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Unique nasal cell states induced by common pediatric respiratory viruses

Jaclyn M L Walsh1,2,3,4, Lillian J Juttukonda1,4,5,6, Ying Tang1

  • 1Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.

Biorxiv : the Preprint Server for Biology
|May 4, 2026
PubMed

Insights

This study reveals how SARS-CoV-2, rhinovirus, and RSV uniquely alter the pediatric nasal lining at a cellular level. Understanding these virus-specific changes is crucial for addressing early childhood respiratory illnesses and asthma risk.

Area of Science:

  • Immunology
  • Virology
  • Pediatric Respiratory Medicine

Background:

  • Respiratory viral infections in young children cause significant illness and long-term airway problems.
  • The cellular-level impact of different viruses on the pediatric nasal mucosa is not well understood.

Purpose of the Study:

  • To create a detailed cellular atlas of the pediatric nasal mucosa during infections with SARS-CoV-2, rhinovirus, and respiratory syncytial virus (RSV).
  • To identify virus-specific cellular responses and immune programs associated with disease severity and asthma risk.

Main Methods:

  • Single-cell RNA sequencing was performed on 335,174 nasal epithelial and immune cells from 132 children under five with viral infections or uninfected.
  • Viral transcripts were mapped to individual cells to identify virus-specific infected epithelial states.
  • Analysis integrated asthma genome-wide association data to link cellular subsets to disease risk.

Main Results:

  • Distinct virus-specific infected epithelial cell states were identified for SARS-CoV-2 (NF-kB-responsive ciliated) and RSV (KRT17+ squamous-like).
  • Divergent mucosal responses included strong interferon (IFN) response in SARS-CoV-2, IL-13 secretory program in rhinovirus, and heightened inflammation in RSV.
  • RSV severity was linked to specific immune subsets and IFN signatures; rhinovirus-induced wheeze correlated with CST1+ goblet cell expansion.
  • A KRT13+ squamous epithelial subset was enriched for childhood-onset asthma risk loci.

Conclusions:

  • This single-cell atlas provides a comprehensive view of antiviral immunity in the pediatric nasal mucosa.
  • It defines virus-specific immune programs relevant to respiratory disease severity and early-life asthma risk.
  • The resource facilitates high-resolution annotation of independent pediatric cohorts globally.

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