RESUMEN
SARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody responses against spike and receptor binding domain (RBD) were high in children and seroconversion boosted antibody responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Seroneutralisation assays against alpha, beta and delta SARS-CoV-2 variants demonstrated comparable neutralising activity between children and adults. T cell responses against spike were >2-fold higher in children compared to adults and displayed a TH1 cytokine profile. SARS-CoV-2 spike-specific T cells were also detected in many seronegative children, revealing pre-existing responses that were cross-reactive with seasonal Alpha and Beta-coronaviruses. Importantly, all children retained high antibody titres and cellular responses at 6 months after infection whilst relative antibody waning was seen in adults. Spike-specific responses in children also remained broadly stable beyond 12 months. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection with focussed specificity against spike protein. These observations demonstrate novel features of SARS-CoV-2-specific immune responses in children and may provide insight into their relative clinical protection. Furthermore, this information will help to guide the introduction of vaccination regimens in the paediatric population.
RESUMEN
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MIS-C has overlapping clinical features with Kawasaki Disease (KD), a rare childhood vasculitis. MIS-C therapy is largely based on KD treatment protocols but whether these diseases share underpinning immunological perturbations is unknown. We performed deep immune profiling on blood samples from healthy children and patients with MIS-C or KD. Acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells; increased frequencies of B-cell plasmablasts and CD27-IgD-double-negative B-cells; and increased levels of pro-inflammatory (IL6, IL18, IP10, MCP1) but also anti-inflammatory (IL-10, IL1-RA, sTNFR1, sTNFR2) cytokines. Increased neutrophil count correlated with inflammation,cardiac dysfunction and disease severity. Two days after intravenous immunoglobulin (IVIG) treatment, MIS-C patients had increased CD163 expression on monocytes, expansion of a novel population of immature neutrophils, and decreased levels of pro- and anti-inflammatory cytokines in the blood accompanied by a transient increase in arginase in some patients. Our data show MIS-C and KD share substantial immunopathology and identify potential new mechanisms of action for IVIG, a widely used anti-inflammatory drug used to treat MIS-C, KD and other inflammatory diseases.
