Abstract
SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3–11 years) 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. Neutralization of viral variants was comparable between children and 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. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. 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.
Highlights
SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear
We provide a comprehensive characterization of the convalescent humoral and cellular immune response in a cohort of 91 primary school-aged children compared with 154 adults taking part in the COVID-19 surveillance in school KIDs study[16]
A key finding was that the magnitude of the adaptive immune response to SARS-CoV-2 is higher in children compared to adults
Summary
SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. 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. One potential determinant of differential immune responses to SARS-CoV-2 across the life course may be the timing of exposure to the four additional endemic human coronaviruses (hCoVs) These comprise the Beta-coronaviruses OC43 and HKU-1, which have 38% and 35% amino acid homology with SARS-CoV-2, and the more distantly related Alpha-coronaviruses NL63 and 229E, each with around 31% homology[11]. Recurrent infections are common, generating concern that a similar pattern will be observed after SARS-CoV-2 infection
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