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Natural mucosal barriers and COVID-19 in children
Carl A. Pierce, … , Kevan C. Herold, Betsy C. Herold
Carl A. Pierce, … , Kevan C. Herold, Betsy C. Herold
Published April 6, 2021
Citation Information: JCI Insight. 2021;6(9):e148694. https://doi.org/10.1172/jci.insight.148694.
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Clinical Medicine Infectious disease

Natural mucosal barriers and COVID-19 in children

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Abstract

BACKGROUND Coronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS coronavirus 2 (SARS-CoV-2) protects against severe disease.METHODS Clinical outcomes, SARS-CoV-2 viral copies, and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the emergency department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse-transcription PCR. Total protein, cytokines, and anti–SARS-CoV-2 IgG and IgA were quantified in nasal fluid.RESULTS SARS-CoV-2 copies, angiotensin-converting enzyme 2, and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with IFN signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1β protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells, whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti–SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen, whereas 7 adults did (P = 0.03); 4 adults died.CONCLUSION These findings provide direct evidence of a more vigorous early mucosal immune response in children compared with adults and suggest that this contributes to favorable clinical outcomes.FUNDING NIH grants R01 AI134367, UL1 TR002556, T32 AI007501, T32GM007288, P30 AI124414; an Albert Einstein College of Medicine Dean’s COVID-19 Pilot Research Award; and the Eric J. Heyer, MD, PhD Translational Research Pilot Project Award.

Authors

Carl A. Pierce, Sharlene Sy, Benjamin Galen, Doctor Y. Goldstein, Erika Orner, Marla J. Keller, Kevan C. Herold, Betsy C. Herold

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Figure 1

Transcriptional profiles in pediatric and adult nasopharyngeal samples.

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Transcriptional profiles in pediatric and adult nasopharyngeal samples.
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(A) Ct values and days of symptoms prior to presentation in 27 adult and 11 pediatric patients, and ACE2 read counts in cells isolated from NP swabs obtained at presentation in 15 adult and 6 pediatric samples. Bars show mean ± 95% CI. (B) The expression of ACE2 and TMPRSS2 from the RNA-Seq studies. (C) Volcano plot of the expression of genes analyzed by RNA-Seq more strongly in pediatric (right) and adult (left) patients. (D) Principal component plot of RNA-Seq data; n = 15 adult and 6 pediatric samples. Ovals are 95% confidence ellipses. (E) Heatmap showing expression of the top 50 contributing genes in principal components 1, 2, and 3.

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