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Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China.
JAMA Netw Open. 2020 06 01; 3(6):e2010895.JN

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.

Authors+Show Affiliations

Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Health Care Department, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Clinical Laboratory, Tianjin Medical University General Hospital, Tianjin, China.Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Radiology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32492165

Citation

Wu, Huan, et al. "Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China." JAMA Network Open, vol. 3, no. 6, 2020, pp. e2010895.
Wu H, Zhu H, Yuan C, et al. Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China. JAMA Netw Open. 2020;3(6):e2010895.
Wu, H., Zhu, H., Yuan, C., Yao, C., Luo, W., Shen, X., Wang, J., Shao, J., & Xiang, Y. (2020). Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China. JAMA Network Open, 3(6), e2010895. https://doi.org/10.1001/jamanetworkopen.2020.10895
Wu H, et al. Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China. JAMA Netw Open. 2020 06 1;3(6):e2010895. PubMed PMID: 32492165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China. AU - Wu,Huan, AU - Zhu,Hongmin, AU - Yuan,Chunhui, AU - Yao,Cong, AU - Luo,Wei, AU - Shen,Xin, AU - Wang,Jun, AU - Shao,Jianbo, AU - Xiang,Yun, Y1 - 2020/06/01/ PY - 2020/6/4/entrez PY - 2020/6/4/pubmed PY - 2020/6/12/medline SP - e2010895 EP - e2010895 JF - JAMA network open JO - JAMA Netw Open VL - 3 IS - 6 N2 - 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. SN - 2574-3805 UR - https://www.unboundmedicine.com/medline/citation/32492165/Clinical_and_Immune_Features_of_Hospitalized_Pediatric_Patients_With_Coronavirus_Disease_2019__COVID_19__in_Wuhan_China_ L2 - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2020.10895 DB - PRIME DP - Unbound Medicine ER -