Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients
Authors: Aaron Ring
Steven C Almo
Natalia Cheshenko
Paula Preston-Hurlburt
Natalia G Herrera
Yile Dai
Sharlene Sy
Rohit K Jangra
Marla J Keller
Betsy C Herold
Kartik Chandran
James Dziura
Scott J Garforth
Erika Orner
Kevan C Herold
Benjamin Galen
Clare Burn Aschner
Carl A Pierce
Nicholas C Morano
Journal: Science Translational Medicine (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: children; youth; SARS-CoV-2; COVID-19; immune response
Affiliations: Department of Immunobiology, Yale University, New Haven, CT 06520., Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461., Department of Pediatrics, The Children’s Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY 10461., Department of Medicine, Montefiore Medical Center, Bronx, NY 10467., Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461., Department of Pathology, Montefiore Medical Center, Bronx, NY 10467., Department of Emergency Medicine and Biostatistics, Yale University, New Haven, CT 06520.

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 &lt;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. 

Retracted: No

PubPeer comments:
 Dr. Richard M. Fleming doesnu2019t appear to be cited or acknowledged in this paper, which could be surprising to readers of his claims at the link below. It is understandable that the authors are unaware of the u201cFleming Theoryu201d given [Flemingu2019s background] , but I wonder if the authors might comment on Dr. Flemingu2019s apparent claim to have independently developed a related theory, https: youtu.be tRtnLmkl68w u201cPremiered Sep 23, 2020 New research out of Albert Einstein, Yale and Montefiore confirm Fleming Theory and Treatment of enhanced InflammoThrombotic Response in patients who die with CoVid-19. [Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Sci Transl Med 2020. 10.1126 scitranslmed.abd5487] A dysfunctional immune response to CoVid-19 - as previously explained and shown in our submitted publications - explains poor outcomes in adults including being placed on a ventilator and dying!u201d ,