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

JAMA Netw Open. 2020 Jun 1;3(6):e2010895. doi: 10.1001/jamanetworkopen.2020.10895.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Alanine Transaminase / metabolism
  • Anti-Bacterial Agents / therapeutic use
  • Antiviral Agents / therapeutic use
  • Aspartate Aminotransferases / metabolism
  • B-Lymphocytes / immunology
  • C-Reactive Protein / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • COVID-19
  • Child
  • Child, Preschool
  • China / epidemiology
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / therapy
  • Creatine Kinase, MB Form / metabolism
  • Critical Illness
  • Cytokines / immunology*
  • Female
  • Hospitals, Pediatric
  • Humans
  • Infant
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology
  • Interleukin-2 / immunology
  • Interleukin-4 / immunology
  • Interleukin-6 / immunology
  • Killer Cells, Natural / immunology
  • L-Lactate Dehydrogenase / metabolism
  • Leukocyte Count
  • Lymphocyte Count
  • Male
  • Neutrophils / immunology*
  • Pandemics
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / therapy
  • Severity of Illness Index
  • Sex Distribution
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Bacterial Agents
  • Antiviral Agents
  • Cytokines
  • IL10 protein, human
  • IL2 protein, human
  • IL4 protein, human
  • IL6 protein, human
  • Interleukin-2
  • Interleukin-6
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • C-Reactive Protein
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Creatine Kinase, MB Form