Related Experiment Video
Updated: Sep 22, 2025
Author Spotlight: Advancing Antiviral Strategies Through Novel Immunocapture and Mass Spectrometry Techniques
Published on: January 12, 2024
SARS-CoV-2 accessory proteins reveal distinct serological signatures in children
Asmaa Hachim1, Haogao Gu2, Otared Kavian3
1HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Insights
Children infected with SARS-CoV-2 show distinct antibody responses compared to adults. Specific antibodies targeting ORF3d and ORF8 can accurately identify infection in children, offering a potential serological tool.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Antibody response in COVID-19 influences clinical severity, diagnosis, and long-term protection.
- Children generally experience lower morbidity from SARS-CoV-2 infection compared to adults.
- Understanding pediatric antibody kinetics is crucial for assessing infection and immunity.
Purpose of the Study:
- To compare the antibody response magnitude and kinetics between infected children and adults.
- To identify specific SARS-CoV-2 antigens that can discriminate infection in pediatric populations.
- To investigate the correlation between cytokine profiles and antibody responses in children.
Main Methods:
- Serum samples from 122 children and 71 adults with confirmed SARS-CoV-2 infection were analyzed.
- Luciferase Immuno-Precipitation System (LIPS) assay was used to measure IgG antibodies against a 14-antigen panel.
- Circulating cytokines were quantified, and principal component analysis was applied to identify serological signatures.
Main Results:
- Infected children exhibited lower levels of antibodies to Spike, Membrane, ORF3a, ORF7a, and ORF7b proteins compared to adults.
- Children showed comparable ORF8 and elevated E-specific antibodies relative to adults.
- A combination of ORF3d and ORF8 antibodies accurately differentiated SARS-CoV-2 infection in children; distinct pediatric serological signatures were identified.
Conclusions:
- Distinct antibody profiles exist between pediatric and adult SARS-CoV-2 infections.
- Antibodies targeting ORF3d and ORF8 serve as effective biomarkers for identifying pediatric COVID-19 cases.
- Antibodies to internal SARS-CoV-2 proteins may be valuable for serosurveillance in vaccinated children.
Abstract:
The antibody response magnitude and kinetics may impact clinical severity, serological diagnosis and long-term protection of COVID-19, which may play a role in why children experience lower morbidity. We therefore tested samples from 122 children in Hong Kong with symptomatic (n = 78) and asymptomatic (n = 44) SARS-CoV-2 infections up to 200 days post infection, relative to 71 infected adults (symptomatic n = 61, and asymptomatic n = 10), and negative controls (n = 48). We assessed serum IgG antibodies to a 14-wide antigen panel of structural and accessory proteins by Luciferase Immuno-Precipitation System (LIPS) assay and circulating cytokines. Infected children have lower levels of Spike, Membrane, ORF3a, ORF7a, ORF7b antibodies, comparable ORF8 and elevated E-specific antibodies than adults. Combination of two unique antibody targets, ORF3d and ORF8, can accurately discriminate SARS-CoV-2 infection in children. Principal component analysis reveals distinct pediatric serological signatures, and the highest contribution to variance from adults are antibody responses to non-structural proteins ORF3d, NSP1, ORF3a and ORF8. From a diverse panel of cytokines that can modulate immune priming and relative inflammation, IL-8, MCP-1 and IL-6 correlate with the magnitude of pediatric antibody specificity and severity. Antibodies to SARS-CoV-2 internal proteins may become an important sero surveillance tool of infection with the roll-out of vaccines in the pediatric population.
