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Local and systemic responses to SARS-CoV-2 infection in children and adults

Masahiro Yoshida1,2, Kaylee B Worlock1, Ni Huang3

  • 1UCL Respiratory, Division of Medicine, University College London, London, UK.

Nature
|December 22, 2021
PubMed

Insights

Children experience milder COVID-19 due to robust innate interferon responses in their airways. This immune system difference restricts viral replication, explaining the less severe disease compared to adults.

Area of Science:

  • Immunology
  • Virology
  • Pediatrics

Background:

  • The reasons for typically milder coronavirus disease 2019 (COVID-19) in children remain unclear.
  • Understanding age-related differences in immune responses to SARS-CoV-2 is crucial.

Purpose of the Study:

  • To investigate the distinct immune responses to SARS-CoV-2 infection in paediatric versus adult patients.
  • To identify cellular and molecular mechanisms underlying the milder COVID-19 clinical course in children.

Main Methods:

  • Single-cell multi-omic profiling was performed on matched nasal, tracheal, bronchial, and blood samples from paediatric and adult COVID-19 patients and healthy controls (n=93).
  • Analysis focused on identifying differences in cellular states and immune signaling pathways between age groups.

Main Results:

  • Healthy children exhibit pre-activated interferon pathways in airway cells, further enhanced by SARS-CoV-2 infection, particularly in immune cells.
  • Adults showed increased cytotoxic T cells and interferon-stimulated populations, while children had elevated naive lymphocytes and depleted natural killer cells.
  • Dendritic cells were identified as initiators of early interferon signaling, and distinct epithelial cell states associated with COVID-19 and age were observed.

Conclusions:

  • Higher paediatric innate interferon responses in the airways appear to restrict viral replication and disease progression.
  • Differences in systemic immune cell populations and interferon signaling between children and adults contribute to the observed variations in COVID-19 severity.
  • The study elucidates key immunological mechanisms explaining why children generally experience milder COVID-19 outcomes.

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