Cytokine profile in Egyptian children and adolescents with COVID-19 pneumonia: A multicenter study

Abstract

Background: To date, the cytokine profile in children and adolescent with novel coronavirus disease 2019 (COVID-19) has not been reported.

Objectives: We investigated serum levels of a panel of key cytokines in children and adolescent with COVID-19 pneumonia with a primary focus on "cytokine storm" cytokines such as interleukin (IL)-1β, IL-6, IL-17, IL-2, IL-4, IL-10, interferon (IFN-γ), tumor necrosis factor (TNF)-α, and two chemokines interferon-inducible protein-10 (IP-10) and IL-8. We also studied whether these cytokines could be potential markers for illness severity in COVID-19 pneumonia.

Methods: Ninety-two symptomatic patients aged less than 18 years with confirmed COVID-19 pneumonia and 100 well-matched healthy controls were included in this multi-center study. For all patients, the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory fluid specimens was detected by real-time reverse-transcriptase polymerase chain reaction. We measured serum concentrations of studied cytokines by using flow cytometry.

Results: Patients with COVID-19 had significantly higher median IL-1β, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 serum levels than did control children (all p < 0.01). Patients with severe COVID-19 pneumonia had significantly higher median IL-1β, IL-6, and IP-10 serum levels as compared with those with moderate COVID-19 pneumonia; all p < 0.01. ROC analysis revealed that three of the studied markers (IL-6, IL-1β, and IP-10) could predict severe COVID-19 pneumonia cases with the largest AUC for IL-6 of 0.893 (95% confidence interval: 0.84-0.98; p < 0.01).

Conclusion: Our study shows that pediatric patients with COVID-19 pneumonia have markedly elevated serum IL-1β, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 levels at the initial phase of the illness indicating a cytokine storm following SARS-CoV-2 infection. Moreover, serum IL-6, IL-1β, and IP-10 concentrations were independent predictors for severe COVID-19 pneumonia.

Keywords: adolescents; children; coronavirus disease 2019 (COVID-19); cytokine profile; pneumonia.

Figure 1

(A) Serum IL‐1β level among COVID‐19 patients with moderate and severe pneumonia and control group. (B) Serum IL‐6 level among COVID‐19 patients with moderate and severe pneumonia and control group. (C) Serum IP‐10 level among COVID‐19 patients with moderate and severe pneumonia and control group. COVID‐19, coronavirus disease‐2019; IL, interleukin; IP‐10, interferon‐inducible protein‐10 [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

(A) Performance of ROC curves for predicting severe COVID‐19 pneumonia. (B) ROC curves showing performance of a different combinations of serum cytokines for diagnosis of severe COVID‐19 pneumonia. COVID‐19, coronavirus disease‐2019; ROC, receiver operating characteristic [Color figure can be viewed at wileyonlinelibrary.com]