The relationship of Eosinophil / Lymphocyte and D-Dimer / Fibrinogen ratios with the course of the disease in Covid-19 Patients

Abstract

Objective: Knowing the parameters that will measure the course and follow-up of the disease in the Covid-19 pandemic, which causes an important health problem all over the world, will make an important contribution to the understanding and management of the pathophysiology of the disease. The ratio of eosinophils, which are one of the peripheral blood cells responsible for the response to parasites and allergens, to lymphocyte (ELO), appears to be a biomarker for inflammatory conditions. Similarly, it is known that D-dimer/Fibrinogen ratio (DFO) is important to determine the severity of the disease in diseases with thromboembolic events. The aim of this study was to evaluate the relationship of ELO and DFO with the course of the disease in Covid-19 patients, where inflammation and thromboembolic events are at the forefront. Method: The study was conducted as a retrospective data search. The research population included patients hospitalized for Covid-19 pneumonia between April and December 2020. The patients were divided into groups as those who recovered and were discharged within 14 days, and those who required hospitalization for more than 14 days or died. Age, gender and comorbidities of the patients, as well as laboratory values at the time of hospitalization were analyzed. Results: A total of 486 patients were included in the study. Advanced age, presence of additional disease, high CRP, Ferritin, LDH and leukocyte count, and low lymphocyte count were found to be associated with poor prognosis in the 14-day course of the disease, while ELO value was not significant. While D-dimer and fibrinogen values were not different between the patients who recovered and did not heal in the 14-day period, DFO was found to be significantly higher in both the non-healed and ex-groups. The sensitivity of DFO in determining prolonged hospitalization was 66%, its specificity was 68%, and its sensitivity was 73%, and its specificity was 67% in determining mortality. Conclusion: While ELO was not significant in the 14-day course of patients hospitalized with Covid-19 pneumonia, DFO elevation was found to be significant in showing both prolonged hospitalization and 14-day mortality.

Keywords

• COVID-19
• Eosinophil
• Lymphocyte
• Eosinophil/Lymphocyte ratio
• D-dimer/Fibrinogen ratio

Covid-19 hastalarında Eozinofil / Lenfosit ve D-Dimer/ Fibrinojen oranlarının hastalık seyri ile ilişkisi

Abstract

Amaç: Tüm dünyada önemli sağlık sorununa neden olan Covid-19 pandemisinde, hastalığın seyrini ve takibini ölçecek parametrelerin bilinmesi, hastalığın patofizyolojisinin anlaşılmasına ve yönetimine önemli katkı sağlayacaktır. Parazit ve allerjenlere karşı gelişen yanıttan sorumlu periferik kan hücrelerinden olan eozinofillerin, lenfosit ile olan oranı (ELO) inflamatuar durumlar için bir biyolojik belirteç olarak görülmektedir. Benzer şekilde tromboembolik olaylarla seyreden hastalıklarda D-dimer/ Fibrinojen oranının (DFO) hastalığın ağırlığını belirlemede önemli olduğu bilinmektedir. Bu araştırmada amaç inflamasyon ve tromboembolik olayların ön planda olduğu Covid-19 hastalarında ELO ve DFO’nun hastalığın seyri ile ilişkisini değerlendirmektir. Yöntem: Araştırma retrospektif veri taraması olarak yapıldı. Araştırma popülasyonu, Covid-19 pnömonisi nedeniyle Nisan – Aralık 2020 tarihleri arasında hastaneye yatırılan hastaları içermekteydi. Hastalar 14 gün içinde iyileşerek taburcu olanlar ve 14 günden uzun süre yatışı gereken veya ölenler olarak gruplara ayrıldı. Hastaların yaş, cinsiyet ve ek hastalıkları yanısıra hastaneye yatış anındaki laboratuvar değerleri analiz edildi. Bulgular: Toplam 486 hasta incelemeye alındı. İncelenen laboratuvar parametrelerinden ileri yaş, ek hastalık varlığı, CRP, Ferritin, LDH ve lökosit sayısı yüksekliği ve lenfosit sayısı düşüklüğü hastalığın 14 günlük seyrinde kötü prognoz ile ilişkili bulunurken ELO değerinde böyle bir anlamlılık bulunmadı. D-dimer ve fibrinojen değerleri, 14 günlük süreçte, iyileşen ve iyileşmeyen hastalar arasında farklı bulunmazken DFO hem iyileşmeyen grupta hem de ölen grupta anlamlı olarak yüksek bulundu. DFO’nun uzamış hastane yatışını belirlemede duyarlılığı %66 özgüllüğü %68, mortaliteyi belirlemede ise duyarlılığı %73, özgüllüğü %67 olarak hesaplandı. Sonuç: Covid-19 pnömonisi ile hastaneye yatan hastaların 14 günlük seyrinde ELO anlamlı bulunmazken DFO yüksekliği hem uzamış hastane yatışı hem de 14 günlük mortaliteyi göstermede anlamlı bulundu.

Keywords

• Covid-19
• Eozinofil
• Lenfosit
• Eozinofil/Lenfosit oranı
• D-dimer/Fibrinojen oranı

References

1. 1. LiuJ, LiuY, XiangP, PuL, XiongH, LiC, ZhangM, TanJ, Xu Y, Song R, Song M, Wang L, Zhang W, Han B, Yang L, Wang X, Zhou G, Zhang T, Li B, Wang Y, Chen Z and Wang X: Neutrophil- to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J Transl Med 18(1):206, 2020. PMID: 32434518. DOI: 10.1186/s12967-020-02374-0
2. 2. Chang MC, Park YK, Kim BO and Park D: Risk factors for disease progression in COVID-19 patients. BMC Infect Dis 2020;20(1):445,. PMID: 32576139. DOI: 10.1186/s12879-020- 05144-x
3. 3. Uhm TG, Kim BS and Chung IY: Eosinophil development, regulation of eosinophil-specific genes, and role of eosinophils in the pathogenesis of asthma. Allergy Asthma Immunol Res 2012;4(2):68-79,. PMID: 22379601. DOI: 10.4168/aair. 2012.4.2.68
4. 4. Flores-Torres AS, Salinas-Carmona MC, Salinas E and Rosas-Taraco AG: Eosinophils and respiratory viruses. Viral Immunol 2019;32(5):198-207,. PMID: 31140942. DOI: 10.1089/vim.2018.0150
5. 5. Phipps S, Lam CE, Mahalingam S, Newhouse M, Ramirez R, Rosenberg HF, Foster PS and Matthaei KI: Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. Blood 2007;110(5):1578-1586,. PMID: 17495130. DOI: 10.1182/blood-2007-01-071340
6. 6. Samarasinghe AE, Melo RC, Duan S, LeMessurier KS, Liedmann S, Surman SL, Lee JJ, Hurwitz JL, Thomas PG and McCullers JA: Eosinophils promote antiviral immunity in mice infected with influenza A virus. J Immunol 2017;198(8):3214-3226,. PMID: 28283567. DOI:0.4049/jimmunol.1600787
7. 7. XieG, DingF, HanL, YinD, Lu Hand Zhang M: The role of peripheral blood eosinophil counts in COVID-19 patients. Allergy, 2020. PMID: 32562554. DOI: 10.1111/all.14465
8. 8. Vasiliki E., Kopoulou G., Garmpıs N., Damaskos C., Valsami S., Dimitroulis D. et al. The Impact of Peripheral Eosinophil Counts and Eosinophil to Lymphocyte Ratio (ELR) in the Clinical Course of COVID-19 Patients: A Retrospective Study. In Vivo 2021;35:641-648 doi:10.21873/invivo.12303.

9. 9. Tanni F, Akker E, Zaman MM, Figueroa N, Tharian B and Hupart KH: Eosinopenia and COVID-19. J Am Osteopath Assoc, 2020. PMID: 32672799. DOI: 10.7556/jaoa.2020.091
10. 10. Lu G and Wang J: Dynamic changes in routine blood parameters of a severe COVID-19 case. Clin Chim Acta 2020;508: 98-102. PMID: 32405079. DOI: 10.1016/j.cca.2020.04.034
11. 11. Çekici Y, Yılmaz M and Seçen Ö: New inflammatory indicators: Association of high eosinophil-to-lymphocyte ratio and low lymphocyte-to-monocyte ratio with smoking. J Int Med Res 2019;47(9): 4292-4303. PMID: 31319727. DOI: 10.1177/ 0300060519862077
12. 12. Branicka O, Rogala B and Glück J: Eosinophil/neutrophil/ platelet-to-lymphocyte ratios in various types of immediate hypersensitivity to NSAIDs: A preliminary study. Int Arch Allergy Immunol 2020;181(10): 774-782. PMID: 32814336. DOI: 10.1159/000509116
13. 13. Küçükceran K., Ayranci M. K., Girişgin A. S., Koçak S. Predictive value of D-dimer/albumin ratio and fibrinogen/ albumin ratio for in-hospital mortality in patients with COVID-19. Int J Clin Pract. 2021;00:e14263. doi: 10.1111/ijcp.14263 .
14. 14. Bai, Y., Zheng, Y.-Y., Tang, J.-N., Yang, X.-M., Guo, Q.-Q., Zhang, J.-C., et al. D-Dimer to Fibrinogen Ratio as a Novel Prognostic Marker in Patients After Undergoing Percutaneous Coronary Intervention: A Retrospective Cohort Study. Clin App Thromb Hemost., 2020;26, 107602962094858. doi:10.1177/1076029620948586
15. 15. Lippi, G, Cervellin, G, Franchini, M, et al. Biochemical markers for the diagnosis of venous thromboembolism: the past, present and future. J Thromb Thrombolysis. 2010;30(4):459–471.
16. 16. Heim, SW, Schectman, JM, Siadaty, MS, et al. D-dimer testing for deep venous thrombosis: a metaanalysis. Clin Chem. 2004;50(7):1136–1147.
17. 17. Arbustini, E, Narula, N, D’Armini, AM. Fibrinogen: a circulating factor in search of its genetic architecture. Circulation. 2013;128(12):1276–1280.
18. 18. Ang, L, Behnamfar, O, Palakodeti, S, et al. Elevated baseline serum fibrinogen: effect on 2-year major adverse cardiovascular events following percutaneous coronary intervention. J Am Heart Assoc. 2017;6(11):e006580.
19. 19. Osawa I, Okamoto K, Ikeda M, Otani A, Wakimoto Y, Yamashita M et al. Dynamic changes in fibrinogen and D-dimer levels in COVID-19 patients on nafamostat mesylate. J Thrombosis and Thrombolysis. 2021;51:649-656. Doi: 10.1007/s11239-020-02275-5.
20. 20. Al-Samkari H, Karp Leaf RS, Dzik WH, Carlson JCT, Fogerty AE, Waheed A et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood, 2020;136(4):489-500.
21. 21. Wright FL, Vogler TO, Moore EE, Moore HB, Wohlauer MV, Urban S et al. Fibrinolysis shutdown correlation with thromboembolic events in severe COVID-19 infection. J Am Coll Surg. 2020;231(2): 193-203.
22. 22. Klovaite J, Nordestgaard BG, Tybjaerg-Hansen A and Benn M. Elevated Fibrinogen Levels are associated with risk of Pulmonary Embolism, but not with Deep Venous Thrombosis. AM J Resp Crit Care Med. 2012;187(3): 286-293.
23. 23. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F et al. Pulmonary vascular endothelialitis, thrombosis and angiogenesis in Covid-19. N Engl J Med. 2020;383:120-128.