TY - JOUR
T1 - Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients
AU - Pierce, Carl A.
AU - Preston-Hurlburt, Paula
AU - Dai, Yile
AU - Aschner, Clare Burn
AU - Cheshenko, Natalia V.
AU - Galen, Benjamin T.
AU - Garforth, Scott J.
AU - Herrera, Natalia G.
AU - Jangra, Rohit
AU - Morano, Nicholas C.
AU - Orner, Erika P.
AU - Sy, Sharlene
AU - Chandran, Kartik
AU - Dziura, James
AU - Almo, Steven C.
AU - Ring, Aaron
AU - Keller, Marla J.
AU - Herold, Kevan C.
AU - Herold, Betsy
N1 - Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved.
PY - 2020/10/7
Y1 - 2020/10/7
N2 - 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–α (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 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.
AB - 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–α (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 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.
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U2 - 10.1126/scitranslmed.abe8120
DO - 10.1126/scitranslmed.abe8120
M3 - Article
C2 - 32958614
AN - SCOPUS:85092749678
VL - 12
JO - Science Translational Medicine
JF - Science Translational Medicine
SN - 1946-6234
IS - 564
M1 - eabd5487
ER -