SARS-CoV-2 accessory proteins reveal distinct serological signatures in children
Open accessAbstract
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.
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The ELISA assays as previously described were optimized and validated.
“The ELISA assays as previously described6,7 were optimized and validated.”
From Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population (2023) · cites this paper as [7]
The section ‘Different levels of antibodies to structural proteins in children and adults with SARS-CoV-2 infection’ (page unavailable) reports sensitivity and specificity for in-house ELISA assays, supporting an assessment of their diagnostic performance. The copy does not say those assays were optimized; its ELISA methods description instead specifies a commercial total-IgG kit used according to the manufacturer’s instructions. (LLM, conf=0.78)
Experimental — accuracy not yet measuredN- and ORF8-specific antibody responses were well maintained for at least 100 days postinfection.
“we previously reported that N- and ORF8-specific antibody responses were well maintained for at least 100 days postinfection7.”
From Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population (2023) · cites this paper as [7]
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Lau, J. J., Cheng, S. M. S., Leung, K., Lee, C. K., Hachim, A., Tsang, L. C. H., Yam, K. W. H., Chaothai, S., Kwan, K. K. H., Chai, Z. Y. H., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02219-5 · Cited by 198 · see citing works
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- Authors
- Hachim, A., Gu, H., Kavian, O., Mori, M., Kwan, M. Y. W., Chan, W. H., Yau, Y. S., Chiu, S. S., Tsang, O. T. Y., Hui, D. S. C., Mok, C. K. P., Ma, F. N. L., Lau, E. H. Y., Amarasinghe, G. K., Qavi, A. J., Cheng, S. M. S., Poon, L. L. M., Peiris, J. S. M., Valkenburg, S. A., & Kavian, N.
- Affiliations
- HKU-Pasteur Research Pole (HK)
- University of Hong Kong (HK)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Ishikawa Prefectural University (JP)
- Hospital Authority (HK)
- Chinese University of Hong Kong (HK)
- Washington University in St. Louis (US)
- The University of Melbourne (AU)
- Inserm (FR)
- Corresponding author
- Valkenburg, Sophie A.
- ORCID
- Venue
- Nature Communications
- Published
- 2022-05-26
- Volume
- 13
- Issue
- 1
- Pages
- 2951-2951
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9135746
- OpenAlex
- W4281559006
- Cited by
- 42
- References
- 7
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 15 · 2023: 16 · 2022: 8
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- HAL (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- Research Grants Council, University Grants Committee (T11-712/19-N)
- Food and Health Bureau of the Government of the Hong Kong Special Administrative Region | Health and Medical Research Fund (COVID-190126)
- Foundation for the National Institutes of Health (HHSN272201400006C)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, children, antibody response, accessory proteins, ORF8, ORF3a, ORF7a, ORF7b, Nsp1, spike protein, membrane proteins, E protein, asymptomatic infection, cytokines, interleukin-6, interleukin-8, MCP-1, sero-surveillance
- MeSH terms
- COVID-19, SARS-CoV-2, Adult, Antibody Specificity, Child, Humans, Immunoglobulin G, Cytokines
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