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

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.

Figure 1.. Neutrophil to Lymphocyte Ratio (NLR) and Neutrophil to CD8⁺ T Cell Ratio (N8R) in Pediatric Patients With Coronavirus Disease 2019

Comparisons of NLR with N8R between 60 mild cases and 88 moderate cases. Boxes represent medians and interquartile ranges, with whiskers indicating 10% to 90% range. Dots represent patients who fell outside the 10% to 90% range. Data were analyzed using Mann-Whitney test.

Figure 2.. Spearman Rank Correlation Coefficient (ρ) Analysis Between Immune Features and Biochemical Indexes

Orange dots indicate a positive association, light blue dots indicate a negative association, and dark blue dots indicate other immune indices. ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; CK-MB, creatine kinase MB; Ig, immunoglobulin; IL-10, interleukin 10; LDH, lactate dehydrogenase; LYM, lymphocytes; NK, natural killer; NLR, neutrophil to lymphocyte ratio.