The immunological basis for this condition is unclear but it is characterized by diffuse endothelial involvement and broad autoantibody production 10. MIS-C develops approximately 2–4 weeks after infection in children with a median age of 9 years 9. One unique feature of SARS-CoV-2 infection in children is the development of a rare complication known as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), also known as multisystem inflammatory syndrome in children (MIS-C), which shares features with Kawasaki disease and toxic shock syndrome 7, 8. Such studies are limited to date but have reported reduced magnitude of both antibody and cellular responses in comparison to adults and an absence of nucleocapsid-specific antibody responses during or early postinfection 3, 4, 5, 6. As such, there is interest in understanding the profile of the immune response to SARS-CoV-2 in children. SARS-CoV-2 infection in children is generally asymptomatic or mild and contrasts with high rates of hospitalization and death in older adults 2. The SARS-CoV-2 pandemic has resulted in over 4.2 million deaths so far and the most notable determinant of outcome is age at the time of primary infection 1. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. Spike-specific responses were also broadly stable beyond 12 months. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Neutralization of viral variants was comparable between children and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Here we compare antibody and cellular immunity in children (aged 3–11 years) and adults. SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Nature Immunology volume 23, pages 40–49 ( 2022) Cite this article Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection
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