Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection

Area of Science:

• Immunology
• Virology
• Genomics

Background:

• Age is a critical determinant of severe outcomes from SARS-CoV-2 infection.
• Understanding age-related immune responses is crucial for managing COVID-19.
• Previous studies have not comprehensively analyzed transcriptomic differences across the lifespan.

Purpose of the Study:

• To investigate age-specific transcriptomic differences in immune responses to SARS-CoV-2 infection.
• To compare upper respiratory tract (URT) and peripheral blood immune profiles in children, adolescents, and adults.
• To identify how fever influences immune responses in SARS-CoV-2-infected individuals.

Main Methods:

• Transcriptomic analysis of URT and peripheral blood samples from 202 participants (1 week to 83 years).
• Included 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 65 healthy controls.
• Correlated transcriptomic data with clinical factors like age and fever.

Main Results:

• Younger individuals exhibit higher URT innate and adaptive immune gene expression.
• SARS-CoV-2 infection upregulates URT immune responses in children and adolescents.
• Adults show distinct peripheral blood responses involving myeloid, inflammatory, and coagulation pathways, unlike children's interferon-dominated responses.

Conclusions:

• SARS-CoV-2 immune responses exhibit distinct patterns across different age groups, from childhood to adulthood.
• Age-associated alterations in immune pathways contribute to varying COVID-19 severity.
• Fever impacts immune responses, causing blunted URT activity and heightened systemic activation.