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Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China

Educational Objective
To understand clinical and immune features of hospitalized pediatric patients with COVID-19
1 Credit CME
Key Points

Question  What are the immunologic features of pediatric patients with pneumonia caused by coronavirus disease 2019 (COVID-19)?

Findings  In this single-center case series involving 157 pediatric patients with COVID-19, systemic inflammation rarely occurred. Patients with moderate disease had higher interleukin 10 levels and lower neutrophil levels than patients with mild disease.

Meaning  The results of this study suggest that dysregulation of immune response may be involved in the pathologic process of COVID-19; gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of severe acute respiratory syndrome coronavirus 2 infection could be important for the clinical management of COVID-19.

Abstract

Importance  The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce.

Objective  To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients.

Design, Setting, and Participants  This single-center case series included 157 pediatric patients admitted to Wuhan Children’s Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020.

Exposures  Documented SARS-CoV-2 infection.

Main Outcomes and Measures  Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020.

Results  Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/μL [1680/μL-3510/μL] vs 3120/μL [2040/μL-4170/μL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, −0.3579; AST: r, −0.5280; CK-MB activity: r, −0.4786; LDH: r, −0.4984; and neutrophil to lymphocyte ratio, ALT: r, −0.1893; AST: r, −0.3912; CK-MB activity: r, −0.3428; LDH: r, −0.3234), while counts of lymphocytes, CD4+ T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4+ T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794).

Conclusions and Relevance  In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.

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Article Information

Accepted for Publication: May 6, 2020.

Published: June 3, 2020. doi:10.1001/jamanetworkopen.2020.10895

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Wu H et al. JAMA Network Open.

Corresponding Author: Yun Xiang, PhD, Department of Laboratory Medicine (xiangyun5272008@163.com), and Jianbo Shao, PhD, Department of Radiology (shaojb2002@sina.com), Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China.

Author Contributions: Dr Xiang had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Wu, Zhu, Yuan, and Yao contributed equally to this work.

Concept and design: Xiang.

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

Drafting of the manuscript: Wu, Zhu, Yuan, Shen, Wang, Shao.

Critical revision of the manuscript for important intellectual content: Zhu, Yao, Luo, Xiang.

Statistical analysis: Wu, Zhu, Yao, Luo.

Obtained funding: Wu.

Administrative, technical, or material support: Wu.

Supervision: Shao, Xiang.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by grant WJ2019H379 from the Natural Science Foundation of Hubei Province, China and grants WX19Q32 and WX17B11 from the Natural Science Foundation of Wuhan Municipal Health Commission.

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.

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