Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients

Abstract

Children and youth infected with SARS-CoV-2 have milder disease than do adults and, even among those with the recently described multi-system inflammatory syndrome (MIS-C), mortality is rare. The reasons for the differences in clinical manifestations are unknown, but suggest that age-dependent factors may modulate the anti-viral immune response. We compared cytokine, humoral, and cellular immune responses in pediatric (children and youth, age < 24 years) (n=65) and adult (n=60) patients with COVID-19 at a metropolitan hospital system in New York City. The pediatric patients had a shorter length of stay, decreased requirement for mechanical ventilation and lower mortality compared to adults. The serum concentrations of IL-17A and IFN-γ, but not TNF-α or IL-6, were inversely related to age. Adults mounted a more robust T cell response to the viral spike protein compared to pediatric patients as evidenced by increased expression of CD25+ on CD4+ T cells and the frequency of IFN-γ+CD4+ T cells. Moreover, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were higher in adults compared to pediatric COVID-19 patients. The neutralizing antibody titer correlated positively with age and negatively with IL-17A and IFN-γ serum concentrations. There were no differences in anti-spike protein antibody titers to other human coronaviruses. Together these findings demonstrate that the poor outcome in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses.