Prior Infection Does Not Protect Children Against Omicron

Since its emergence and rapid rise to dominance in late December 2021, the Omicron variant has caused unprecedented COVID-19 disease in children. This caused US health agencies, such as the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) to expedite data reviews and COVID-19 vaccine approvals for this vulnerable population.

Primary vaccination series, as well as booster doses, of Pfizer-BioNTech are now authorized for all children 5 years and older. However, some parents mistakenly believe having contracted an earlier strain of COVID-19 will protect children against Omicron. A recent study, published in Nature Communications, found Omicron immunity is low in pediatric patients with a prior COVID-19 or multisystem inflammatory syndrome (MIS-C) infection.

The study evaluated children’s ability to neutralize the Alpha, Beta, Gamma, Delta, and Omicron COVID-19 variants. The investigators collected serum and plasma samples from 3 independent pediatric disease cohorts: children younger than 5, children 5-11 years, and adolescents 12-21 years. None of the children and adolescents across the 3 cohorts were vaccinated against COVID-19.

The investigators performed antibody profiling on samples from a total of 177 children and adolescents who were hospitalized with acute COVID-19 or MIS-C, or outpatient mild convalescent COVID-19. Using pseudovirion neutralization assay (PsVNA), the investigators measured the antibody neutralization activity of the samples against the predominant SARS-CoV-2 WA1 strain and the 5 variants of concern. As a control, the investigators tested samples from 10 critically ill children positive for seasonal coronaviruses before 2019, and none of these controls demonstrated neutralization titers against COVID-19.

Children younger than 5 years old who were hospitalized with acute COVID-19 had significantly fewer intensive care unit (ICU) admissions than the MIS-C patients in this age range. This youngest cohort also required less respiratory support than adolescents 12-21 with the same acute illness. Among all MIS-C child and adolescent patients, there was no notable difference in disease severity by ICU admission, respiratory support, or mechanical ventilation.

SARS-CoV-2 WA1 nucleocapsid binding IgG were observed in all 177 children who had previously contracted COVID-19. In the children hospitalized with acute COVID-19, nucleocapsid binding IgG titer were stratified by age; the children younger than 5 had lower nucleocapsid IgG than the children 5 years and older.

The children demonstrated some loss of cross-neutralization against all COVID-19 variants, but this loss was most pronounced against Omicron. Less than 10% of pediatric patients had Omicron-neutralizing antibody titers; no children younger than 11 and only 2 of the adolescents demonstrated PsVNA50 titers above the seropositive cut-off against Omicron.

“We found that antibodies produced by prior infections in children don’t neutralize Omicron, meaning that unvaccinated children remain susceptible to Omicron,” said Adrienne Randolph, MD, MSc, a senior author of the study. “Omicron is very different from previous variants, with many mutations on the spike protein, and this work confirms that it is able to evade the antibody response.”

The investigators emphasized the importance of understanding the pediatric response to Omicron and subsequent developing COVID-19 variants. They said that vaccination induces a significantly more robust neutralizing antibody response to Omicron than “natural immunity” from a previous COVID-19 infection. Not only are unvaccinated children significantly more likely to develop severe or fatal COVID-19 disease, but they can transmit Omicron to other highly vulnerable populations.