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

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

doi:10.1002/ppul.25679

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

Pediatr Pulmonol. 2021 Dec;56(12):3924-3933. doi: 10.1002/ppul.25679. Epub 2021 Sep 27.

Authors

Hala K Shafiek¹, Hanan M Abd El Lateef², Naglaa F Boraey³, Mohamed Nashat⁴, Ghada A B Abd-Elrehim³, Heba Abouzeid⁵, Sahbaa F M Hafez⁵, Hassan Shehata⁵, Ahmed A Elhewala⁵, Alsayed Abdel-Aziz⁵, Nancy M S Zeidan⁶, Mohammed M Soliman⁶, Mohammad M Sallam⁷, Abdalla M Nawara⁷, Elsayed A Elgohary⁷, Abdallah I Badr⁸, Dalia M Selim², Suzan A Razek², Batoul M Abdel Raouf², Hani A Elmikaty⁹, Lamya M Ibrahim¹⁰, Gehan H Shahin¹¹, Rehab M Nabil¹², Mohamed A M Ibrahim¹³, Hanan F Salem¹⁴, Ahmed A M Moustafa¹⁴, Naglaa A Elshehawy¹⁵, Marwa M Abdel-Aziz¹⁵, Heba H Eltrawy¹⁶, Sherif F Osman¹⁷, Rania A Fouad^{18

19}, Mona R Afify²⁰, Mohamed Y Mohamed²¹, Yousif M Yousif⁵, Aly A Yousef²², Mohamed A Arafa⁵

Affiliations

¹ Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
² Department of Pediatrics, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
³ Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt.
⁴ Department of Pediatrics, Faculty of Medicine, Aswan University, Aswan, Egypt.
⁵ Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁶ Department of Pediatrics, Faculty of Medicine, Cairo University, Egypt.
⁷ Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁸ Department of Cardiothoracic Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁹ Department of Pediatrics, National Research Centre, Cairo, Egypt.
¹⁰ Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
¹¹ Department of Clinical Pathology, Faculty of Medicine, Cairo University, Egypt.
¹² Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
¹³ Department of Clinical Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt.
¹⁴ Department of Anesthesia, Faculty of Medicine, Benha University, Banha, Egypt.
¹⁵ Department of Anathesia, Faculty of Medicine, Al Azhar University, Egypt.
¹⁶ Department of Chest Diseases, Faculty of Medicine for Girls, Al-Azhar University, Egypt.
¹⁷ Department of Radiology, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA.
¹⁸ Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
¹⁹ Department of Medical Biochemistry, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia.
²⁰ Department of Medical Microbiology and Parasitology, Faculty of Medicine, University of Jeddah, Jeddah, Saudia Arabia.
²¹ Department of Psychiatry, Faculty of Medicine, Ain-Shams University, Egypt.
²² Department of Pediatrics, Faculty of Medicine, Helwan University, Egypt.

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.

Publication types

Multicenter Study

MeSH terms

Adolescent
COVID-19* / immunology
Child
Cytokines / blood*
Egypt / epidemiology
Humans

Substances

Cytokines