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.
【저자키워드】 Innate immunity, Infectious disease, TMPRSS2, 【초록키워드】 COVID-19, coronavirus disease, viruses, SARS-CoV-2, IgG, Coronavirus disease 2019, coronavirus, Cytokines, Gene Expression, innate immune response, children, IP-10, oxygen, IFN signaling, angiotensin-converting enzyme 2, NLRP3 inflammasome, clinical outcomes, emergency department, respiratory viruses, Medicine, outcomes, Nasopharyngeal swab, Protein, Adults, Viral, nasopharyngeal swabs, IgA, clinical, RNA sequencing, IL-8, immune cells, epithelial cells, SARS Coronavirus, respiratory, SARS coronavirus 2, expression, quantitative reverse-transcription PCR, IFN-γ, Angiotensin-converting enzyme, IL-1β, cellular, Evidence, angiotensin, Pathways, severe disease, Other respiratory viruses, epithelial cell, evidence of, total protein, supplemental oxygen, Albert Einstein, both groups, enzyme, IFN-α2, disease manifestation, college, anti–SARS-CoV-2 IgG, nasal fluid, mucosal immune, robust, SARS-CoV-2 viral, PROTECT, not differ, died, required, contribute, expressed, other respiratory virus, NIH, quantified, expression of gene, Award, Eric, 【제목키워드】 COVID-19, children, mucosal, natural,