SEX- AND AGE-RELATED FEATURES OF ENDOTHELIN-1 LEVELS IN CHILDREN INFECTED WITH SARS-COV-2

Authors

DOI:

https://doi.org/10.11603/24116-4944.2025.2.15818

Keywords:

endothelin-1, COVID-19, MIS-C, children

Abstract

The aim of the study − to determine age- and sex-related differences in endothelin-1 (ET-1) levels in children with coronavirus disease (COVID-19) and multisystem inflammatory syndrome in children (MIS-C).

Materials and Methods. The study included 200 children with COVID-19 and 40 children with MIS-C. The median age of patients with COVID-19 was 3.00 (0.75; 9.00) years, whereas in the MIS-C group it was 7.50 (3.88; 10.00) years (p<0.05). The groups did not differ by sex distribution (p>0.05). ET-1 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) with the Human ET-1 (Endothelin-1) ELISA Kit.

Results and Discussion. ET-1 levels in children with MIS-C (25.76 (18.41; 33.75) pg/mL) were significantly higher than in those with acute SARS-CoV-2 infection (9.95 (5.66; 12.96) pg/mL) (p<0.001). In the MIS-C group, boys had significantly higher ET-1 levels compared with girls − 31.50 (22.27; 39.75) pg/mL and 15.22 (10.43; 22.09) pg/mL, respectively (p<0.05). No sex-related differences were found in the COVID-19 group (p>0.05). Among children with COVID-19, ET-1 levels increased with age (B=1.34; SE=0.66; p=0.047). In the MIS-C group, both male sex (B=-25.41; SE=8.06; p=0.007) and older age (B=11.10; SE=3.14; p=0.003) were associated with higher ET-1 concentrations.

Conclusions. The study results demonstrated significantly higher ET-1 levels in children with MIS-C compared with those with COVID-19. The data highlight the important role of sex and age factors in the development of endothelial dysfunction in pediatric patients with COVID-19 and MIS-C, which may have practical implications for predicting endothelial involvement in children.

Author Biographies

K. V. Kozak, I. Horbachevsky Ternopil National Medical University

Candidate of Medical Science, Associate Professor

H. A. Pavlyshyn, I. Horbachevsky Ternopil National Medical University

Doctor  of  Medical  Science, Professor

References

Turgunova, L., Mekhantseva, I., Laryushina, Y., Alina, A., Bacheva, I., Zhumadilova, Z., & Turmukhambetova, A. (2023). The Association of Endothelin-1 with Early and Long-Term Mortality in COVID-19. Journal of Personalized Medicine, 13(11). 1558. DOI: 10.3390/jpm13111558. DOI: https://doi.org/10.3390/jpm13111558

Xu, S., Ilyas, I., & Weng, J. (2023). Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies. Acta Pharmacologica Sinica, 44(4). 695-709. DOI: 10.1038/s41401-022-00998-0. DOI: https://doi.org/10.1038/s41401-022-00998-0

Aljadah, M., Khan, N., Beyer, A.M., Chen, Y., Blanker, A., & Widlansky, M.E. (2024). Clinical Implications of COVID-19-Related Endothelial Dysfunction. JACC: Advances, 3(8). 101070. DOI: 10.1016/j.jacadv.2024.101070. DOI: https://doi.org/10.1016/j.jacadv.2024.101070

Ruhl, L., Pink, I., Kühne, J.F., Beushausen, K., Keil, J., Christoph, S., ... & Falk, C.S. (2021). Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks. Signal Transduction and Targeted Therapy, 6(1). 418. DOI: 10.1038/s41392-021-00819-6. DOI: https://doi.org/10.1038/s41392-021-00819-6

Vassiliou, A.G., Vrettou, C.S., Keskinidou, C., Dimopoulou, I., Kotanidou, A., & Orfanos, S.E. (2023). Endotheliopathy in Acute COVID-19 and Long COVID. International Journal of Molecular Sciences, 24(9). 8237. DOI: 10.3390/ijms24098237. DOI: https://doi.org/10.3390/ijms24098237

Prepeliuc, C.S., Pasăre, M.A., Grigoriu, M.G., Miftode, I.L., Miftode, R. Ștefan, Vâță, A., ... & Miftode, E.G. (2025). The Involvement of Endothelin-1 in Sepsis and Organ Dysfunction – A Novel Biomarker in Patient Assessment. Biomedicines, 13(10). 2480. DOI: 10.3390/biomedicines13102480. DOI: https://doi.org/10.3390/biomedicines13102480

Abraham, G.R., Kuc, R.E., Althage, M., Greasley, P.J., Ambery, P., Maguire, J.J., ... & Davenport, A.P. (2022). Endothelin-1 is increased in the plasma of patients hospitalised with Covid-19. Journal of Molecular and Cellular Cardiology, 167(January). 92-96. DOI: 10.1016/j.yjmcc.2022.03.007. DOI: https://doi.org/10.1016/j.yjmcc.2022.03.007

Banecki, K.M.R.M., & Dora, K.A. (2023). Endothelin-1 in Health and Disease. International Journal of Molecular Sciences, 24(14). 11295. DOI: 10.3390/ijms241411295. DOI: https://doi.org/10.3390/ijms241411295

Shaw, J.A., Meiring, M., Snyders, C., Everson, F., Sigwadhi, L.N., Ngah, V., … & Nyasulu, P.S. (2023). Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort. Frontiers in Immunology, 14. DOI: 10.3389/fimmu.2023.1219097. DOI: https://doi.org/10.3389/fimmu.2023.1219097

Graciano-Machuca, O., Villegas-Rivera, G., López-Pérez, I., Macías-Barragán, J., & Sifuentes-Franco, S. (2021). Multisystem Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Role of Oxidative Stress. Frontiers in Immunology, 12. DOI: 10.3389/fimmu.2021.723654. DOI: https://doi.org/10.3389/fimmu.2021.723654

Jin, Y., Ji, W., Yang, H., Chen, S., Zhang, W., & Duan, G. (2020). Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches. In Signal Transduction and Targeted Therapy (Vol. 5, Issue 1). Springer Nature. DOI: 10.1038/s41392-020-00454-7. DOI: https://doi.org/10.1038/s41392-020-00454-7

Perrone, S., Cannavò, L., Manti, S., Rulli, I., Buonocore, G., Esposito, S., & Gitto, E. (2022). Pediatric Multisystem Syndrome Associated with SARS-CoV-2 (MIS-C): The Interplay of Oxidative Stress and Inflammation. International Journal of Molecular Sciences, 23(21). 12836. DOI: 10.3390/ijms232112836. DOI: https://doi.org/10.3390/ijms232112836

Nabeh, O.A., Matter, L.M., Khattab, M.A., & Esraa Menshawey. (2021). The possible implication of endothelin in the pathology of COVID-19-induced pulmonary hypertension. Pulmonary Pharmacology & Therapeutics, 71. 102082. DOI: 10.1016/j.pupt.2021.102082. DOI: https://doi.org/10.1016/j.pupt.2021.102082

Matsuishi, Y., Mathis, B.J., Shimojo, N., Subrina, J., Okubo, N., & Inoue, Y. (2021). Severe COVID-19 Infection Associated with Endothelial Dysfunction Induces Multiple Organ Dysfunction: A Review of Therapeutic Interventions. Biomedicines, 9(3). 279. DOI: 10.3390/biomedicines9030279. DOI: https://doi.org/10.3390/biomedicines9030279

World Health Organization (n. d.). Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19. Retrieved July 20, 2025, from https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19.

Stauffer, B.L., Westby, C.M., Greiner, J.J., Van Guilder, G.P., & DeSouza, C.A. (2010). Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 298(2). R261-R265. DOI: 10.1152/ajpregu.00626.2009. DOI: https://doi.org/10.1152/ajpregu.00626.2009

Kuczmarski, A.V., Welti, L.M., Moreau, K.L., & Wenner, M.M. (2021). ET-1 as a Sex-Specific Mechanism Impacting Age-Related Changes in Vascular Function. Frontiers in Aging, 2. DOI: 10.3389/fragi.2021.727416. DOI: https://doi.org/10.3389/fragi.2021.727416

Bilsel, A. (2000). 17β-Estradiol modulates endothelin-1 expression and release in human endothelial cells. Cardiovascular Research, 46(3). 579-584. DOI: 10.1016/S0008-6363(00)00046-8. DOI: https://doi.org/10.1016/S0008-6363(00)00046-8

Wilbert-Lampen, U., Seliger, C., Trapp, A., Straube, F., & Plasse, A. (2005). Female Sex Hormones Decrease Constitutive Endothelin-1 Release via Endothelial Sigma-1/Cocaine Receptors: An Action Independent of the Steroid Hormone Receptors. Endothelium, 12(4). 185-191. DOI: 10.1080/10623320500227275. DOI: https://doi.org/10.1080/10623320500227275

Allalou, A., Peng, J., Robinson, G.A., Marruganti, C., D’Aiuto, F., Butler, G., ... & Ciurtin, C. (2023). Impact of puberty, sex determinants and chronic inflammation on cardiovascular risk in young people. Frontiers in Cardiovascular Medicine, 10. DOI: 10.3389/fcvm.2023.1191119. DOI: https://doi.org/10.3389/fcvm.2023.1191119

Pearson, L.J., Yandle, T.G., Nicholls, M.G., & Evans, J.J. (2008). Regulation of endothelin-1 release from human endothelial cells by sex steroids and angiotensin-II. Peptides, 29(6). 1057-1061. DOI: 10.1016/j.peptides.2008.02.003. DOI: https://doi.org/10.1016/j.peptides.2008.02.003

Wójcik, M., Starzyk, J.B., Drożdż, M., & Drożdż, D. (2023). Effects of Puberty on Blood Pressure Trajectories – Underlying Processes. Current Hypertension Reports, 25(7). 117-125. DOI: 10.1007/s11906-023-01241-9. DOI: https://doi.org/10.1007/s11906-023-01241-9

Babcock, M.C., DuBose, L.E., Hildreth, K.L., Stauffer, B.L., Kohrt, W.M., Wenner, M.M., & Moreau, K.L. (2025). Endothelial dysfunction in middle-aged and older men with low testosterone is associated with elevated circulating endothelin-1. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 328(3). R253-R261. DOI: 10.1152/ajpregu.00218.2024. DOI: https://doi.org/10.1152/ajpregu.00218.2024

Yoshibayashi, M., Nishioka, K., Nakao, K., Saito, Y., Temma, S., Matsumura, M., ... & Mikawa, H. (1991). Plasma Endothelin Levels in Healthy Children. Journal of Cardiovascular Pharmacology, 17. S404-405. DOI: 10.1097/00005344-199100177-00113 DOI: https://doi.org/10.1097/00005344-199100177-00113

Published

2025-12-15

How to Cite

Kozak, K. V., & Pavlyshyn, H. A. (2025). SEX- AND AGE-RELATED FEATURES OF ENDOTHELIN-1 LEVELS IN CHILDREN INFECTED WITH SARS-COV-2. Actual Problems of Pediatrics, Obstetrics and Gynecology, (2), 79–84. https://doi.org/10.11603/24116-4944.2025.2.15818

Issue

Section

PEDIATRICS