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Assessment of Clinical and Virological Characteristics of SARS-CoV-2 Infection Among Children Aged 0 to 4 Years and Their Household Members

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

Question  Do community-acquired SARS-CoV-2 infections differ in adults and children aged 0 to 4 years with respect to incidence, symptoms, and detected viral load?

Findings  In this cohort study of 690 participants from 175 households in Maryland conducted from November 2020 to October 2021, 54 incident SARS-CoV-2 infections were detected in 8.6% of children aged 0 to 4 years, 11.0% of children aged 5 to 17 years, and 6.3% of adults. Children were more frequently asymptomatic or mildly symptomatic than adults; highest detected viral loads correlated with the number of symptoms in adults but not in young children.

Meaning  This study’s findings suggest that symptomatic screening for SARS-CoV-2 infection may be insufficient to control outbreaks in settings in which young children congregate.


Importance  Few studies have prospectively assessed SARS-CoV-2 community infection in children aged 0 to 4 years. Information about SARS-CoV-2 incidence and clinical and virological features in young children could help guide prevention and mitigation strategies.

Objective  To assess SARS-CoV-2 incidence, clinical and virological features, and symptoms in a prospective household cohort and to compare viral load by age group, symptoms, and SARS-CoV-2 lineage in young children, older children, and adults.

Design, Setting, and Participants  This prospective cohort study enrolled 690 participants from 175 Maryland households with 1 or more children aged 0 to 4 years between November 24, 2020, and October 15, 2021. For 8 months after enrollment, participants completed weekly symptom questionnaires and submitted self-collected nasal swabs for SARS-CoV-2 qualitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing, quantitative RT-PCR testing, and viral lineage determination. For the analyses, SARS-CoV-2 Alpha and Delta lineages were considered variants of interest or concern. Sera collected at enrollment and at approximately 4 months and 8 months after enrollment were assayed for SARS-CoV-2 spike and nucleocapsid protein antibodies.

Main Outcomes and Measures  Incidence, clinical and virological characteristics, and symptoms of SARS-CoV-2 infection by age group and correlations between (1) highest detected viral load and symptom frequency and (2) highest detected viral load and SARS-CoV-2 lineage.

Results  Among 690 participants (355 [51.4%] female and 335 [48.6%] male), 256 individuals (37.1%) were children aged 0 to 4 years, 100 (14.5%) were children aged 5 to 17 years, and 334 (48.4%) were adults aged 18 to 74 years. A total of 15 participants (2.2%) were Asian, 24 (3.5%) were Black, 603 (87.4%) were White, 43 (6.2%) were multiracial, and 5 (0.7%) were of other races; 33 participants (4.8%) were Hispanic, and 657 (95.2%) were non-Hispanic. Overall, 54 participants (7.8%) had SARS-CoV-2 infection during the surveillance period, including 22 of 256 children (8.6%) aged 0 to 4 years, 11 of 100 children (11.0%) aged 5 to 17 years, and 21 of 334 adults (6.3%). Incidence rates per 1000 person-weeks were 2.25 (95% CI, 1.28-3.65) infections among children aged 0 to 4 years, 3.48 (95% CI, 1.59-6.61) infections among children aged 5 to 17 years, and 1.08 (95% CI, 0.52-1.98) infections among adults. Children aged 0 to 17 years with SARS-CoV-2 infection were more frequently asymptomatic (11 of 30 individuals [36.7%]) compared with adults (3 of 21 individuals [14.3%]), with children aged 0 to 4 years most frequently asymptomatic (7 of 19 individuals [36.8%]). The highest detected viral load did not differ between asymptomatic vs symptomatic individuals overall (median [IQR], 2.8 [1.5-3.3] log10 copies/mL vs 2.8 [1.8-4.4] log10 copies/mL) or by age group (median [IQR] for ages 0-4 years, 2.7 [2.4-4.4] log10 copies/mL; ages 5-17 years: 2.4 [1.1-4.0] log10 copies/mL; ages 18-74 years: 2.9 [1.9-4.6] log10 copies/mL). The number of symptoms was significantly correlated with viral load among adults (R = 0.69; P < .001) but not children (ages 0-4 years: R = 0.02; P = .91; ages 5-17 years: R = 0.18; P = .58). The highest detected viral load was greater among those with Delta variant infections (median [IQR], 4.4 [3.9-5.1] log10 copies/mL) than those with infections from variants not of interest or concern (median [IQR], 1.9 [1.1-3.6] log10 copies/mL; P = .009) or those with Alpha variant infections (median [IQR], 2.6 [2.3-3.4] log10 copies/mL; P = .006).

Conclusions and Relevance  In this study, SARS-CoV-2 infections were frequently asymptomatic among children aged 0 to 4 years; the presence and number of symptoms did not correlate with viral load. These findings suggest that symptom screening may be insufficient to prevent outbreaks involving young children.

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Article Information

Accepted for Publication: June 10, 2022.

Published: August 31, 2022. doi:10.1001/jamanetworkopen.2022.27348

Correction: This article was corrected on September 15, 2022, to correct a sentence in the Discussion.

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

Corresponding Author: Ruth A. Karron, MD, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, 624 N Broadway, Baltimore, MD 21205 (rkarron@jhu.edu).

Author Contributions: Dr Karron and Ms Hetrich 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.

Concept and design: Karron, Knoll, Meece, Dawood.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Karron, Na, Schappell, Lee.

Critical revision of the manuscript for important intellectual content: Karron, Hetrich, Knoll, Meece, Hanson, Tong, Lee, Veguilla, Dawood.

Statistical analysis: Hetrich, Na, Knoll.

Obtained funding: Meece.

Administrative, technical, or material support: Schappell, Meece, Tong, Lee, Veguilla, Dawood.

Supervision: Karron, Knoll, Meece, Dawood.

Conflict of Interest Disclosures: Dr Karron reported receiving grants from the Centers for Disease Control and Prevention (CDC) during the conduct of the study. Ms Hetrich reporting receiving grants from the CDC during the conduct of the study. Dr Knoll reported receiving grants from the CDC during the conduct of the study. Ms Schappell reported receiving grants from the CDC during the conduct of the study. Dr Meece reported receiving grants from the CDC during the conduct of the study. Ms Hanson reported receiving grants from the CDC during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was funded by grant 75D30120C08737 from the CDC (Dr Karron via Johns Hopkins University).

Role of the Funder/Sponsor: The funder 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.

Group Information: SEARCH Study Team members are listed in Supplement 2.

Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Additional Contributions: We are grateful to the SEARCH households for their dedicated participation in this study and to Annapolis Pediatrics, Columbia Medical Practice, Dundalk Pediatrics, and Johns Hopkins Community Physicians for allowing us to recruit households from their practices. We also thank the Department of Pathology, Johns Hopkins University School of Medicine, for performing the SARS-CoV-2 Roche Elecsys assays.

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