Differential Adaptive Immune Responses Following SARS-CoV-2 Infection in Children Compared to Adults

Background

SARS-CoV-2 infection elicits distinct clinical features in children and adults. Profiling the adaptive immune response following infection in children is essential to better understand and characterize these differences.

Methods

Humoral and cell-mediated immune responses from unvaccinated pediatric and adult participants were analyzed following asymptomatic or mild non-Omicron SARS-CoV-2 infection. Levels of IgG and IgA targeting spike (S), receptor-binding domain (RBD), and nucleocapsid (N) proteins of SARS-CoV-2 were measured, while neutralizing antibody (nAb) titers were assessed against three viral strains (Wuhan, Omicron BA.1 and BA.4/BA.5). Specific T-cell memory responses were investigated by quantifying interferon-gamma (IFN-γ) secreting cells after stimulation with ancestral and variant strains of SARS-CoV-2, and seasonal human β- coronaviruses (HCoV)-OC43 and -HKU1.

Results

The study comprised 28 children (3 to 17 [median=10] years old) and 28 adults (19 to 62 [median=42]). At a mean time of seven months (± 2.8 months) after SARS-CoV-2 infection, children and adults mounted comparable antibody levels against S and RBD, as well as similar neutralization capacity. However, children displayed a weaker cellular memory response to SARS- CoV-2 than adults, with a median of 88 [28-184] spot forming units per million of PBMCs in children compared to 208 [141-340] in adults (***, P < .001). In children, the level of IFN-γ secreting cells in response to SARS-CoV-2 corresponds to that of seasonal coronaviruses.

Conclusion

Long-term memory T-cell responses to SARS-CoV-2 are enhanced in adults compared to children who demonstrate equivalent responses to SARS-CoV-2 and other HCoV.

HIGHLIGHTS

• Children infected with SARS-CoV-2 show comparable binding and neutralizing antibody levels as adults seven months after infection.

• There are notable differences in the intensity of the T-cell response following SARS-CoV- 2 infection between children and adults.

• Children have more pronounced T-cell immunodominance towards the spike versus non- spike proteins compared to adults at seven months post-infection

• In contrast, T-cell responses to SARS-CoV-2 are globally reduced in children compared to adults but are alike to other seasonal β-coronaviruses.