Nasal mucosal IgA levels against SARS-CoV-2 and seasonal coronaviruses are low in children but boosted by reinfection

Repeated coronavirus infections in childhood drive progressive maturation of systemic immune responses into adulthood. Analyses of immune responses in children have focused primarily upon systemic assessment but the importance of mucosal immunity is increasingly recognised. We studied virus-specific antibody responses in contemporaneous nasal swab and blood samples from 99 children (4-15 years) and 28 adults (22-56 years), all of whom had prior SARS-CoV-2 infection. Whilst mucosal IgA titres against Influenza and Respiratory Syncytial virus were comparable between children and adults, those against all coronaviruses, including SARS-CoV-2, were lower in children. Mucosal IgA antibodies demonstrated comparable relative neutralisation capacity in both groups and retained activity against recent omicron variants such as XBB.1 which are highly evasive of IgG neutralisation. SARS-CoV-2 reinfection preferentially enhanced mucosal IgA responses whilst the impact of vaccination was more modest. Nasal IgA levels against coronaviruses thus display a pattern of incremental response to reinfection which likely determines the natural history of reinfection. This highlights the particular significance of developing mucosal vaccines against coronaviruses in children.