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

Shafiek, Hala K; El Lateef, Hanan M Abd; Boraey, Naglaa F; Nashat, Mohamed; Abd-Elrehim, Ghada A B; Abouzeid, Heba; Hafez, Sahbaa F M; Shehata, Hassan; Elhewala, Ahmed A; Abdel-Aziz, Alsayed; Zeidan, Nancy M S; Soliman, Mohammed M; Sallam, Mohammad M; Nawara, Abdalla M; Elgohary, Elsayed A; Badr, Abdallah I; Selim, Dalia M; Razek, Suzan A; Abdel Raouf, Batoul M; Elmikaty, Hani A; Ibrahim, Lamya M; Shahin, Gehan H; Nabil, Rehab M; Ibrahim, Mohamed A M; Salem, Hanan F; Moustafa, Ahmed A M; Elshehawy, Naglaa A; Abdel-Aziz, Marwa M; Eltrawy, Heba H; Osman, Sherif F; Fouad, Rania A; Afify, Mona R; Mohamed, Mohamed Y; Yousif, Yousif M; Yousef, Aly A; Arafa, Mohamed A

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 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 SARS-CoV-2 in respiratory fluid specimens was detected by real-time reverse-transcriptase-PCR (RT-PCR). 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% CI: 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. This article is protected by copyright. All rights reserved.