Tracking the clonal dynamics of SARS-CoV-2-specific T cells in children and adults with mild/asymptomatic COVID-19

Area of Science:

• Immunology
• Virology
• Pediatrics

Background:

• Children infected with SARS-CoV-2 generally experience milder COVID-19 than adults.
• Understanding age-specific immune responses to SARS-CoV-2 is crucial for infection-induced immunity.
• Mechanisms behind these age differences are under investigation.

Purpose of the Study:

• To investigate the differences in T cell responses to SARS-CoV-2 infection between children and adults.
• To explore the long-term implications of these immune differences on cellular immunity and reinfection resistance.

Main Methods:

• Longitudinal multimodal analysis of T cell compartments in children and adults with COVID-19.
• Assessment of T cell interferon activation, cytotoxicity, and exhaustion.
• Characterization of SARS-CoV-2-specific T cell populations (naïve vs. memory).

Main Results:

• Children with mild/asymptomatic COVID-19 showed a smaller T cell footprint compared to adults.
• Adults exhibited greater systemic T cell interferon activation, cytotoxicity, and exhaustion.
• Children had diverse naïve T cells, while adults had expanded memory T cells specific to SARS-CoV-2.
• A novel population of interferon-activated naïve T cells expanded in adults during convalescence but not in children.
• Robust CD4+ T cell memory responses developed in adults, but not in children.

Conclusions:

• Rapid SARS-CoV-2 clearance in children may compromise their cellular immunity.
• Age-specific differences in T cell responses impact the development of robust immunological memory.
• Children's immune profiles suggest a potential compromise in their ability to resist reinfection.