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Long-term Immune Response to SARS-CoV-2 Infection Among Children and Adults After Mild Infection

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Key Points

Question  What are the long-term features of the immune response to SARS-CoV-2 in children compared with adults?

Findings  In this cohort study of 252 family clusters with COVID-19, anti–SARS-CoV-2 spike receptor-binding domain IgG persisted until 12 months after infection in all age groups, showing significant higher antibody peaks for younger individuals at every follow-up time point. Children younger than 3 years were found to develop higher levels of binding antibodies compared with adults older than 18 years.

Meaning  This study provided novel insights into the long-term features of the immune response to COVID-19 for different age classes, which could help in optimizing future COVID-19 vaccination strategies and prevention policies.

Abstract

Importance  Understanding the long-term immune response against SARS-CoV-2 infection in children is crucial to optimize vaccination strategies. Although it is known that SARS-CoV-2 antibodies may persist in adults 12 months after infection, data are limited in the pediatric population.

Objective  To examine long-term anti–SARS-CoV-2 spike receptor-binding domain (S-RBD) IgG kinetics in children after SARS-CoV-2 infection.

Design, Setting, and Participants  In this single-center, prospective cohort study, patients were enrolled consecutively from April 1, 2020, to August 31, 2021, at the COVID-19 Family Cluster Follow-up Clinic, Department of Women's and Children's Health, University Hospital of Padua. A cohort of 252 COVID-19 family clusters underwent serologic follow-up at 1 to 4, 5 to 10, and more than 10 months after infection with quantification of anti–S-RBD IgG by chemiluminescent immunoassay.

Exposures  SARS-CoV-2 infection.

Results  Among 902 study participants, 697 had confirmed SARS-CoV-2 infection, including 351 children or older siblings (mean [SD] age, 8.6 [5.1] years) and 346 parents (mean [SD] age, 42.5 [7.1] years). Among 697 cases, 674 (96.7%) were asymptomatic or mild. Children had significantly higher S-RBD IgG titers than older patients across all follow-up time points, with an overall median S-RBD IgG titer in patients younger than 3 years 5-fold higher than adults (304.8 [IQR, 139.0-516.6] kBAU/L vs 55.6 [24.2-136.0] kBAU/L, P < .001). Longitudinal analysis of 56 study participants sampled at least twice during follow-up demonstrated the persistence of antibodies up to 10 months from infection in all age classes, despite a progressive decline over time.

Conclusions and Relevance  In this cohort study of Italian children and adults following SARS-CoV-2 infection different kinetics of SARS-CoV-2 antibodies were found across several age classes of individuals with asymptomatic or mild COVID-19, which could help in optimizing COVID-19 vaccination strategies and prevention policies. This work provides further evidence of sustained immune response in children up to 1 year after primary SARS-CoV-2 infection.

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Article Information

Accepted for Publication: May 17, 2022.

Published: July 13, 2022. doi:10.1001/jamanetworkopen.2022.21616

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Di Chiara C et al. JAMA Network Open.

Corresponding Author: Costanza Di Chiara, MD, Division of Pediatric Infectious Diseases, Department for Women’s and Children’s Health, University of Padua, Via Giustiniani 3, Padua, Italy (costanza.dichiara@phd.unipd.it).

Author Contributions: Drs Giaquinto and Di Chiara had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Padoan and Prof Giaquinto contributed as co–last authors.

Concept and design: Di Chiara, Cantarutti, Costenaro, Donà, Palma, Di Salvo, De Rossi, Giaquinto.

Acquisition, analysis, or interpretation of data: Di Chiara, Cantarutti, Costenaro, Bonfante, Cosma, Ferrarese, Cozzani, Petrara, Carmona, Liberati, Palma, Plebani, Padoan.

Drafting of the manuscript: Di Chiara, Cantarutti, Costenaro, Cosma, Ferrarese, Liberati, Padoan.

Critical revision of the manuscript for important intellectual content: Cantarutti, Costenaro, Donà, Bonfante, Cozzani, Petrara, Carmona, Palma, Di Salvo, De Rossi, Plebani, Padoan, Giaquinto.

Statistical analysis: Cantarutti, Costenaro, Padoan.

Obtained funding: Palma, Giaquinto.

Administrative, technical, or material support: Di Chiara, Bonfante, Cosma, Cozzani, Petrara, Carmona, Liberati, Palma.

Supervision: Costenaro, Donà, Palma, Di Salvo, De Rossi, Plebani, Padoan, Giaquinto.

Conflict of Interest Disclosures: Dr Palma reported receiving grants from the Chiesi Foundation to support research about immunologic aspects of long-term COVID-19 in children outside the submitted work. No other disclosures were reported.

Funding/Support: This work was partially supported by ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic). ORCHESTRA has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement 101016167.

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The submission for publication was discussed with the funder.

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