Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?

Afşin, Dursun Erol; Laloğlu, Esra

doi:10.5578/flora.20239907

Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?

Dursun AFŞİN, (Erzurum Bölge Eğitim Araştırma Hastanesi, Göğüs Hastalıkları Kliniği, Erzurum, Türkiye)

Esra LALOĞLU (Atatürk Üniversitesi, Biyokimya Anabilim Dalı, Erzurum, Türkiye)

Flora İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Dergisi

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Yıl: 2023 Cilt: 28 Sayı: 1 Sayfa Aralığı: 77 - 86 Metin Dili: İngilizce DOI: 10.5578/flora.20239907 İndeks Tarihi: 02-05-2023

Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?

Öz:

Introduction: Failure to maintain the inflammatory and anti-inflammatory balance during COVID-19 treatment may result in a severe clinical course. In our study, we aimed to determine the relationship between the meteorin-like protein (metrnl), which plays a role in the anti-inflammatory balance, and the clinical course. Materials and Methods: Between October 2021 and December 2021, 160 patients who were hospitalized in our hospital and whose delta variant COVID-19 infection was confirmed and 80 healthy controls, were enrolled in the study. Patients were divided into two groups according to the severity degree of COVID-19 (Group 1: Moderate COVID-19, Group 2: Severe COVID-19 MAS). Results: When comparing the metrnl levels of the groups, it was observed that the metrnl level was statistically significantly lower in Group 2 patients (p< 0.001). While no statistically significant difference was observed between the healthy control group and Group 1, it was observed that the metrnl level of Group 2 patients was statistically significantly lower than the healthy control group (p= 0.77, <0.001 respectively). In the ROC curve analysis of Metrnl level performed in Group 1 and 2 patients, the cut-off value was taken as 17.54 ng/mL, its sensitivity was observed as 80% and the specificity was observed as 60% in predicting the development of severe COVID-19 in patients whose levels were below this value. Conclusion: The low level of metrnl, which is thought to play a key role in anti-inflammatory balance, contributes to the development of macrophage activation syndrome, which leads to the severe clinical course in COVID-19 patients.

Anahtar Kelime:

Metrnl, COVID-19 Hastalarında Makrofaj Aktivasyon Sendromunun Gelişimini Tahmin Etmek için Yeni Bir Biyobelirteç Olabilir mi?

Öz:

Giriş: COVID-19 seyrinde inflamatuvar ve anti-inflamatuar dengenin sağlanamaması hastalığın ağır klinik seyir göstermesine neden olabilmektedir. Çalışmamızda anti-inflamatuvar dengede rol oynayan meteorin-like protein (metrnl) ve klinik seyir arasındaki ilişkiyi tespit etmeyi amaçladık. Materyal ve Metod: Ekim 2021 ve Aralık 2021 tarihleri arasında hastanemize yatmış olan; gerçek zamanlı PCR yöntemiyle delta varyant COVID-19 tespit edilmiş 160 hasta ve 80 sağlıklı kontrol grubu çalışmaya dahil edildi. Hastalar COVID-19 ağırlık derecesine göre iki gruba ayrıldılar (Grup 1: Moderate (Orta Şiddetli) COVID-19, Grup 2: Severe (Ağır) COVID-19 MAS). Bulgular: Grupların metrnl düzeylerinin karşılaştırılmasında, Grup 2’deki hastaların metrnl düzeyinin istatistiksel olarak anlamlı düzeyde düşük olduğu görüldü (p< 0.001). Sağlıklı kontrol grubu (25.6 ± 5.7 ng/mL) ile Grup 1 arasında istatistiksel olarak anlamlı fark gözlenmezken Grup 2’deki hastaların metrnl düzeyinin sağlıklı kontrol grubuna göre istatistiksel olarak anlamlı düzeyde düşük olduğu gözlendi (sırasıyla p= 0.77, <0.001). Metrnl düzeyinin Grup 1 ve 2’deki hastalarda yapılan ROC curve analizinde eğri altında kalan alan (AUC) 0.754, cut-off değer olarak 17.64 ng/mL alındığında bu değerin altındaki hastalarda ağır COVID-19 gelişme durumunu tahmin etmede duyarlılığı %80, özgüllüğü ise %63 olarak bulundu. Sonuç: Anti-inflamatuvar dengede önemli bir rol oynadığı düşünülen metrnlin COVID-19 hastalarında düşük düzeyde olması, ağır klinik seyirde önemli rol oynayan makrofaj aktivasyon sendromu gelişiminde önemli paya sahiptir. COVID-19 hastalarında başlangıç döneminde tespit edilen düşük metrnl düzeyi, erken anti-inflamatuvar tedavi için yol gösterici olabilir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Kerget B, Çelik E, Kerget F, Aksakal A, Uçar EY, Araz Ö, et al. Evaluation of 3 month follow-up of patients with post-acute COVID-19 syndrome. J Med Virol 2022;94:2026-34. https://doi.org/10.1002/jmv.27579
2. Köktürk N, Babayiğit C, Kul S, Çetinkaya PD, Naycı SA, Barış SA, et al. The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients. Respir Med 2021;183:106433. https://doi.org/10.1016/j. rmed.2021.106433
3. Otsuka R, Seino KI. Macrophage activation syndrome and COVID-19. Inflamm Regen 2020;40:1-6. https://doi. org/10.1186/s41232-020-00131-w
4. Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: Pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol 2020;39:2085-94. https://doi.org/10.1007/ s10067-020-05190-5
5. Annane D. Corticosteroids for COVID-19. J Intensive Med 2021;1:14-25. https://doi.org/10.1016/j.jointm. 2021.01.002
6. Corral-Gudino L, Bahamonde A, Arnaiz-Revillas F, Gómez- Barquero J, Abadía-Otero J, García-Ibarbia C, et al. Methylprednisolone in adults hospitalized with COVID-19 pneumonia. Wien Klin Wochenschr 2021;133:303-11. https:// doi.org/10.1007/s00508-020-01805-8
7. Chaudhuri D, Sasaki K, Karkar A, Sharif S, Lewis K, Mammen MJ, et al. Corticosteroids in COVID-19 and non-COVID-19 ARDS: A systematic review and meta-analysis. Intensive Care Med 2021;47:521-37. https://doi.org/10.1007/ s00134-021-06394-2
8. Zheng Sl, Li ZY, Song J, Liu JM, Miao CY. Metrnl: A secreted protein with new emerging functions. Acta Pharmacol Sin 2016;37:571-9. https://doi.org/10.1038/aps.2016.9
9. Wang K, Li F, Wang C, Deng Y, Cao Z, Cui Y, et al. Serum levels of meteorin-like (metrnl) are increased in patients with newly diagnosed type 2 diabetes mellitus and are associated with insulin resistance. Med Sci Monit 2019;25:2337- 43. https://doi.org/10.12659/MSM.915331
10. Miao ZW, Hu WJ, Li ZZ, Miao CY. Involvement of the secreted protein metrnl in human diseases. Acta Pharmacol Sin 2020;41:1525-30. https://doi.org/10.1038/s41401- 020-00529-9
11. T.C. Sağlık Bakanlığı. Available from: https://covid19.saglik. gov.tr/Eklenti/43095/0/covid-19rehberieriskinhastayonetimivetedavi- 12042022pdf.pdf (Erişim tarihi: 12.04.2022).
12. Akçay MŞ, Özlü T, Yılmaz A. Radiological approaches to COVID-19 pneumonia. Turk J Med Sci 2020;50:604-10. https://doi.org/10.3906/sag-2004-160
13. Sjoding MW, Hofer TP, Co I, Courey A, Cooke CR, Iwashyna TJ. Interobserver reliability of the Berlin ARDS definition and strategies to improve the reliability of ARDS diagnosis. Chest 2018;153:361-7. https://doi.org/10.1016/j. chest.2017.11.037
14. Brodeur A, Gray D, Islam A, Bhuiyan S. A literature review of the economics of COVID-19. J Econ Surv 2021;35:1007- 44. https://doi.org/10.1111/joes.12423
15. Yamasaki K, Eeden SFV. Lung macrophage phenotypes and functional responses: Role in the pathogenesis of COPD. Int J of Mol Sci 2018;19:582. https://doi.org/10.3390/ ijms19020582
16. Kopf M, Schneider C, Nobs SP. The development and function of lung-resident macrophages and dendritic cells. Nat Immunol 2015;16:36-44. https://doi.org/10.1038/ ni.3052
17. Binger KJ, Gebhardt M, Heinig M, Rintisch C, Schroeder A, Neuhofer W, et al. High salt reduces the activation of IL-4-and IL-13-stimulated macrophages. J Clin Invest 2015;125:4223-38. https://doi.org/10.1172/JCI80919
18. Ushach I, Arrevillaga-Boni G, Heller GN, Pone E, Hernandez- Ruiz M, Catalan-Dibene J, et al. Meteorin-like/Meteorin- β is a novel immunoregulatory cytokine associated with inflammation. J Immunol 2018;201:3669-76. https://doi. org/10.4049/jimmunol.1800435
19. Kerget B, Afşin DE, Kerget F, Aşkın S, Akgün M. Is metrnl an adipokine involved in the anti-inflammatory response to acute exacerbations of COPD? Lung 2020;198:307-14. https://doi.org/10.1007/s00408-020-00327-4

APA	Afşin D, Laloğlu E (2023). Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?. , 77 - 86. 10.5578/flora.20239907
Chicago	Afşin Dursun Erol,Laloğlu Esra Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?. (2023): 77 - 86. 10.5578/flora.20239907
MLA	Afşin Dursun Erol,Laloğlu Esra Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?. , 2023, ss.77 - 86. 10.5578/flora.20239907
AMA	Afşin D,Laloğlu E Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?. . 2023; 77 - 86. 10.5578/flora.20239907
Vancouver	Afşin D,Laloğlu E Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?. . 2023; 77 - 86. 10.5578/flora.20239907
IEEE	Afşin D,Laloğlu E "Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?." , ss.77 - 86, 2023. 10.5578/flora.20239907
ISNAD	Afşin, Dursun Erol - Laloğlu, Esra. "Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?". (2023), 77-86. https://doi.org/10.5578/flora.20239907

APA	Afşin D, Laloğlu E (2023). Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?. Flora İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Dergisi, 28(1), 77 - 86. 10.5578/flora.20239907
Chicago	Afşin Dursun Erol,Laloğlu Esra Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?. Flora İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Dergisi 28, no.1 (2023): 77 - 86. 10.5578/flora.20239907
MLA	Afşin Dursun Erol,Laloğlu Esra Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?. Flora İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Dergisi, vol.28, no.1, 2023, ss.77 - 86. 10.5578/flora.20239907
AMA	Afşin D,Laloğlu E Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?. Flora İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Dergisi. 2023; 28(1): 77 - 86. 10.5578/flora.20239907
Vancouver	Afşin D,Laloğlu E Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?. Flora İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Dergisi. 2023; 28(1): 77 - 86. 10.5578/flora.20239907
IEEE	Afşin D,Laloğlu E "Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?." Flora İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Dergisi, 28, ss.77 - 86, 2023. 10.5578/flora.20239907
ISNAD	Afşin, Dursun Erol - Laloğlu, Esra. "Could Metrnl be a New Biomarker to Predict the Development of Macrophage Activation Syndrome in COVID-19 Patients?". Flora İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Dergisi 28/1 (2023), 77-86. https://doi.org/10.5578/flora.20239907