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Authors: Pierce, Carl A et al
Abstract: Children and youth infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have milder disease than do adults, and even among those with the recently described multisystem inflammatory syndrome, mortality is rare. The reasons for the differences in clinical manifestations are unknown but suggest that age-dependent factors may modulate the antiviral 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 coronavirus disease 2019 (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 interleukin-17A (IL-17A) and interferon-γ (IFN-γ), but not tumor necrosis factor-&#945; (TNF-&#945;) 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 patients with COVID-19. 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.
Journal: Sci. transl. med
Reviewer: Aris Floratos
Author-provided data: ?

paper: Pierce, C.A., Preston-Hurlburt, P., Dai, Y., Aschner, C.B., Cheshenko, N., Galen, B., Garforth, S., Herrera, N.G., Jangra, R., Morano, N.C., Orner, E., Sy, S., Chandran, K., Dziura, J., Almo, S., Ring, A., Keller, M., Herold, K., & Herold, B. (2020). Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Science Translational Medicine, 12.
contributor: Kevan Herold
contributor_organization: Yale University
contributor_email: kevan.herold@yale.edu

 

    • description: 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 serum concentration of IL-17A (Spearman r=-0.5, p<0.0001) and IFN-g (r=-0.44, p=0.0003), but not TNF or IL-6, were inversely related to age. Adults mounted a more robust T cellular response to the spike protein compared to pediatric patients as evidenced by increased expression of CD25+ on CD4+ T cells and frequency of IFN-g+CD4+ T cells. Moreover, the serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were significantly higher in adults compared to pediatric patients. The neutralizing titer correlated positively with age and negatively with IL-17A and IFN-g (p < 0.01). Together these findings demonstrate that the poor outcome in adults is not attributable to a failure to generate adaptive immune responses. They suggest that a more robust early immune response characterized by IL-17A and IFN-g that occurs in pediatric patients may prevent the excessive adaptive response associated with enhanced immunopathology.
    • exact_source: Table 1
    • tissue: PBMC and serum
    • immune_exposure: SARS-CoV-2
    • cohort: Children and adults
    • comparison: Severe vs mild disease
    • repository_id: N/A
    • platform: N/A
    • response_components: N/A
    • response_behavior: N/A