# Evaluating Immunologic and Illness Outcomes of SARS-CoV-2 Infection in Vaccinated and Unvaccinated Children Aged ≥ 5 Years, in a Multisite Longitudinal Cohort

## TL;DR

Vaccinated children who later get infected with SARS-CoV-2 have stronger antibody responses and are less likely to have fevers than unvaccinated children.

## Contribution

This study provides new evidence on the immune and clinical outcomes of SARS-CoV-2 infection in vaccinated versus unvaccinated children.

## Key findings

- Vaccinated children had significantly higher antibody levels against SARS-CoV-2 Spike proteins compared to unvaccinated children.
- Vaccinated children were less likely to report fever during SARS-CoV-2 infection compared to unvaccinated children.

## Abstract

Children with prior vaccine-induced immunity at the time of infection had more robust antibody binding against the receptor-binding domain (RBD) and S2 domain of Spike, and experienced fever less often compared to unvaccinated children during primary SARS-CoV-2 infection.

Hybrid immunity, as a result of infection and vaccination to SARS-CoV-2, has been well studied in adults but limited evidence is available in children. We evaluated the antibody responses to primary SARS-CoV-2 infection among vaccinated and unvaccinated children aged ≥ 5 years. Methods: A longitudinal cohort study of children aged ≥ 5 was conducted during August 2021–August 2022, at sites in Arizona, Texas, Utah, and Florida. Children submitted weekly nasal swabs for PCR testing and provided sera 14–59 days after PCR-confirmed SARS-CoV-2 infection. Antibodies were measured by ELISA against the receptor-binding domain (RBD) and S2 domain of ancestral Spike (WA1), in addition to Omicron (BA.2) RBD, following infection in children, with and without prior monovalent ancestral mRNA COVID-19 vaccination. Results: Among the 257 participants aged 5 to 18 years, 166 (65%) had received at least two mRNA COVID-19 vaccine doses ≥ 14 days prior to infection. Of these, 53 occurred during Delta predominance, with 37 (70%) unvaccinated at the time of infection. The remaining 204 infections occurred during Omicron predominance, with 53 (26%) participants unvaccinated. After adjusting for weight, age, symptomatic infection, and gender, significantly higher mean RBD AUC values were observed among the vaccinated group compared to the unvaccinated group for both WA1 and Omicron (p < 0.0001). A smaller percentage of vaccinated children reported fever during illness, with 55 (33%) reporting fever compared to 44 (48%) unvaccinated children reporting fever (p = 0.021). Conclusions: Children with vaccine-induced immunity at the time of SARS-CoV-2 infection had higher antibody levels during convalescence and experienced less fever compared to unvaccinated children during infection.