Comparative analysis of adaptive immunity to SARS-CoV-2 in infected children and adults

SARS-CoV-2 infection in children is most often mild and resembles that of seasonal coronaviruses. Profiling the adaptive immune response following infection may help to inform on the protective mechanisms mediating immunity in children and adults.

Humoral and cell-mediated immune responses from unvaccinated pediatric and adult participants were analyzed following non-Omicron SARS-CoV-2 infection. 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.

Twenty-eight children (3-17 [median = 10] years) and 28 adults (19-62 [median = 42] years) were sampled at a mean time of 7 months (±2.8 months) after SARS-CoV-2 infection. Antibody levels against spike (S) and the receptor-binding domain (RBD), as well as neutralization capacity, were equivalent in adults and children. However, children displayed a lower number of IFN-γ secreting T cells in response to SARS-CoV-2 compared to adults, with a median of 88 [28-184] spot-forming units (SFU) per million of cells in children compared to 208 [141-340] in adults (P < 0.001). In children, the IFN-γ⁺ responses to SARS-CoV-2 were of similar magnitude as the responses to seasonal β-coronaviruses (P > 0.05). In contrast, adults exhibited heightened T cell responses to SARS-CoV-2 than they did to HCoV-OC43 (median of 80 [45-135] SFU/10⁶ cells, P < 0.0001) and HCoV-HKU1 (median of 98 [59-151] SFU/10⁶ cells, P < 0.01).

In children, the functional T cell memory responses to SARS-CoV-2, assessed through IFN-γ secretion in response to peptide stimulation, are comparable to those of HCoVs and lower compared to adults.

While binding and neutralizing antibody levels to SARS-CoV-2 are largely comparable in children and adults, the strength of memory T cell responses induced by infection is reduced in children compared to adults. Adults present heightened cellular memory responses to SARS-CoV-2, but not to seasonal β-coronaviruses HCoV-OC43 and HCoV-HKU1. In contrast, children's T cell memory responses to SARS-CoV-2 closely mirror their response to common seasonal β-coronaviruses.