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Updated: May 7, 2026
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Immune transcriptomic differences in paediatric patients with SARS-CoV-2 compared to other lower respiratory tract
Negusse Tadesse Kitaba1, Lesley Workman2, Cheryl Cohen3,4
1Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
Insights
This study reveals distinct gene expression patterns in children with severe SARS-CoV-2 infection, identifying key genes and pathways that differentiate disease severity and could inform new treatments.
Area of Science:
- Immunology
- Genomics
- Pediatrics
Background:
- Clinical severity of SARS-CoV-2 infection in children is variable.
- Understanding immunological responses is crucial for developing interventions.
Purpose of the Study:
- Compare whole blood transcriptomes in healthy children, those with mild/asymptomatic SARS-CoV-2, and severe SARS-CoV-2.
- Investigate transcriptomic differences in children with severe lower respiratory tract illness (LRTI) due to Respiratory Syncytial Virus (RSV-LRTI) or Pulmonary Tuberculosis (PTB).
Main Methods:
- Whole blood transcriptomic analysis of healthy children (N=127), mild/asymptomatic SARS-CoV-2 (N=71), severe SARS-CoV-2 (N=41), RSV-LRTI (N=47), and PTB (N=47).
- Differential gene expression analysis, pathway analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and cellular decomposition analysis.
Main Results:
- Identified >5000 differentially expressed genes, with specific genes highlighted for severe SARS-CoV-2, RSV-LRTI, and PTB.
- Pathway analysis revealed neutrophil degranulation and interferon gamma signaling enrichment in severe SARS-CoV-2.
- Identified gene modules shared between LRTI and distinct cell type depletions across severe conditions.
Conclusions:
- Discovered key genes (e.g., CBX7, TRAF1) for discriminating disease severity in SARS-CoV-2 infected children.
- Identified transcriptomic signatures for RSV-LRTI and PTB, offering potential therapeutic targets.
Abstract:
The clinical severity of SARS-CoV-2 infection in children varies, with asymptomatic or mild illness predominating and a minority developing severe disease. Understanding the immunological responses that underlie severity of disease may guide future development of preventive or therapeutic interventions. This study compared whole blood transcriptomes of healthy children (N=127), children with mild/asymptomatic SARS-CoV-2 infection (N=71) and children hospitalised with severe SARS-COV-2 (N=41), lower respiratory tract illness (LRTI) or LRTI due to Respiratory Syncytial Virus (RSV-LRTI) (N=47) or Pulmonary Tuberculosis (PTB) (N=47). We identified >5000 differentially expressed genes including: OLFM4, IFI27, CBX7, IGF2BP3, OTOF for severe SARS-CoV-2; IFI27, OTOF, SIGLEC1, IFI44L and USP18 for RSV-LRTI, and MMP8, LTF, IGF2BP3, GPR84, CD177, C1QC and DEFA4 for PTB, at false discovery rate (FDR) <0.05. Pathway analysis identified enrichment for neutrophil degranulation, interferon gamma signalling, overexpression of ribosomal proteins and depletion of immune response in severe SARS-CoV-2 compared to healthy (SAR-COV-2 uninfected) children. Weighted Gene Co-expression Network Analysis (WGCNA) identified 10 correlated gene modules shared between LRTI showing similar underlying response mechanisms. Cellular decomposition analysis identified the depletion of 22 cell types in severe SARS-CoV-2, 16 for RSV-LRTI and 21 for PTB compared to healthy SARS-CoV-2 uninfected control children. We identified 82 genes important for discriminating asymptomatic/mild from severe SARS-CoV-2 including CBX7, TRAF1, ZNF324 and CASS4; 93 healthy from severe SARS-CoV-2 including RORC, CBX7, NR3C2, MID2 and ADAMTS2; 110 genes for RSV-LRTI and 95 for PTB children which can be used for future therapeutic targets.
