Natural and hybrid immunity after SARS-CoV-2 infection in children and adolescents

Abstract Purpose The immune protection in children and adolescents with natural or hybrid immunity (vaccination & infection) against SARS-CoV-2 remains an understudied field. Aim of this study was to analyze different immune compartments in different age groups and whether humoral immune reactions correlate with a cellular immune response. Methods 72 children and adolescents with a preceding SARS-CoV-2 infection were recruited. 37 were vaccinated with an RNA-vaccine (BNT162b2). Humoral immunity was analyzed 3 to 26 months (median 10 months) after infection by measuring Spike protein (S), nucleocapsid (NCP) and neutralizing antibodies (nAB). Cellular immunity was analyzed using a SARS-CoV-2 specific interferon-γ release assay (IGRA). Results All children and adolescents had S antibodies; titers were higher in those with hybrid immunity (14900 BAU/ml vs. 2118 BAU/ml). NCP antibodies were detectable in > 90%. Neutralizing antibodies (nAB) were more frequently detected (90%) with higher titers (1914 RLU) in adolescents with hybrid immunity than in children with natural immunity (62,5%, 476 RLU). Children with natural immunity were less likely to have reactive IGRAs (43,8%) than adolescents with hybrid immunity (85%). The amount of interferon-γ released by T cells was comparable in natural and hybrid immunity. Conclusion Spike antibodies are the most reliable markers to monitor an immune reaction against SARS-CoV-2. High antibody titers of Spike antibodies and nAB correlated with cellular immunity, a phenomenon found only in adolescents with hybrid immunity. Hybrid immunity is associated with markedly higher antibody titers (S and nAB) and a higher probability of a cellular immune response than a natural immunity.