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Association of SARS-CoV-2 Seropositivity and Symptomatic Reinfection in Children in Nicaragua

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Key Points

Question  What is the burden of COVID-19 among young children, and how does risk of reinfection vary with age?

Findings  In this cohort study of 1964 children in Nicaragua aged 0 to 14 years, children younger than 2 years had the highest rates of symptomatic and severe COVID-19, particularly compared with children aged 5 to 14 years.

Meaning  These findings suggest that the burden of COVID-19 and associated severe illness may not be evenly distributed across age groups in children.

Abstract

Importance  The impact of the SARS-CoV-2 pandemic on children remains unclear. Better understanding of the burden of COVID-19 among children and their risk of reinfection is crucial, as they will be among the last groups vaccinated.

Objective  To characterize the burden of COVID-19 and assess how risk of symptomatic reinfection may vary by age among children.

Design, Setting, and Participants  In this prospective, community-based pediatric cohort study conducted from March 1, 2020, to October 15, 2021, 1964 nonimmunocompromised children aged 0 to 14 years were enrolled by random selection from the Nicaraguan Pediatric Influenza Cohort, a community-based cohort in District 2 of Managua, Nicaragua. Additional newborn infants aged 4 weeks or younger were randomly selected and enrolled monthly via home visits.

Exposures  Prior COVID-19 infection as confirmed by positive anti–SARS-CoV-2 antibodies (receptor binding domain and spike protein) or real-time reverse transcriptase–polymerase chain reaction (RT-PCR)–confirmed COVID-19 infection at least 60 days before current COVID-19 infection.

Main Outcomes and Measures  Symptomatic COVID-19 cases confirmed by real-time RT-PCR and hospitalization within 28 days of symptom onset of a confirmed COVID-19 case.

Results  This cohort study assessed 1964 children (mean [SD] age, 6.9 [4.4] years; 985 [50.2%] male). Of 1824 children who were tested, 908 (49.8%; 95% CI, 47.5%-52.1%) were seropositive during the study. There were also 207 PCR-confirmed COVID-19 cases, 12 (5.8%) of which were severe enough to require hospitalization. Incidence of COVID-19 was highest among children younger than 2 years (16.1 cases per 100 person-years; 95% CI, 12.5-20.5 cases per 100 person-years), which was approximately 3 times the incidence rate in any other child age group assessed. In addition, 41 symptomatic SARS-CoV-2 episodes (19.8%; 95% CI, 14.4%-25.2%) were reinfections.

Conclusions and Relevance  In this prospective, community-based pediatric cohort study, rates of symptomatic and severe COVID-19 were highest among the youngest participants, with rates stabilizing at approximately 5 years of age. In addition, symptomatic reinfections represented a large proportion of symptomatic COVID-19 cases.

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Article Information

Accepted for Publication: April 21, 2022.

Published: June 27, 2022. doi:10.1001/jamanetworkopen.2022.18794

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

Corresponding Author: Aubree Gordon, PhD, Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (gordonal@umich.edu).

Author Contributions: Drs Kubale and Gordon 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. Drs Kubale and Balmaseda contributed equally to this work.

Concept and design: Kubale, Harris, Kuan, Gordon.

Acquisition, analysis, or interpretation of data: Kubale, Balmaseda, Frutos, Sanchez, Plazaola, Ojeda, Saborio, Lopez, Barilla, Vasquez, Moreira, Gajewski, Campredon, Maier, Chowdhury, Cerpas, Gordon.

Drafting of the manuscript: Kubale, Kuan, Gordon.

Critical revision of the manuscript for important intellectual content: Kubale, Balmaseda, Frutos, Sanchez, Plazaola, Ojeda, Saborio, Lopez, Barilla, Vasquez, Moreira, Gajewski, Campredon, Maier, Chowdhury, Cerpas, Harris, Gordon.

Statistical analysis: Kubale, Frutos.

Obtained funding: Gordon.

Administrative, technical, or material support: Kubale, Balmaseda, Sanchez, Plazaola, Ojeda, Saborio, Lopez, Barilla, Vasquez, Moreira, Gajewski, Campredon, Maier, Chowdhury, Cerpas, Harris, Kuan, Gordon.

Supervision: Balmaseda, Sanchez, Plazaola, Ojeda, Lopez, Barilla, Vasquez, Cerpas, Gordon.

Conflict of Interest Disclosures: Dr Gordon reported serving on a respiratory syncytial virus vaccine scientific advisory board for Janssen Pharmaceuticals and a COVID-19 scientific advisory board for Gilead Sciences outside the submitted work. No other disclosures were reported.

Funding/Support: The design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation of the manuscript were supported by grant U01 AI144616 and contract HHSN272201400006C from the National Institute for Allergy and Infectious Diseases at the National Institutes of Health and a grant from Open Philanthropy (Dr Gordon).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Leo Poon, MPhil, DPhil (HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China, and Division of Public Health Laboratory Sciences, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China), provided the protocol and controls for reverse transcriptase–polymerase chain reaction testing. Florian Krammer, PhD (Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, and Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York), shared the receptor-binding domain and Spike constructs and provided technical advice. Janet Smith, PhD, Melanie Ohi, PhD, and their groups at the Center of Structural Biology at the University of Michigan Life Sciences Institute produced the proteins and antibodies for the enzyme-linked immunosorbent assays. We thank the study participants and their families, the amazing study staff, and the people of Nicaragua, without whom none of this would be possible.

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