Systems serology detects functionally distinct coronavirus antibody features in children and elderly

Area of Science:

• Immunology
• Virology
• Public Health

Background:

• COVID-19 exhibits higher mortality in the elderly than in children.
• Understanding pre-existing immune responses to common human coronaviruses (hCoVs) is crucial for explaining these divergent clinical outcomes.
• Systems serology can analyze antibody profiles against SARS-CoV-2.

Purpose of the Study:

• To investigate baseline SARS-CoV-2 cross-reactive antibody responses in healthy children, adults, and the elderly before the pandemic.
• To compare immune responses between healthy individuals and COVID-19 patients.
• To understand age-dependent differences in humoral immunity relevant to SARS-CoV-2 infection.

Main Methods:

• Systems serology was employed to analyze coronavirus antibody responses.
• Antibody levels, Fcγ receptor binding, and antigen-specific IgA, IgG, and IgM were measured.
• Participants included pre-pandemic healthy children, adults, elderly individuals, and COVID-19 patients.

Main Results:

• Pre-pandemic healthy individuals had moderate, non-neutralizing SARS-CoV-2 cross-reactive antibodies.
• SARS-CoV-2 antigen-specific Fcγ receptor binding distinguished COVID-19 patients from healthy individuals.
• Healthy elderly showed higher cross-reactive SARS-CoV-2 IgA and IgG, while healthy children had elevated IgM.
• COVID-19 patients exhibited age-dependent differences in antibody class-switching and Fc responses.

Conclusions:

• Baseline humoral immunity to hCoVs varies significantly with age, influencing SARS-CoV-2 responses.
• Fcγ receptor binding is a key differentiator between infected and healthy individuals.
• Findings provide insights for developing COVID-19 vaccines, diagnostics, and therapeutics tailored to different age groups.