Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children

Area of Science:

• Immunology
• Virology
• Pediatrics

Background:

• Children experience lower rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 compared to adults.
• The molecular mechanisms behind this age-related protection remain largely unknown.

Purpose of the Study:

• To investigate the molecular and cellular differences in upper airway immune responses to SARS-CoV-2 between children and adults.
• To identify immune mechanisms contributing to children's protection against severe COVID-19.

Main Methods:

• Single-cell transcriptional landscape analysis of upper airway samples from SARS-CoV-2-negative and -positive children and adults.
• Comparison of immune cell populations and gene expression patterns across different age groups.

Main Results:

• Children show higher basal expression of pattern recognition receptors (e.g., MDA5, RIG-I) in airway cells, macrophages, and dendritic cells.
• Children exhibit distinct immune cell subpopulations, including KLRC1 (NKG2A)+ cytotoxic T cells and CD8+ T cells with a memory phenotype.
• These factors contribute to a more robust innate antiviral response in children upon SARS-CoV-2 infection.

Conclusions:

• Children's airway immune cells are primed for virus sensing, leading to a stronger early innate antiviral response.
• This enhanced immune response in children likely underlies their reduced susceptibility to severe COVID-19.