Clinical Research
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Ağır COVID-19 Hastalarında Serum IL-33 Düzeylerinin Pulmoner Fibrozis ile İlişkisinin Değerlendirilmesi

Year 2023, Volume: 6 Issue: 1, 1 - 13, 19.06.2023

Abstract

Bu çalışmanın amacı, COVID-19 tanısı alarak, takip edilen hastalarda, pulmoner fibrozis gelişiminde IL-33’ün prediktif değerini araştırmaktır. Çalışmamız Konya Eğitim ve Araştırma Hastanesi, Yoğun Bakım Ünitesinde takip edilmiş COVID-19 kesin tanılı hastalar üzerinde yapılmıştır. IL-33 konsantrasyonlarını ölçmek için ELISA yöntemi kullanılmıştır. Hastaların, beyaz kan hücresi (WBC), hemoglobin değeri, trombosit (PLT) ve lenfosit (LNF) sayıları; D-dimer ve fibrinojen gibi koagülasyon ile ilişkili parametreleri; C-reaktif protein (CRP), albümin (Alb), ürik asit, ferritin (FER) ve arter kan gazlarından laktat ve pO2 sonuçları çalışmaya dahil edilmiştir. Sitokin düzeyleri ile klinik, biyokimyasal, radyografik verilerin korelasyonları analiz edilmiştir. Şiddetli hastalığı olan COVID-19 hastalarında önemli ölçüde daha yüksek serum IL-33 konsantrasyonu olduğu bulunmuştur. IL-33'ün serum değerleri ile CRP, CRP/Alb oranı ve ürik asit arasında orta düzeyde pozitif korelasyon saptanmıştır. Subplevral bant varlığında IL-33 düzeylerinin anlamlı düzeyde yüksek, FER ve PLT düzeylerinin anlamlı düzeyde düşük olduğu görülmüştür. Fibrotik şerit varlığında IL-33 düzeylerinin anlamlı düzeyde yüksek; WBC, PLT ve PLT/LNF oranının anlamlı düzeyde düşük olduğu görülmüştür. ROC analizi sonuçlarına göre IL-33 için sensitivite %97, spesifisite %86 ve AUC değeri 1,97 olarak bulunmuştur. IL-33, COVID-19'un bazı radyolojik ve laboratuvar parametreleriyle ilişkili ve COVID-19'da umut verici bir belirteç olarak belirlendiği için terapötik bir hedefi temsil edebilir.

Supporting Institution

Konya Eğitim ve Araştırma Hastanesi, Tıpta Uzmanlık Eğitim Kurulu

Project Number

39-04 sayı

Thanks

Bu çalışmaya destek ve katkılarından dolayı Konya Eğitim ve Araştırma Hastanesi, Tıpta Uzmanlık Eğitim Kurulu'na teşekkür ederiz.

References

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  • Lippi, G., Plebani, M., & Henry, B. M. (2020). Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta, 506, 145-148. https://doi.org/10.1016/j.cca.2020.03.022
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Evaluation of The Relationship Between Serum IL-33 Levels and Pulmonary Fibrosis in Severe COVID-19 Patients

Year 2023, Volume: 6 Issue: 1, 1 - 13, 19.06.2023

Abstract

The aim of this study is to investigate the predictive value of IL-33 in the development of pulmonary fibrosis in patients diagnosed with COVID-19 and followed up. Our study was carried out on patients with a definitive diagnosis of COVID-19 who were followed up in the Intensive Care Unit of Konya Training and Research Hospital. ELISA method was used to measure IL-33 concentrations. White blood cell (WBC), hemoglobin value, platelet (PLT) and lymphocyte (LNF) counts of the patients; coagulation-related parameters such as D-dimer and fibrinogen; C-reactive protein (CRP), albumin (Alb), uric acid, ferritin (FER) and lactate and pO2 results from arterial blood gases were included in the study. Correlations of cytokine levels with clinical, biochemical and radiographic data were analyzed. We found that COVID-19 patients with severe disease had a significantly higher serum IL-33 concentration. A moderate positive correlation was found between serum values of IL-33 and CRP, CRP/Alb ratio and uric acid. In the presence of subpleural band, IL-33 levels were found to be significantly higher, and FER and PLT levels were significantly lower. In the presence of fibrotic stripe, IL-33 levels were significantly higher; WBC, PLT and PLT/LNF ratios were found to be significantly lower. According to the results of the ROC analysis, the sensitivity for IL-33 was 97%, the specificity was 86%, and the AUC value was 1.97. IL-33 is associated with some radiological and laboratory parameters of COVID-19 and is a promising marker in COVID-19 and may also represent a therapeutic target.

Project Number

39-04 sayı

References

  • Atalay, E., Çelik, S., & Kahraman, İ. (2021). Investigation of the Effect of COVID-19 on Kidney Functions. Dünya Sağlık ve Tabiat Bilimleri Dergisi, 4(2), 75-79.
  • Beltrán, C. J., Núñez, L. E., Díaz-Jiménez, D., Farfan, N., Candia, E., Heine, C. … Hermoso, M. A. (2010). Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis, 16(7), 1097-1107. https://doi.org/10.1002/ibd.21175
  • Butt, M. U., & Jabri, A. (2019). Azithromycin-Induced Thrombocytopenia: A Rare Etiology of Drug-Induced Immune Thrombocytopenia. Case Reports in Medicine, 2019, 1(3). 6109831. https://doi.org/10.1155/2019/6109831
  • Carriere, V., Roussel, L., Ortega, N., Lacorre, D. A., Americh, L., Aguilar, L. … Girard, J. P. (2007). IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci U S A, 104(1), 282-287. https://doi.org/10.1073/pnas.0606854104
  • Cayrol, C., & Girard, J. P. (2018). Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. Immunological reviews, 281(1), 154-168. https://doi.org/10.1111/imr.12619
  • Channappanavar, R., & Perlman, S. (2017). Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol, 39(5), 529-539. https://doi.org/10.1007/s00281-017-0629-x
  • Demir, D., Öcal, F., Abanoz, M., & Dermenci, H. (2014). A case of thrombocytopenia associated with the use of hydroxychloroquine following open heart surgery. Int J Surg Case Rep, 5(12), 1282-1284. https://doi.org/10.1016/j.ijscr.2014.11.052
  • Drake LY, Kita H. (2017). IL-33: biological properties, functions, and roles in airway disease. Immunol Rev., 278(1):173-184. https://doi.org/10.1111/imr.12552.
  • Fan, B. E., Chong, V. C. L., Chan, S. S. W., Lim, G. H., Lim, K. G. E., Tan, G. B. … Ong, K. H. (2020). Hematologic parameters in patients with COVID-19 infection. Am J Hematol, 95(6), E131-e134. https://doi.org/10.1002/ajh.25774
  • Gomez-Cadena, A., Spehner, L., Kroemer, M., Khelil, M. B., Bouiller, K., Verdeil, G. … Jandus, C. (2021). Severe COVID-19 patients exhibit an ILC2 NKG2D(+) population in their impaired ILC compartment. Cell Mol Immunol, 18(2), 484-486. https://doi.org/10.1038/s41423-020-00596-2
  • Güçlü, E., & Kocayiğit, H. (2020). Effect of COVID-19 on platelet count and its indices. Revista da Associação Médica Brasileira, 66(8), 1122-1127. https://doi.org/10.1590/1806-9282.66.8.1122
  • Hasan, A., Al-Ghimlas, F., Warsame, S., Al-Hubail, A., Ahmad, R., Bennakhi, A. … Dermime, S. (2014). IL-33 is negatively associated with the BMI and confers a protective lipid/metabolic profile in non-diabetic but not diabetic subjects. BMC Immunol, 15, 19. https://doi.org/10.1186/1471-2172-15-19
  • Keleş, G. T., & Bozkurt, İ. (2021). COVID-19 Hastalığı Tanı ve Tedavisinde Kullanılan Laboratuvar Testleri. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 8(2), 380-387.
  • Kritas, S. K., Ronconi, G., Caraffa, A., Gallenga, C. E., Ross, R., & Conti, P. (2020). Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents, 34(1), 9-14. https://doi.org/10.23812/20-Editorial-Kritas
  • Lee, J. S., Seppanen, E., Patel, J., Rodero, M. P., & Khosrotehrani, K. (2016). ST2 receptor invalidation maintains wound inflammation, delays healing and increases fibrosis. Exp Dermatol, 25(1), 71-74. https://doi.org/10.1111/exd.12833
  • Lee, J. U., Chang, H. S., Lee, H. J., Jung, C. A., Bae, D. J., Song, H. J. … Park, C. S. (2017). Upregulation of interleukin-33 and thymic stromal lymphopoietin levels in the lungs of idiopathic pulmonary fibrosis. BMC Pulm Med, 17(1), 39. https://doi.org/10.1186/s12890-017-0380-z
  • Li, D., Guabiraba, R., Besnard, A. G., Komai-Koma, M., Jabir, M. S., Zhang, L. … Xu, D. (2014). IL-33 promotes ST2-dependent lung fibrosis by the induction of alternatively activated macrophages and innate lymphoid cells in mice. J Allergy Clin Immunol, 134(6), 1422-1432.e1411. https://doi.org/10.1016/j.jaci.2014.05.011
  • Li, G., & Fan, Y. (2020). Coronavirus infections and immune responses. 92(4), 424-432. https://doi.org/10.1002/jmv.25685
  • Liao, M., Liu, Y., Yuan, J., Wen, Y., Xu, G., Zhao, J. … Amit, I. (2020). Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nature Medicine, 26, 842-844. https://doi.org/10.1038/s41591-020-0901-9
  • Liew, F. Y., Girard, J. P., & Turnquist, H. R. (2016). Interleukin-33 in health and disease. Nat Rev Immunol, 16(11), 676-689. https://doi.org/10.1038/nri.2016.95
  • Liew, F. Y., Pitman, N. I., & McInnes, I. B. (2010). Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol, 10(2), 103-110. https://doi.org/10.1038/nri2692
  • Lippi, G., Plebani, M., & Henry, B. M. (2020). Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta, 506, 145-148. https://doi.org/10.1016/j.cca.2020.03.022
  • Luzina, I. G., Kopach, P., Lockatell, V., Kang, P. H., Nagarsekar, A., Burke, A. P. … Atamas, S. P. (2013). Interleukin-33 potentiates bleomycin-induced lung injury. Am J Respir Cell Mol Biol, 49(6), 999-1008. https://doi.org/10.1165/rcmb.2013-0093OC
  • Manetti, M., Ibba-Manneschi, L., Liakouli, V., Guiducci, S., Milia, A. F., Benelli, G. … Cipriani, P. (2010). The IL1-like cytokine IL33 and its receptor ST2 are abnormally expressed in the affected skin and visceral organs of patients with systemic sclerosis. Ann Rheum Dis, 69(3), 598-605. https://doi.org/10.1136/ard.2009.119321
  • Marvie, P., Lisbonne, M., L'Helgoualc'h, A., Rauch, M., Turlin, B., Preisser, L. … Samson, M. (2010). Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J Cell Mol Med, 14(6b), 1726-1739. https://doi.org/10.1111/j.1582-4934.2009.00801.x
  • Matta, B. M., Lott, J. M., Mathews, L. R., Liu, Q., Rosborough, B. R., Blazar, B. R. … Turnquist, H. R. (2014). IL-33 is an unconventional Alarmin that stimulates IL-2 secretion by dendritic cells to selectively expand IL-33R/ST2+ regulatory T cells. J Immunol, 193(8), 4010-4020. https://doi.org/10.4049/jimmunol.1400481
  • Miller, A. M., Asquith, D. L., Hueber, A. J., Anderson, L. A., Holmes, W. M., McKenzie, A. N. … Liew, F. Y. (2010). Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res, 107(5), 650-658. https://doi.org/10.1161/circresaha.110.218867
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There are 46 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Articles
Authors

Çiğdem Damla Deniz 0000-0002-6052-4645

Fatih Yücel 0000-0002-1947-5853

Hasan Şenay 0000-0001-9956-1788

Fatma Kacar 0000-0001-7013-6403

Mehmet Sinan İyisoy 0000-0001-5895-9984

Nahide Baran 0000-0001-6387-423X

Betül Kozanhan 0000-0002-5097-9291

Mehmet Eryılmaz 0000-0002-5280-3943

Mehmet Koc 0000-0002-1433-8403

Project Number 39-04 sayı
Publication Date June 19, 2023
Published in Issue Year 2023 Volume: 6 Issue: 1

Cite

APA Deniz, Ç. D., Yücel, F., Şenay, H., Kacar, F., et al. (2023). Ağır COVID-19 Hastalarında Serum IL-33 Düzeylerinin Pulmoner Fibrozis ile İlişkisinin Değerlendirilmesi. Dünya Sağlık Ve Tabiat Bilimleri Dergisi, 6(1), 1-13.