FEATURES OF PRO-INFLAMMATORY CYTOKINES (IL-6 AND TNF-α) IN CHILDREN WITH COVID-19
DOI:
https://doi.org/10.11603/24116-4944.2024.1.14755Keywords:
COVID-19, children, interleukin-6, tumor necrosis factor-alfaAbstract
The aim of the study – to evaluate IL-6 and TNF-a levels in children with COVID-19 and their dependence on the severity of the disease
Materials and Methods. 112 children with COVID-19, aged 1 month to 18 years, who were hospitalized at the Department of Infectious Diseases of Ternopil City Children's Hospital were examined. The level of IL-6 and TNF-a in serum samples was determined by enzyme-linked immunosorbent assay using standard kits (BT Lab, China).
Results and Discussion. The average age of children was (7.04±5.75) years (95% CI 5.96−8.12). Regarding disease severity, 57 children (42.23%) had a mild course of the disease, 43 children (31.86%) had a moderate course, and 12 children (8.88%) had a severe course. The concentration of IL-6 in children with a mild course of COVID-19 was 80.36 ng/ml; with a moderate course – 101 ng/ml; with a severe course – 151.90 ng/ml (р<0.001). The level of TNF-a in mild COVID-19 was 56.7 ng/ml; 97.73 ng/ml – in moderate disease severity, and 182.42 ng/ml – in severe cases (р<0.001).
Conclusions. The level of cytokines IL-6 and TNF-a in children with COVID-19 depends on the severity of the disease. Patients with severe COVID-19 have significantly higher levels of IL-6 and TNF-α compared to mild and moderate COVID-19. Correlative relationships between high levels of IL-6, TNF-α and C-reactive protein, ESR, and lymphocytes were found in children with COVID-19. No gender patterns were found in relation to cytokines (IL-6, TNF-α) and age-specific characteristics in relation to TNF-α indicators.
References
World Health Organization. Rolling updates on coronavirus disease (COVID-19). Retrieved from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019.
Wiersinga, W. J., Rhodes, A., Cheng, A. C., Peacock, S. J., & Prescott, H. C. (2020). Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. Jama, 324(8), 782-793. DOI:10.1001/jama.2020.12839.
Yang, L., Liu, S., Liu, J., Zhang, Z., Wan, X., Huang, B., ... & Zhang, Y. (2020). COVID-19: immunopathogenesis and immunotherapeutics. Signal transduction and targeted therapy, 5(1), 128. DOI: 10.1038/s41392-020-00243-2.
Gu, Y., Wang, D., Chen, C., Lu, W., Liu, H., Lv, T., ... & Zhang, F. (2021). PaO2/FiO2 and IL-6 are risk factors of mortality for intensive care COVID-19 patients. Scientific reports, 11(1), 7334. DOI: 10.1038/s41598-021-86676-3.
Chen, G., Wu, D. I., Guo, W., Cao, Y., Huang, D., Wang, H., ... & Ning, Q. (2020). Clinical and immunological features of severe and moderate coronavirus disease 2019. The Journal of clinical investigation, 130(5), 2620-2629. DOI: 10.1172/JCI137244.
Del Valle, D. M., Kim-Schulze, S., Huang, H. H., Beckmann, N. D., Nirenberg, S., Wang, B., ... & Gnjatic, S. (2020). An inflammatory cytokine signature predicts COVID-19 severity and survival. Nature medicine, 26(10), 1636-1643. DOI: 10.1038/s41591-020-1051-9.
Niculet, E., Chioncel, V., Elisei, A. M., Miulescu, M., Buzia, O. D., Nwabudike, L. C., ... & Tatu, A. L. (2021). Multifactorial expression of IL 6 with update on COVID 19 and the therapeutic strategies of its blockade. Experimental and therapeutic medicine, 21(3), 1-1. DOI: 10.3892/etm.2021.9693.
Villar-Fincheira, P., Sanhueza-Olivares, F., Norambuena-Soto, I., Cancino-Arenas, N., Hernandez-Vargas, F., Troncoso, R., ... & Chiong, M. (2021). Role of interleukin-6 in vascular health and disease. Frontiers in molecular biosciences, 8, 641734. DOI: 10.3389/fmolb.2021.641734.
Majidpoor, J., & Mortezaee, K. (2022). Interleukin-6 in SARS-CoV-2 induced disease: Interactions and therapeutic applications. Biomedicine & Pharmacotherapy, 145, 112419. DOI: 10.1016/j.biopha.2021.112419.
Tagarro, A., Epalza, C., Santos, M., Sanz-Santaeufemia, F. J., Otheo, E., Moraleda, C., & Calvo, C. (2021). Screening and severity of coronavirus disease 2019 (COVID-19) in children in Madrid, Spain. JAMA pediatrics, 175(3), 316-317. DOI: 10.1001/jamapediatrics.2020.1346.
May, L. T., Viguet, H., Kenney, J. S., Ida, N., Allison, A. C., & Sehgal, P. B. (1992). High levels of “complexed” interleukin-6 in human blood. Journal of Biological Chemistry, 267(27), 19698-19704. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/1527089/.
Dzis, I. Ye., Tomashevskaia, A. Ya., Dzis, Ye. I., & Danysh, O. Y. (2017). Prohnostychne znachennia markeriv systemnoho zapalennia dlia perebihu nehodzhkinskykh limfom i khronichnoi limfotsytarnoi leikemii [Prognostic value of markers of systemic inflammation for the course of non-Hodgkin's lymphoma and chronic lymphocytic leukemia]. Ukrainskyi medychnyi chasopys – Ukrainian medical journal , (3), 153-156. Retrieved from: http://nbuv.gov.ua/UJRN/UMCh_2017_3_35 [in Ukrainian].
Del Valle, D. M., Kim-Schulze, S., Huang, H. H., Beckmann, N. D., Nirenberg, S., Wang, B., ... & Gnjatic, S. (2020). An inflammatory cytokine signature predicts COVID-19 severity and survival. Nature medicine, 26(10), 1636-1643. DOI: 10.1038/s41591-020-1051-9.
Taghiloo, S., Soltanshahi, M., Aliyali, M., Abedi, S., Mehravaran, H., Ajami, A., & Asgarian-Omran, H. (2021). Cytokine profiling in Iranian patients with COVID-19; association with clinical severity. Iranian Journal of Immunology, 18(1), 54-64. DOI: 10.22034/IJI.2021.87630.1810.
Palacios, Y., & Chavez-Galan, L. (2022). Immunosuppressant therapies in COVID-19: is the TNF axis an alternative?. Pharmaceuticals, 15(5), 616. DOI: 10.3390/ph15050616.
Liu, B., Li, M., Zhou, Z., Guan, X., & Xiang, Y. (2020). Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?. Journal of autoimmunity, 111, 102452. DOI: 10.1016/j.jaut.2020.102452.
Vultaggio, A., Vivarelli, E., Virgili, G., Lucenteforte, E., Bartoloni, A., Nozzoli, C., ... & Matucci, A. (2020). Prompt predicting of early clinical deterioration of moderate-to-severe COVID-19 patients: usefulness of a combined score using IL-6 in a preliminary study. The Journal of Allergy and Clinical Immunology: In Practice, 8(8), 2575-2581. DOI: 10.1016/j.jaip.2020.06.013.
Remap-Cap Investigators. (2021). Interleukin-6 receptor antagonists in critically ill patients with Covid-19. New England Journal of Medicine, 384(16), 1491-1502. DOI: 10.1056/NEJMoa2100433.
Lasky, J. A., Fuloria, J., Morrison, M. E., Lanier, R., Naderer, O., Brundage, T., & Melemed, A. (2021). Design and rationale of a randomized, double-blind, placebo-controlled, phase 2/3 study evaluating dociparstat in acute lung injury associated with severe COVID-19. Advances in Therapy, 38, 782-791. DOI: 10.1007/s12325-020-01539-z.
Biran, N., Ip, A., Ahn, J., Go, R. C., Wang, S., Mathura, S., ... & Goldberg, S. L. (2020). Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study. The Lancet Rheumatology, 2(10), e603-e612. DOI: 10.1016/S2665-9913(20)30277-0.
Del Valle, D. M., Kim-Schulze, S., Huang, H. H., Beckmann, N. D., Nirenberg, S., Wang, B., ... & Gnjatic, S. (2020). An inflammatory cytokine signature predicts COVID-19 severity and survival. Nature medicine, 26(10), 1636-1643. DOI: 10.1038/s41591-020-1051-9.
Mokhtari, T., Hassani, F., Ghaffari, N., Ebrahimi, B., Yarahmadi, A., & Hassanzadeh, G. (2020). COVID-19 and multiorgan failure: A narrative review on potential mechanisms. Journal of molecular histology, 51, 613-628. DOI: 10.1007/s10735-020-09915-3.].
Chen, X., Zhou, J., Chen, C., Hou, B., Ali, A., Li, F., ... & Men, D. (2021). Consecutive monitoring of interleukin-6 is needed for COVID-19 patients. Virologica Sinica, 36, 1093-1096. DOI: 10.1007/s12250-021-00425-4.
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., ... & Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223), 497-506. DOI: 10.1016/S0140-6736(20)30183-5.
Mauad, T., Duarte-Neto, A. N., da Silva, L. F. F., de Oliveira, E. P., de Brito, J. M., do Nascimento, E. C. T., ... & Dolhnikoff, M. (2021). Tracking the time course of pathological patterns of lung injury in severe COVID-19. Respiratory Research, 22(1), 1-11. DOI: 10.1186/s12931-021-01628-9.
Niculet, E., Chioncel, V., Elisei, A. M., Miulescu, M., Buzia, O. D., Nwabudike, L. C., ... & Tatu, A. L. (2021). Multifactorial expression of IL 6 with update on COVID 19 and the therapeutic strategies of its blockade. Experimental and therapeutic medicine, 21(3), 1-1. DOI: 10.3892/etm.2021.9693.
Herold, T., Jurinovic, V., Arnreich, C., Lipworth, B. J., Hellmuth, J. C., von Bergwelt-Baildon, M., ... & Weinberger, T. (2020). Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. Journal of Allergy and Clinical Immunology, 146(1), 128-136. DOI: 10.1016/j.jaci.2020.05.008.
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., ... & Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223), 497-506. DOI: 10.1016/S0140-6736(20)30183-5.
Mauad, T., Duarte-Neto, A. N., da Silva, L. F. F., de Oliveira, E. P., de Brito, J. M., do Nascimento, E. C. T., ... & Dolhnikoff, M. (2021). Tracking the time course of pathological patterns of lung injury in severe COVID-19. Respiratory Research, 22(1), 1-11. DOI: 10.1186/s12931-021-01628-9.
Niculet, E., Chioncel, V., Elisei, A. M., Miulescu, M., Buzia, O. D., Nwabudike, L. C., ... & Tatu, A. L. (2021). Multifactorial expression of IL 6 with update on COVID 19 and the therapeutic strategies of its blockade. Experimental and therapeutic medicine, 21(3), 1-1. DOI: 10.3892/etm.2021.9693.
Herold, T., Jurinovic, V., Arnreich, C., Lipworth, B. J., Hellmuth, J. C., von Bergwelt-Baildon, M., ... & Weinberger, T. (2020). Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. Journal of Allergy and Clinical Immunology, 146(1), 128-136. DOI: 10.1016/j.jaci.2020.05.008.
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