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

Abstract

ABSTRACTBackgroundSARS-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.MethodsHumoral 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.ResultsThe 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.ConclusionLong-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.HIGHLIGHTSChildren 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-infectionIn contrast, T-cell responses to SARS-CoV-2 are globally reduced in children compared to adults but are alike to other seasonal β-coronaviruses.