Neutrophil-to-Lymphocyte Ratio Cut-Off Point for COVID-19 Mortality: A Retrospective Study
-
Zahedin Kheyri
,
Sepehr Metanat
,
Hadiseh Hosamirudsari
,
Samaneh Akbarpour
,
Maryam Shojaei
,
Neda Faraji
,
Fariba Mansouri
,
Fatemeh Taghizadeh
,
Fatemeh Ahmadian
Abstract
Several months have passed since the onset of the COVID-19 pandemic. Multiple characteristics have been proposed as prognostic factors so far. This study aims to provide evidence on the association of neutrophil-to-lymphocyte ratio (NLR) at the hospitalization time and three desired outcomes (mortality, prolonged hospitalization, and intensive care unit [ICU] admission). We designed a single-centre retrospective observational study in Baharloo Hospital (Tehran, Iran) from 20 February to 19 April 2020. Patients with confirmed COVID-19 diagnosis via rt-PCR or chest CT imaging were included. Demographic and clinical data were obtained. The sample was divided into three groups, using tertile boundaries of initial NLR. The differences in mortality, comorbidities, hospitalization duration, drug administration, and ICU admission between these three groups were investigated. The identified confounding factors were adjusted to calculate the odds ratio of death, ICU admission, and prolonged hospitalization. Nine hundred sixty-three patients were included. In total, 151 and 212 participants experienced mortality and ICU admission, respectively. In multivariate logistic regression models, the adjusted odds ratio for mortality event in the second and third tertile of initial NLR after full adjustment were 1.89 (95% CI:1.07-3.32) and 2.57 (95% CI:1.48-4.43) and for ICU admission were 1.85 (95% CI:1.14-3.01) and 2.88 (95% CI:1.79-4.61), respectively. The optimal cut-off value of the initial NLR for predicting mortality was 4.27. Initial NLR can predict mortality and ICU admission in COVID-19 patients. Further investigations for curating the calculated cut-off can propose initial NLR as an indicator of poor prognosis for COVID-19 patients.
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7. Xiurong D, Yanhua Y, Bichao L, Jianbo H, Ming C, Yanfang K, et al. Dynamic profile and clinical implications of hematological parameters in hospitalized patients with coronavirus disease 2019. Clin Chem Lab Med 2020;58:1365-71.
8. Ye W, Chen G, Li X, Lan X, Ji C, Hou M, et al. Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19. Respir Res 2020;21:169.
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13. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J Transl Med 2020;18:206.
14. 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;395:507-13.
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19. Verdoia M, Schaffer A, Barbieri L, Aimaretti G, Marino P, Sinigaglia F, et al. Impact of diabetes on neutrophil-to-lymphocyte ratio and its relationship to coronary artery disease. Diabetes Metab 2015;41:304-11.
20. Liu CC, Ko HJ, Liu WS, Hung CL, Hu KC, Yu LY, et al. Neutrophil-to-lymphocyte ratio as a predictive marker of metabolic syndrome. Medicine (Baltimore) 2019;98:e17537.
21. Zeb A, Khurshid S, Bano S, Rasheed U, Zammurrad S, Khan MS, et al. The Role of the Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Markers of Disease Activity in Ankylosing Spondylitis. Cureus 2019;11:e6025.
22. Palacios Huatuco RM, Pantoja Pachajoa DA, Bruera N, Pinsak AE, Llahi F, Doniquian AM, et al. Neutrophil-to-lymphocyte ratio as a predictor of complicated acute diverticulitis: A retrospective cohort study. Ann Med Surg (Lond) 2021;63:102128.
23. Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther 2013;11:55-9.
24. Education IsMoHaM. Flowchart for Diagnosis and Treatment of COVID 19 at Outpatient and Inpatient Service Levels 2020. (Accessed Oct 10, 2020 at http://medcare.behdasht.gov.ir/uploads/%D9%86%D8%B3%D8%AE%D9%87_%D8%B3%D9%88%D9%85_%D9%81%D9%84%D9%88%DA%86%D8%A7%D8%B1%D8%AA.pdf).
25. Kerboua KE. NLR: A Cost-effective Nomogram to Guide Therapeutic Interventions in COVID-19. Immunol Invest 2021;50:92-100.
26. Berhane M, Melku M, Amsalu A, Enawgaw B, Getaneh Z, Asrie F. The Role of Neutrophil to Lymphocyte Count Ratio in the Differential Diagnosis of Pulmonary Tuberculosis and Bacterial Community-Acquired Pneumonia: a Cross-Sectional Study at Ayder and Mekelle Hospitals, Ethiopia. Clin Lab 2019;65.
27. Liu H, Zhang H, Wan G, Sang Y, Chang Y, Wang X, et al. Neutrophil-lymphocyte ratio: a novel predictor for short-term prognosis in acute-on-chronic hepatitis B liver failure. J Viral Hepat 2014;21:499-507.
28. Chen XQ, Xue CR, Hou P, Lin BQ, Zhang JR. Lymphocyte-to-monocyte ratio effectively predicts survival outcome of patients with obstructive colorectal cancer. World J Gastroenterol 2019;25:4970-84.
29. Gezer NS, Bengi G, Baran A, Erkmen PE, Topalak ÖS, Altay C, et al. Comparison of radiological scoring systems, clinical scores, neutrophil-lymphocyte ratio and serum C-reactive protein level for severity and mortality in acute pancreatitis. Rev Assoc Med Bras (1992) 2020;66:762-70.
30. Wang P, Anderson N, Pan Y, Poon L, Charlton C, Zelyas N, et al. The SARS-CoV-2 Outbreak: Diagnosis, Infection Prevention, and Public Perception. Clin Chem 2020;hvaa080.
31. Ali P, Sina S, Ahmadreza B, Mohammad V, Laya Jalilian K, Mohammad Esmaeil A, et al. Neutrophil-to-lymphocyte ratio (NLR) greater than 6.5 may reflect the progression of COVID-19 towards an unfavorable clinical outcome. Iran J Microbiol 2020;12:466-74.
32. Eid MM, Al-Kaisy M, Latif Regeia WA, Jiwa Khan H. The Prognostic Accuracy of Neutrophil-Lymphocyte Ratio in COVID-19 Patients. Front emerg Med 2021;5:e8.
33. 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;323:1061-9.
34. Abassi Z, Assady S, Khoury EE, Heyman SN. Letter to the Editor: Angiotensin-converting enzyme 2: an ally or a Trojan horse? Implications to SARS-CoV-2-related cardiovascular complications. Am J Physiol Heart Circ Physiol 2020;318:H1080-3.
35. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med 2020;46:586-90.
36. 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;81:e6-e12.
37. 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;71:762-8.
38. Yang AP, Liu JP, Tao WQ, Li HM. The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. Int Immunopharmacol 2020;84:106504.
39. Zhang B, Zhou X, Qiu Y, Feng F, Feng J, Jia Y, et al. Clinical characteristics of 82 death cases with COVID-19. PLoS One 2020;15:e0235458.
40. Tatum D, Taghavi S, Houghton A, Stover J, Toraih E, Duchesne J. Neutrophil-to-Lymphocyte Ratio and Outcomes in Louisiana COVID-19 Patients. Shock 2020;54:652-8.
2. WHO. Coronavirus disease 2019 (COVID-19) situation report 2020. (Accessed Oct 16, 2020, at https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports.)
3. Song CY, Xu J, He JQ, Lu YQ. COVID-19 early warning score: a multi-parameter screening tool to identify highly suspected patients. medRxiv 2020.
4. Wu C, Chen X, Cai Y, Xia Ja, 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;180:934-43.
5. 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;395:497-506.
6. Lavezzo E, Franchin E, Ciavarella C, Cuomo-Dannenburg G, Barzon L, Del Vecchio C, et al. Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature 2020;584:425-9.
7. Xiurong D, Yanhua Y, Bichao L, Jianbo H, Ming C, Yanfang K, et al. Dynamic profile and clinical implications of hematological parameters in hospitalized patients with coronavirus disease 2019. Clin Chem Lab Med 2020;58:1365-71.
8. Ye W, Chen G, Li X, Lan X, Ji C, Hou M, et al. Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19. Respir Res 2020;21:169.
9. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. J Infect 2020;80:607-13.
10. Wan S, Yi Q, Fan S, Lv J, Zhang X, Guo L, et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). medRxiv 2020.
11. Martín-Rojas RM, Pérez-Rus G, Delgado-Pinos VE, Domingo-González A, Regalado-Artamendi I, Alba-Urdiales N, et al. COVID-19 coagulopathy: An in-depth analysis of the coagulation system. Eur J Haematol 2020;105:741-750.
12. Akbari H, Tabrizi R, Lankarani KB, Aria H, Vakili S, Asadian F, et al. The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. Life Sci 2020;258:118167.
13. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J Transl Med 2020;18:206.
14. 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;395:507-13.
15. Tanboğa IH, Canpolat U, Çetin EHÖ, Kundi H, Çelik O, Çağlayan M, et al. Development and validation of clinical prediction model to estimate the probability of death in hospitalized patients with COVID-19: Insights from a nationwide database. J Med Virol 2021;93:3015-22.
16. Shang W, Dong J, Ren Y, Tian M, Li W, Hu J, et al. The value of clinical parameters in predicting the severity of COVID-19. J Med Virol 2020:10.1002/jmv.26031.
17. Han Q, Wen X, Wang L, Han X, Shen Y, Cao J, et al. Role of hematological parameters in the diagnosis of influenza virus infection in patients with respiratory tract infection symptoms. J Clin Lab Anal 2020;34:e23191.
18. Cupp MA, Cariolou M, Tzoulaki I, Aune D, Evangelou E, Berlanga-Taylor AJ. Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies. BMC Med 2020;18:360.
19. Verdoia M, Schaffer A, Barbieri L, Aimaretti G, Marino P, Sinigaglia F, et al. Impact of diabetes on neutrophil-to-lymphocyte ratio and its relationship to coronary artery disease. Diabetes Metab 2015;41:304-11.
20. Liu CC, Ko HJ, Liu WS, Hung CL, Hu KC, Yu LY, et al. Neutrophil-to-lymphocyte ratio as a predictive marker of metabolic syndrome. Medicine (Baltimore) 2019;98:e17537.
21. Zeb A, Khurshid S, Bano S, Rasheed U, Zammurrad S, Khan MS, et al. The Role of the Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Markers of Disease Activity in Ankylosing Spondylitis. Cureus 2019;11:e6025.
22. Palacios Huatuco RM, Pantoja Pachajoa DA, Bruera N, Pinsak AE, Llahi F, Doniquian AM, et al. Neutrophil-to-lymphocyte ratio as a predictor of complicated acute diverticulitis: A retrospective cohort study. Ann Med Surg (Lond) 2021;63:102128.
23. Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther 2013;11:55-9.
24. Education IsMoHaM. Flowchart for Diagnosis and Treatment of COVID 19 at Outpatient and Inpatient Service Levels 2020. (Accessed Oct 10, 2020 at http://medcare.behdasht.gov.ir/uploads/%D9%86%D8%B3%D8%AE%D9%87_%D8%B3%D9%88%D9%85_%D9%81%D9%84%D9%88%DA%86%D8%A7%D8%B1%D8%AA.pdf).
25. Kerboua KE. NLR: A Cost-effective Nomogram to Guide Therapeutic Interventions in COVID-19. Immunol Invest 2021;50:92-100.
26. Berhane M, Melku M, Amsalu A, Enawgaw B, Getaneh Z, Asrie F. The Role of Neutrophil to Lymphocyte Count Ratio in the Differential Diagnosis of Pulmonary Tuberculosis and Bacterial Community-Acquired Pneumonia: a Cross-Sectional Study at Ayder and Mekelle Hospitals, Ethiopia. Clin Lab 2019;65.
27. Liu H, Zhang H, Wan G, Sang Y, Chang Y, Wang X, et al. Neutrophil-lymphocyte ratio: a novel predictor for short-term prognosis in acute-on-chronic hepatitis B liver failure. J Viral Hepat 2014;21:499-507.
28. Chen XQ, Xue CR, Hou P, Lin BQ, Zhang JR. Lymphocyte-to-monocyte ratio effectively predicts survival outcome of patients with obstructive colorectal cancer. World J Gastroenterol 2019;25:4970-84.
29. Gezer NS, Bengi G, Baran A, Erkmen PE, Topalak ÖS, Altay C, et al. Comparison of radiological scoring systems, clinical scores, neutrophil-lymphocyte ratio and serum C-reactive protein level for severity and mortality in acute pancreatitis. Rev Assoc Med Bras (1992) 2020;66:762-70.
30. Wang P, Anderson N, Pan Y, Poon L, Charlton C, Zelyas N, et al. The SARS-CoV-2 Outbreak: Diagnosis, Infection Prevention, and Public Perception. Clin Chem 2020;hvaa080.
31. Ali P, Sina S, Ahmadreza B, Mohammad V, Laya Jalilian K, Mohammad Esmaeil A, et al. Neutrophil-to-lymphocyte ratio (NLR) greater than 6.5 may reflect the progression of COVID-19 towards an unfavorable clinical outcome. Iran J Microbiol 2020;12:466-74.
32. Eid MM, Al-Kaisy M, Latif Regeia WA, Jiwa Khan H. The Prognostic Accuracy of Neutrophil-Lymphocyte Ratio in COVID-19 Patients. Front emerg Med 2021;5:e8.
33. 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;323:1061-9.
34. Abassi Z, Assady S, Khoury EE, Heyman SN. Letter to the Editor: Angiotensin-converting enzyme 2: an ally or a Trojan horse? Implications to SARS-CoV-2-related cardiovascular complications. Am J Physiol Heart Circ Physiol 2020;318:H1080-3.
35. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med 2020;46:586-90.
36. 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;81:e6-e12.
37. 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;71:762-8.
38. Yang AP, Liu JP, Tao WQ, Li HM. The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. Int Immunopharmacol 2020;84:106504.
39. Zhang B, Zhou X, Qiu Y, Feng F, Feng J, Jia Y, et al. Clinical characteristics of 82 death cases with COVID-19. PLoS One 2020;15:e0235458.
40. Tatum D, Taghavi S, Houghton A, Stover J, Toraih E, Duchesne J. Neutrophil-to-Lymphocyte Ratio and Outcomes in Louisiana COVID-19 Patients. Shock 2020;54:652-8.
| Files | ||
| Issue | Vol 60, No 1 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/acta.v60i1.8325 | |
| Keywords | ||
| Blood cell count Neutrophil-to-lymphocyte ratio Coronavirus disease 2019 (COVID-19) Mortality Intensive care units | ||
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How to Cite
1.
Kheyri Z, Metanat S, Hosamirudsari H, Akbarpour S, Shojaei M, Faraji N, Mansouri F, Taghizadeh F, Ahmadian F. Neutrophil-to-Lymphocyte Ratio Cut-Off Point for COVID-19 Mortality: A Retrospective Study. Acta Med Iran. 2022;60(1):32-39.
