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Association of Age With SARS-CoV-2 Antibody Response

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To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Are the quantity and quality of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) different among children, adolescents, and young adults?

Findings  In this cross-sectional study evaluating 31 426 SARS-CoV-2 antibody tests performed between April 9 and August 31, 2020, immunoglobin G levels were found to vary in different age groups, despite similar seroprevalence in the pediatric and adult patient populations. SARS-CoV-2 immunoglobin G and total antibody levels, neutralizing activity, and avidity exhibited negative correlations with age in patients aged 1 to 24 years.

Meaning  This analysis revealed distinct antibody responses in different age groups, suggesting that age-targeted strategies for disease screening and management as well as vaccine development may be warranted.


Importance  Accumulating evidence suggests that children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to manifest mild symptoms and are at a lower risk of developing severe respiratory disease compared with adults. It remains unknown how the immune response in children differs from that of adolescents and adults.

Objective  To investigate the association of age with the quantity and quality of SARS-CoV-2 antibody responses.

Design, Setting, and Participants  This cross-sectional study used 31 426 SARS-CoV-2 antibody test results from pediatric and adult patients. Data were collected from a New York City hospital from April 9 to August 31, 2020. The semiquantitative immunoglobin (Ig) G levels were compared between 85 pediatric and 3648 adult patients. Further analysis of SARS-CoV-2 antibody profiles was performed on sera from 126 patients aged 1 to 24 years.

Main Outcomes and Measures  SARS-CoV-2 antibody positivity rates and IgG levels were evaluated in patients from a wide range of age groups (1-102 years). SARS-CoV-2 IgG level, total antibody (TAb) level, surrogate neutralizing antibody (SNAb) activity, and antibody binding avidity were compared between children (aged 1-10 years), adolescents (aged 11-18 years), and young adults (aged 19-24 years).

Results  Among 31 426 antibody test results (19 797 [63.0%] female patients), with 1194 pediatric patients (mean [SD] age, 11.0 [5.3] years) and 30 232 adult patients (mean [SD] age, 49.2 [17.1] years), the seroprevalence in the pediatric (197 [16.5%; 95% CI, 14.4%-18.7%]) and adult (5630 [18.6%; 95% CI, 18.2%-19.1%]) patient populations was similar. The SARS-CoV-2 IgG level showed a negative correlation with age in the pediatric population (r = −0.45, P < .001) and a moderate but positive correlation with age in adults (r = 0.24, P < .001). Patients aged 19 to 30 years exhibited the lowest IgG levels (eg, aged 25-30 years vs 1-10 years: 99 [44-180] relative fluorescence units [RFU] vs 443 [188-851] RFU). In the subset cohort aged 1 to 24 years, IgG, TAb, SNAb and avidity were negatively correlated with age (eg, IgG: r = −0.51; P < .001). Children exhibited higher median (IQR) IgG levels, TAb levels, and SNAb activity compared with adolescents (eg, IgG levels: 473 [233-656] RFU vs 191 [82-349] RFU; P < .001) and young adults (eg, IgG levels: 473 [233-656] RFU vs 85 [38-150] RFU; P < .001). Adolescents also exhibited higher median (IQR) TAb levels, IgG levels, and SNAb activity than young adults (eg, TAb levels: 961 [290-2074] RFU vs 370 [125-697]; P = .006). In addition, children had higher antibody binding avidity compared with young adults, but the difference was not significant.

Conclusions and Relevance  The results of this study suggest that SARS-CoV-2 viral specific antibody response profiles are distinct in different age groups. Age-targeted strategies for disease screening and management as well as vaccine development may be warranted.

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Article Information

Accepted for Publication: February 10, 2021.

Published: March 22, 2021. doi:10.1001/jamanetworkopen.2021.4302

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Yang HS et al. JAMA Network Open.

Corresponding Author: Zhen Zhao, PhD, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 525 E 68th St, F-701, New York, NY 10065 (

Author Contributions: Drs Yang and Zhao had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Yang, Costa, and Racine-Brzostek contributed equally to this work.

Concept and design: Yang, Costa, Karbaschi, Zuk, Cushing, Zhao.

Acquisition, analysis, or interpretation of data: Yang, Costa, Racine-Brzostek, Acker, Yee, Chen, Karbaschi, Rand, Sukhu, Klasse, Chadburn, Zhao.

Drafting of the manuscript: Yang, Costa, Chen, Karbaschi, Rand, Zhao.

Critical revision of the manuscript for important intellectual content: Yang, Costa, Racine-Brzostek, Acker, Yee, Chen, Zuk, Sukhu, Klasse, Cushing, Chadburn, Zhao.

Statistical analysis: Yang, Yee, Chen, Klasse, Zhao.

Obtained funding: Klasse, Zhao.

Administrative, technical, or material support: Costa, Racine-Brzostek, Yee, Zuk, Rand, Sukhu, Zhao.

Supervision: Zuk, Cushing, Zhao.

Conflict of Interest Disclosures: Dr Zhao reported receiving nonfinancial support in the form of seed instruments and sponsored travel from ET Healthcare during the conduct of the study and receiving grants from Siemens and Polymedco and personal fees from Roche outside the submitted work. No other disclosures were reported.

Funding/Support: This research was partially funded by coronavirus disease 2019 research grants from Weill Cornell Medicine and Translational Research Program of the Department of Pathology and Laboratory Medicine Weill Cornell Medicine. Dr Klasse is funded by grants R01 AI110657 and R01 AI36082 from the National Institutes of Health.

Additional Contributions: We want to thank Heng Wu, MS, and Haode Chen, MS, from ET Healthcare for their technical assistance. They were compensated for their time.

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