Neutrophil-to-lymphocyte and fibrinogen-to-albumin ratios may be indicators of worse outcomes in ICU patients with COVID-19

Abstract

Background/Aim: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a pandemic. Early diagnosis of complications and mortality caused by this disease will guide the treatment process in patients with COVID-19. We aimed to investigate whether the neutrophil/lymphocyte and fibrinogen/albumin ratios can predict mortality in COVID-19 patients. Methods: A total of 102 adult patients (≥18 years) who were followed up in the intensive care unit (ICU) between May and August 2020 because of COVID-19 were included in this retrospective cohort study. Demographic data, comorbid diseases, and hematological parameters of the patients during admission to the ICU were examined. Hematological parameters such as leukocyte, neutrophil, lymphocyte, platelet counts, C-reactive protein (CRP), D-dimer, and lactate data were recorded. The neutrophil-to-lymphocyte ratio (NLR) and fibrinogen-to-albumin ratio (FAR) were calculated, and their effects on mortality were examined. Results: Of the patients, 71 (69.6%) were male and the mean age of all patients was 69.1 (14.3) (24–103) years. Comorbid diseases of the patients were as follows: Hypertension (n=40, 39.2%), diabetes mellitus (n=28, 27.4%), chronic obstructive pulmonary disease (n=20, 19.6%), coronary artery disease (n=14, 13.7%), heart failure (n=4, 3.9%), and cerebrovascular disease (n=3, 2.9%). Mortality was higher in older patients (median age = 72; range = 62–80 years) (P=0.043), and bilateral infiltration was observed in lung computed tomography images of all patients who died. Mortality was higher in patients with NLR>9.16, FAR>0.15, D-dimer>2.01 mg/L, CRP >11.6 mg/dL, lactate >2.3 mmol/L. Conclusion: Elevated levels of neutrophil-to-lymphocyte Ratio, fibrinogen-to-albumin ratio, D-dimer, CRP, and lactate were associated with worse outcomes among COVID-19 patients in the ICU.

Keywords

• COVID-19
• Mortality
• Neutrophil-to-lymphocyte ratio

Kaynakça

1. 1. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G, et al. Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic. J Am Coll Cardiol. 2020 May 12;75(18):2352-71. doi: 10.1016/j.jacc.2020.03.031.
2. 2. Bangash MN, Patel J, Parekh D. COVID-19 and the liver: little cause for concern. Lancet Gastroenterol Hepatol. 2020 Jun;5(6):529-30. doi: 10.1016/S2468-1253(20)30084-4.
3. 3. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-4. doi: 10.1016/S0140-6736(20)30628-0.
4. 4. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-42. doi: 10.1001/jama.2020.2648.
5. 5. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-7. doi: 10.1111/jth.14768.
6. 6. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol. 2020 Jul 1;5(7):831-40. doi: 10.1001/jamacardio.2020.1286.
7. 7. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-20. doi: 10.1056/NEJMoa2002032.
8. 8. 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 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5.

9. 9. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):762-8. doi: 10.1093/cid/ciaa248.
10. 10. Sun DW, An L, Lv GY. Albumin-fibrinogen ratio and fibrinogen-prealbumin ratio as promising prognostic markers for cancers: an updated meta-analysis. World J Surg Oncol. 2020 Jan 13;18(1):9. doi: 10.1186/s12957-020-1786-2.
11. 11. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-9. doi: 10.1001/jama.2020.1585.
12. 12. Russell CD, Parajuli A, Gale HJ, Bulteel NS, Schuetz P, de Jager CPC, et al. The utility of peripheral blood leucocyte ratios as biomarkers in infectious diseases: A systematic review and meta-analysis. J Infect. 2019 May;78(5):339-48. doi: 10.1016/j.jinf.2019.02.006.
13. 13. Huguet E, Maccallini G, Pardini P, Hidalgo M, Obregon S, Botto F, et al. Reference Values for Neutrophil to Lymphocyte Ratio (NLR), a Biomarker of Cardiovascular Risk, According to Age and Sex in a Latin American Population. Curr Probl Cardiol. 2021 Mar;46(3):100422. doi: 10.1016/j.cpcardiol.2019.04.002.
14. 14. Park JS, Seo KW, Choi BJ, Choi SY, Yoon MH, Hwang GS, et al. Importance of prognostic value of neutrophil to lymphocyte ratio in patients with ST-elevation myocardial infarction. Medicine (Baltimore). 2018 Nov;97(48):e13471. doi: 10.1097/MD.0000000000013471.
15. 15. Mei Z, Shi L, Wang B, Yang J, Xiao Z, Du P, et al. Prognostic role of pretreatment blood neutrophil-to-lymphocyte ratio in advanced cancer survivors: A systematic review and meta-analysis of 66 cohort studies. Cancer Treat Rev. 2017 Jul;58:1-13. doi: 10.1016/j.ctrv.2017.05.005.
16. 16. Forget P, Khalifa C, Defour JP, Latinne D, Van Pel MC, De Kock M. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Res Notes. 2017 Jan 3;10(1):12. doi: 10.1186/s13104-016-2335-5.
17. 17. Fu J, Kong J, Wang W, Wu M, Yao L, Wang Z, et al. The clinical implication of dynamic neutrophil to lymphocyte ratio and D-dimer in COVID-19: A retrospective study in Suzhou China. Thromb Res. 2020 Aug;192:3-8. doi: 10.1016/j.thromres.2020.05.006.
18. 18. Liu Y, Du X, Chen J, Jin Y, Peng L, Wang HHX, et al. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect. 2020 Jul;81(1):e6-e12. doi: 10.1016/j.jinf.2020.04.002.
19. 19. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-43. doi: 10.1001/jamainternmed.2020.0994.
20. 20. Fan BE. Hematologic parameters in patients with COVID-19 infection: a reply. Am J Hematol. 2020 Aug;95(8):E215. doi: 10.1002/ajh.25847.
21. 21. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-81. doi: 10.1016/S2213-2600(20)30079-5.
22. 22. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020 Apr 28;323(16):1612-4. doi: 10.1001/jama.2020.4326.
23. 23. Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. Covid-19 in Critically Ill Patients in the Seattle Region - Case Series. N Engl J Med. 2020 May 21;382(21):2012-22. doi: 10.1056/NEJMoa2004500.
24. 24. Deng Y, Liu W, Liu K, Fang YY, Shang J, Zhou L, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. Chin Med J (Engl). 2020 Jun 5;133(11):1261-7. doi: 10.1097/CM9.0000000000000824.
25. 25. Tan L, Wang Q, Zhang D, Ding J, Huang Q, Tang YQ, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther. 2020 Mar 27;5(1):33. doi: 10.1038/s41392-020-0148-4. Erratum in: Signal Transduct Target Ther. 2020 Apr 29;5(1):61. doi: 10.1038/s41392-020-0148-4.
26. 26. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-13. doi: 10.1016/S0140-6736(20)30211-7.
27. 27. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020 Jul;506:145-8. doi: 10.1016/j.cca.2020.03.022.
28. 28. Yıldırım ÖT, Akşit E, Aydın F, Aydın AH, Dağtekin E. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio can be used as biomarkers for non-dipper blood pressure. J Surg Med. 2019;3(1):4-7. doi: 10.28982/josam.436951
29. 29. Forget P, Moreau N, Engel H, Cornu O, Boland B, De Kock M, et al. The neutrophil-to-lymphocyte ratio (NLR) after surgery for hip fracture (HF). Arch Gerontol Geriatr. 2015 Mar-Apr;60(2):366-71. doi: 10.1016/j.archger.2014.11.008.
30. 30. Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clin Infect Dis. 2020 Mar 16:ciaa270. doi: 10.1093/cid/ciaa270.
31. 31. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62. doi: 10.1016/S0140-6736(20)30566-3.
32. 32. Snijders D, Schoorl M, Schoorl M, Bartels PC, van der Werf TS, Boersma WG. D-dimer levels in assessing severity and clinical outcome in patients with community-acquired pneumonia. A secondary analysis of a randomised clinical trial. Eur J Intern Med. 2012 Jul;23(5):436-41. doi: 10.1016/j.ejim.2011.10.019.