SARS-CoV-2 accessory proteins reveal distinct serological signatures in children

• Published in: Nature communications Vol. 13; no. 1; pp. 2951 - 14
• Main Authors: Hachim, Asmaa, Gu, Haogao, Kavian, Otared, Mori, Masashi, Kwan, Mike Y. W., Chan, Wai Hung, Yau, Yat Sun, Chiu, Susan S., Tsang, Owen T. Y., Hui, David S. C., Mok, Chris K. P., Ma, Fionn N. L., Lau, Eric H. Y., Amarasinghe, Gaya K., Qavi, Abraham J., Cheng, Samuel M. S., Poon, Leo L. M., Peiris, J. S. Malik, Valkenburg, Sophie A., Kavian, Niloufar
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 13/21; 631/250/2152; 631/250/255; 82/80; Adult; Adults; Antibodies; Antibody response; Antibody Specificity; Antigens; Asymptomatic; Child; Children; COVID-19; Cytokines; Humanities and Social Sciences; Humans; Immunoglobulin G; Infections; Interleukin 6; Interleukin 8; Life Sciences; Monocyte chemoattractant protein 1; Morbidity; multidisciplinary; Pediatrics; Priming; Principal components analysis; Proteins; SARS-CoV-2; Science; Science (multidisciplinary); Serology; Severe acute respiratory syndrome coronavirus 2; Signatures; Structural proteins; Sars-cov-2; Antibodies
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30699-5

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. The antibody response of children to SARS-CoV-2 is less well studied than in adults. Here Hachim et al. show that children have reduced antibody levels to structural proteins and suggest that the predominance of antibody responses to non-structural proteins can be used to discriminate infection and vaccination.