groups. Directly extrapolating these findings to clinical populations in the US is difficult given the differences between the countries. Notably, the households in the study had a mean of 7.9 people compared with fewer than 3 in the US. However, these differences do not change the fact that SARS-CoV-2 infects young children when they are exposed. Available data on pediatric infections in the US confirm that children were infected at even higher rates than older adults during the Omicron surge, but the official tallies reported fewer cases in the youngest age group than older children.2 Kubale et al1 further subdivided the youngest ages compared with reports in the US and captured children who may not have sought testing in a health care setting. For example, data from the Centers for Disease Control and Prevention combine children from birth to 4 years and are limited by reporting mechanisms that may miss at-home antigen testing, a popular testing method during the Omicron surge.3 Taken together, these findings provide strong evidence that children, especially infants and toddlers, are susceptible to SARS-CoV-2 infection.
The second question to answer when determining whether a person needs immunization is the degree to which the individual is at risk for severe infection. Unfortunately, the study by Kubale et al1 was underpowered to make statistical conclusions regarding severity outcomes. However, they did find an increased rate of hospitalization in the youngest cohort. A recent systematic analysis4 of international prevaccine serologic studies modeled that the infection-fatality ratio increased in younger children with a nadir at 7 years of age before increasing again in adults. A study5 that examined outcomes of hospitalized children in the US found that children younger than 1 year were more likely to be hospitalized, but they were not at higher risk for severe infection compared with older age groups. Even during the Omicron surge, when vaccination did not necessarily prevent infection, immunization in older children protected against hospitalization.6 In addition to acute medical outcomes, SARS-CoV-2 infection puts children at risk for longer-term sequelae, such as multisystem inflammatory syndrome in children or long COVID, and nonmedical negative consequences, such as absence from childcare. In summary, although further research is needed to firmly establish the risk of severe outcomes, the youngest children are at risk for hospitalization and deleterious effects of infection regardless of whether this risk is higher than for other groups, and immunization can protect against those consequences.
Third, does acquired immunity provide durable protection from future infections? Kubale et al1 were able to capture reinfected children by following the same cohort across multiple viral surges. Surprisingly, symptomatic reinfection occurred in 20% of children with acute infections captured through molecular testing. Some have argued that prior infection protects from future infections, but these data argue against that for children, similar to adults. In addition, adult studies7 on vaccine effectiveness have demonstrated that vaccination after infection provides increased protection against subsequent infections compared with infection alone. Because pediatric vaccine studies have used similar immunologic end points as adult studies, presumably the findings will hold true for younger children.
Kubale et al1 provide clear data indicating that SARS-CoV-2 infects young children more so than older children, adding to the emerging evidence that the youngest children are at risk for hospitalization and negative outcomes after infection. Combined with studies in older children and adults demonstrating that vaccination can provide improved protection even after natural infection and can protect from hospitalization, immunization appears to be a reliable method to protect young children. With the upcoming release of vaccine safety data, regulators can perform a complete risk-benefit analysis, and much-needed protection for our youngest population may be possible.
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Article Information
Published: June 27, 2022. doi:10.1001/jamanetworkopen.2022.18801
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Heald-Sargent T. JAMA Network Open.
Corresponding Author: Taylor Heald-Sargent, MD, PhD, Ann and Robert H. Lurie Children’s Hospital of Chicago, Division of Infectious Diseases, Department of Pediatrics, Northwestern University, 225 E Chicago Ave, Box 20, Chicago, IL 60611 (thsargent@luriechildrens.org).
Conflict of Interest Disclosures: Dr Heald-Sargent reported that her institution serves as a site for clinical trials, including one for a pediatric messenger RNA vaccine against SARS-CoV-2.
References
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