İnterferon-gamma ile İndüklenebilir Protein-10: COVID-19 Hastalığı için Bir Ölüm Göstergesi Değildir

Yıl 2023, , 363 - 368, 06.09.2023

Mahmud İslam , Hamad Dheir , Elif Özözen Şahin , Selcuk Yaylacı , Abdülkadir Aydın , Musa Pınar , Ertuğrul Güçlü , Ahmed Cihad Genç , Mehmet Köroğlu , Oğuz Karabay

https://doi.org/10.26453/otjhs.1276809

Öz

Amaç: Makrofajlardan salınan interferon-gama indüklenebilir protein-10 (IP-10) tromboz ile ilişkilidir. Bu çalışma, şiddetli COVID-19 nedeniyle takip edilen hastaların biyokimyasal belirteçlerini ve IP-10'un mortaliteyi göstermedeki rolünü araştırmayı amaçladı.
Materyal ve Metot: Bu çalışmada üniversite hastanesinin yoğun bakım ünitesinde (YBÜ) takip edilen 88 (Kadın %44,3) ağır hastanın retrospektif verileri değerlendirildi. Demografik ve laboratuvar verileri ile D-dimer, Ferritin, Ürik asit, IP-10 değerleri ve diğer biyokimyasal belirteçlere ilişkin veriler ölen ve yaşayan hastaların dosyalarından elde edildi.
Bulgular: Yoğun bakımda takip edilen COVID-19 enfeksiyonlu 88 hastanın yaş ortalaması 70,5 ±10 idi. Hayatta kalan gurupta, lenfosit sayısı 1,3 (1-2,1) K/uL, ferritin 151 (90,7-255), D-dimer 386 (293,5-650), LDH 220 (185-286) iken, ölen hastalarda ise, lenfosit sayısı 0,8 (0,5-1,1), ferritin 624 (296-1254) mcg/L, D-dimer 1280 (871-2245) ug/L, LDH 429.5 (368-560) U/L saptandı. Bu parametrelerde p değeri <0,05 idi. Buna karşılık, hayatta kalmayanlarda serum IP-10 seviyeleri hayatta kalanlar da 21,3 (1,2-31,6) pg/mL iken ölen hastalarda 26,6 (11,4-43,6) pg/mL, p=0,04.
Sonuç: Şiddetli COVID-19 hastalarında hayatta kalmayanlar ve hayatta kalanların karşılaştırıldığı bu çalışmada, ferritin, ve D-dimerin mortalite için iyi bir tahmin edici potansiyeli olduğu, IP-10'un ise bir belirleyici olamayacağı bulundu.

Anahtar Kelimeler

Biyobelirteç, COVID-19, IP-10, mortalite

Proje Numarası

BAPK 2021-9-33-83

Interferon-Gamma Inducible Protein-10: Not a Mortality Marker for COVID-19 Disease

Öz

Objective: Interferon-gamma inducible protein-10 (IP-10) released from macrophages is associated with thrombosis. We aimed to investigate patients' biochemical markers following severe COVID-19, concentrating on the role of IP-10 in mortality.
Materials and Methods: In our study, we retrospectively evaluated data from 88 (females, 44.3%) severe patients followed in our university hospital's intensive care unit (ICU). We obtained demographic and laboratory data from our study population's files and electronic records, including D-dimer, ferritin, uric acid, IP-10 values, and other biochemical markers.
Results: The mean age of all 88 patients with COVID-19 infection followed in the ICU was 70.5 ±10 years. The median for lymphocyte count was 1.3 (1-2.1) vs 0.8 (0.5-1.1) K/uL, ferritin 151 (90.7-255) vs 624 (296-1254) mcg/L, D-dimer 386 (293.5-650) vs 1280 (871-2245) ug/L, LDH 220 (185-286) vs 429.5 (368-560) U/L with a p-value of <0.05 in survivors vs non-survivors respectively. On the other hand, the level of IP-10 was 21.3 (13.2-31.6) vs 26.6 (11.4-43.6) pg/mL with a p-value of 0.04.
Conclusions: In this study, in which non-survivors and survivors were compared in severe COVID-19 patients, it was found that ferritin and D-dimer were good predictors of mortality, while IP-10 could not be a predictor of mortality.

Anahtar Kelimeler

Biomarker, COVID-19, IP-10, mortality

Destekleyen Kurum

Sakarya University of Scientific Research Projects Unit

Proje Numarası

BAPK 2021-9-33-83

Teşekkür

We want to thank the Sakarya University of Scientific Research Projects Unit (Research Project number: BAPK 2021-9-33-83) for their financial support. Also, we would like to thank the company HUMANİS for their contribution and nonconditional support.

Kaynakça

• Chen Y, Wang J, Liu C, Su L, Zhang D, Fan J, et al. IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19. Mol Med. 2020;26(1):97. doi:10.1186/s10020-020-00230-x
• Clinical spectrum. COVID-19 Treatment Guidelines. https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/. Accessed May 19, 2023.
• Corominas H, Castellví I, Pomar V, Antonijoan R, Mur I, Matas L, et al. Effectiveness and safety of intravenous tocilizumab to treat COVID-19-associated hyperinflammatory syndrome: Covizumab-6 observational cohort. Clin Immunol. 2021;223:108631. doi:10.1016/j.clim.2020.108631
• Buszko M, Park JH, Verthelyi D, Sen R, Young HA, Rosenberg AS. The dynamic changes in cytokine responses in COVID-19: a snapshot of the current state of knowledge. Nat Immunol. 2020;21(10):1146-1151. doi:10.1038/s41590-020-0779-1
• Schultze JL, Aschenbrenner AC. COVID-19 and the human innate immune system. Cell. 2021;184(7):1671-1692. doi:10.1016/j.cell.2021.02.029
• Bignon E, Miclot T, Terenzi A, Barone G, Monari A. Structure of the 5’ untranslated region in SARS-CoV-2 genome and its specific recognition by innate immune system via the human oligoadenylate synthase 1. Chem Commun . 2022;58(13):2176-2179. doi:10.1039/d1cc07006a
• Lu Q, Zhu Z, Tan C, Zhou H, Hu Y, Shen G, et al. Changes of serum IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10 and IL-4 in COVID-19 patients. Int J Clin Pract. 2021;75(9):e14462. doi:10.1111/ijcp.14462
• Sriram K, Insel PA. Inflammation and thrombosis in COVID-19 pathophysiology: proteinase-activated and purinergic receptors as drivers and candidate therapeutic targets. Physiol Rev. 2021;101(2):545-567. doi:10.1152/physrev.00035.2020
• Lev S, Gottesman T, Sahaf Levin G, Lederfein D, Berkov E, Diker D, et al. Observational cohort study of IP-10’s potential as a biomarker to aid in inflammation regulation within a clinical decision support protocol for patients with severe COVID-19. PLoS One. 2021;16(1):e0245296. doi:10.1371/journal.pone.0245296
• M Hussein A, Taha ZB, Gailan Malek A, Akram Rasul K, Hazim Kasim D, Jalal Ahmed R, et al. D-Dimer and Serum ferritin as an Independent Risk Factor for Severity in COVID-19 Patients. Mater Today Proc. Published online April 13, 2021. doi:10.1016/j.matpr.2021.04.009
• Xie H, Zhao J, Lian N, Lin S, Xie Q, Zhuo H. Clinical characteristics of non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: A retrospective study. Liver Int. 2020;40(6):1321-1326. doi:10.1111/liv.14449
• Buszko M, Nita-Lazar A, Park JH, Schwartzberg PL, Verthelyi D, Young HA, et al. Lessons learned: new insights on the role of cytokines in COVID-19. Nat Immunol. 2021;22(4):404-411. doi:10.1038/s41590-021-00901-9
• Liu M, Guo S, Stiles JK. The emerging role of CXCL10 in cancer (Review). Oncol Lett. 2011;2(4):583-589. doi:10.3892/ol.2011.300
• Yang Y, Shen C, Li J, Yuan J, Wei J, Huang F, et al. Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. J Allergy Clin Immunol. 2020;146(1):119-127.e4. doi:10.1016/j.jaci.2020.04.027
• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. doi:10.1016/S0140-6736(20)30183-5
• Rizzi M, Costanzo M, Tonello S, Matino E, Casciaro FG, Croce A, et al. Prognostic Markers in Hospitalized COVID-19 Patients: The Role of IP-10 and C-Reactive Protein. Dis Markers. 2022;2022:3528312. doi:10.1155/2022/3528312
• Mulla S, Molla MMA, Ahmed SMA, Akhtaruzzaman AKM, Saleh AA, Anwar S. Association of interferon gamma inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1 alpha, interleukin-6, and rs12252 single nucleotide polymorphism of interferon-induced transmembrane protein-3 gene with the severity of COVID-19 infection. Egypt J Intern Med. 2022;34(1):53. doi:10.1186/s43162-022-00141-9