SARS-CoV-2 antibody responses in children exhibit higher FcR engagement and avidity than in adults.

As intrinsic differences in humoral immune response to SARS-CoV-2 between children and adults remain unclear, we improved characterisation by defining the kinetics, specificity and function of antibodies to SARS-CoV-2 in children (n = 146, aged 9.4 ± 4.8 years with n = 257 samples) compared to adults (n = 85, aged 39.5 ± 15.2 years with n = 122 samples). We used plasma samples from an infection and vaccination-naive cohort study with RT-PCR confirmed ancestral B.1* SARS-CoV-2 virus infection with asymptomatic or mild disease, collected in Hong Kong between March to December 2020, from acute (0-14 days post infection) to convalescent (15-206 days) timepoints. Children had significantly lower primary antibody responses against SARS-CoV-2 proteins overall, leading to a less isotype switched response. While children had lower OC43 Spike and SARS-CoV-2 S2 IgG and avidity than adults, they exhibited higher avidities for SARS-CoV-2 whole Spike and Nucleocapsid, and higher levels of Spike FcγR-binding antibodies. Adults' SARS-CoV-2 antibody responses could be derived from high avidity pre-existing cross-reactive common cold coronavirus B cell responses, whilst children appear to generate a de novo SARS-CoV-2- specific Spike and Nucleocapsid IgG with robust Fc receptor (FcR) binding ability and high avidity at a higher proportion than adults, thus their responses are more targeted and functional for SARS-CoV-2.