Neutrophil-to-Lymphocyte Ratio (NLR) Is a Promising Predictor of Mortality and Admission to Intensive Care Unit of COVID-19 Patients
Abstract
:1. Introduction
2. Methods
2.1. Subjects
- No past or present medical history of chronic illness affecting leukocyte formula (i.e., autoimmune diseases, malignancies, inflammatory chronic diseases);
- No previous chronic pharmacological treatment affecting leukocyte formula before admission to the hospital;
- Availability of at least two complete blood counts and blood gas tests;
- Hospitalization > 48 h.
2.2. Statistical Analysis
3. Results
Steroid Treatment
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
CRP | C-Reactive Protein |
D-NLR | Derived-Neutrophil-to-Lymphocyte Ratio |
ICU | Intensive Care Unit |
NLR | Neutrophil-to-Lymphocyte Ratio |
PLR | Platelet-to-Lymphocyte Ratio |
WBC | White Blood Cells |
References
- Chen, N.; Zhou, M.; Dong, X.; Qu, J.; Gong, F.; Han, Y.; Qiu, Y.; Wang, J.; Liu, Y.; Wei, Y.; et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020, 395, 507–513. [Google Scholar] [CrossRef] [Green Version]
- Wang, D.; Hu, B.; Hu, C.; Zhu, F.; Liu, X.; Zhang, J.; Wang, B.; Xiang, H.; Cheng, Z.; Xiong, Y.; et al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020, 323, 1061–1069. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Wang, X.; Jia, X.; Li, J.; Hu, K.; Chen, G.; Wei, J.; Gong, Z.; Zhou, C.; Yu, H.; et al. Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China. Clin. Microbiol. Infect. 2020, 26, 767–772. [Google Scholar] [CrossRef] [PubMed]
- Lanini, S.; Montaldo, C.; Nicastri, E.; Vairo, F.; Agrati, C.; Petrosillo, N.; Scognamiglio, P.; Antinori, A.; Puro, V.; Di Caro, A.; et al. COVID-19 disease-Temporal analyses of complete blood count parameters over course of illness, and relationship to patient demographics and management outcomes in survivors and non-survivors: A longitudinal descriptive cohort study. PLoS ONE 2020, 15, e0244129. [Google Scholar] [CrossRef]
- Zhu, Z.; Cai, T.; Fan, L.; Lou, K.; Hua, X.; Huang, Z.; Gao, G. Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Int. J. Infect. Dis. 2020, 95, 332–339. [Google Scholar] [CrossRef]
- Cataudella, E.; Giraffa, C.M.; Di Marca, S.; Pulvirenti, A.; Alaimo, S.; Pisano, M.; Terranova, V.; Corriere, T.; Ronsisvalle, M.L.; Di Quattro, R.; et al. Neutrophil-To-Lymphocyte Ratio: An Emerging Marker Predicting Prognosis in Elderly Adults with Community-Acquired Pneumonia. J. Am. Geriatr. Soc. 2017, 65, 1796–1801. [Google Scholar] [CrossRef]
- Banna, G.L.; Di Quattro, R.; Malatino, L.; Fornarini, G.; Addeo, A.; Maruzzo, M.; Urzia, V.; Rundo, F.; Lipari, H.; De Giorgi, U.; et al. Neutrophil-to-lymphocyte ratio and lactate dehydrogenase as biomarkers for urothelial cancer treated with immunotherapy. Clin. Transl. Oncol. 2020, 22, 2130–2135. [Google Scholar] [CrossRef]
- Corriere, T.; Di Marca, S.; Cataudella, E.; Pulvirenti, A.; Alaimo, S.; Stancanelli, B.; Malatino, L. Neutrophil-to-Lymphocyte Ratio is a strong predictor of atherosclerotic carotid plaques in older adults. Nutr. Metab. Cardiovasc. Dis. 2018, 28, 23–27. [Google Scholar] [CrossRef]
- Zahorec, R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl. Lek. Listy. 2021, 122, 474–488. [Google Scholar] [CrossRef]
- Zahorec, R. Ratio of neutrophil to lymphocyte counts–rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl. Lek. Listy. 2001, 102, 5–14. [Google Scholar]
- Codd, A.S.; Hanna, S.J.; Compeer, E.B.; Richter, F.C.; Pring, E.J.; Gea-Mallorquí, E.; Borsa, M.; Moon, O.R.; Scourfield, D.O.; The Oxford-Cardiff COVID-19 Literature Consortium; et al. Neutrophilia, lymphopenia and myeloid dysfunction: A living review of the quantitative changes to innate and adaptive immune cells which define COVID-19 pathology. Oxford Open Immunol. 2021, 1, iqab016. [Google Scholar] [CrossRef]
- Hu, B.; Huang, S.; Yin, L. The cytokine storm and COVID-19. J. Med. Virol. 2021, 93, 250–256. [Google Scholar] [CrossRef] [PubMed]
- Guan, W.J.; Liang, W.H.; He, J.X.; Zhong, N.S. Cardiovascular comorbidity and its impact on patients with COVID-19. Eur. Respir. J. 2020, 55, 2001227. [Google Scholar] [CrossRef] [PubMed]
- Hypertension and COVID-19. Available online: https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Hypertension-2021.1 (accessed on 20 October 2021).
- Luo, X.; Zhou, W.; Yan, X.; Guo, T.; Wang, B.; Xia, H.; Ye, L.; Xiong, J.; Jiang, Z.; Liu, Y.; et al. Prognostic Value of C-Reactive Protein in Patients With Coronavirus 2019. Clin. Infect. Dis. 2020, 71, 2174–2179. [Google Scholar] [CrossRef]
- Lazzerini, P.E.; Acampa, M.; Laghi-Pasini, F.; Bertolozzi, I.; Finizola, F.; Vanni, F.; Natale, M.; Bisogno, S.; Cevenini, G.; Cartocci, A.; et al. Cardiac Arrest Risk During Acute Infections: Systemic Inflammation Directly Prolongs QTc Interval via Cytokine-Mediated Effects on Potassium Channel Expression. Circ. Arrhythm. Electrophysiol. 2020, 13, 8. [Google Scholar] [CrossRef]
- Ullah, W.; Basyal, B.; Tariq, S.; Almas, T.; Saeed, R.; Roomi, S.; Haq, S.; Madara, J.; Boigon, M.; Haas, D.C.; et al. Lymphocyte-to-C-Reactive Protein Ratio: A Novel Predictor of Adverse Outcomes in COVID-19. J. Clin. Med. Res. 2020, 12, 415–422. [Google Scholar] [CrossRef]
- Liu, S.; Wang, X.; She, F.; Zhang, W.; Liu, H.; Zhao, X. Effects of Neutrophil-to-Lymphocyte Ratio Combined With Interleukin-6 in Predicting 28-Day Mortality in Patients With Sepsis. Front. Immunol. 2021, 12, 757. [Google Scholar] [CrossRef]
- Han, Q.; Wen, X.; Wang, L.; Han, X.; Shen, Y.; Cao, J.; Peng, Q.; Xu, J.; Zhao, L.; He, 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. [Google Scholar] [CrossRef]
- Citu, C.; Gorun, F.; Motoc, A.; Sas, I.; Gorun, O.M.; Burlea, B.; Tuta-Sas, I.; Tomescu, L.; Neamtu, R.; Malita, D.; et al. The Predictive Role of NLR, d-NLR, MLR, and SIRI in COVID-19 Mortality. Diagnostics 2022, 12, 122. [Google Scholar] [CrossRef]
- 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, 32–39. [Google Scholar] [CrossRef]
- Xu, Z.; Shi, L.; Wang, Y.; Zhang, J.; Huang, L.; Zhang, C.; Liu, S.; Zhao, P.; Liu, H.; Zhu, L.; et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020, 8, 420–422. [Google Scholar] [CrossRef]
- Santoro, F.; Guastafierro, F.; Zimotti, T.; Mallardi, A.; Leopizzi, A.; Cannone, M.; Di Biase, M.; Brunetti, N.D. Neutrophil/lymphocyte ratio predicts in-hospital complications in Takotsubo syndrome. Results from a prospective multi-center registry. Clin. Cardiol. 2020, 43, 1294–1300. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.H.; Song, S.; Yoon, S.Y.; Lim, C.S.; Song, J.W.; Kim, H.S. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as diagnostic markers for pneumonia severity. Br. J. Biomed. Sci. 2016, 73, 140–142. [Google Scholar] [CrossRef] [PubMed]
- Tan, L.; Wang, Q.; Zhang, D.; Ding, J.; Huang, Q.; Tang, Y.-Q.; Wang, Q.; Miao, H. Lymphopenia predicts disease severity of COVID-19: A descriptive and predictive study. Signal Transduct. Target Ther. 2020, 5, 33. [Google Scholar] [CrossRef] [PubMed]
- Hanley, B.; Lucas, S.B.; Youd, E.; Swift, B.; Osborn, M. Autopsy in suspected COVID-19 cases. J. Clin. Pathol. 2020, 73, 239–242. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khalid, I.; Alraddadi, B.; Bawareth, N.; Omar, H.; AlSalmi, H.; Alshukairi, A.; Qushmaq, I.; Feteih, M.; Qutob, M.; Wali, G. Patient characteristics infected with Middle East respiratory syndrome coronavirus infection in a tertiary hospital. Ann. Thorac. Med. 2016, 11, 128–131. [Google Scholar] [CrossRef] [PubMed]
- Terpos, E.; Ntanasis-Stathopoulos, I.; Elalamy, I.; Kastritis, E.; Sergentanis, T.N.; Politou, M.; Psaltopoulou, T.; Gerotziafas, G.; Dimopoulos, M.A. Hematological findings and complications of COVID-19. Am. J. Hematol. 2020, 95, 834–847. [Google Scholar] [CrossRef] [Green Version]
- Qu, R.; Ling, Y.; Zhang, Y.H.; Wei, L.; Chen, X.; Li, X.; Liu, X.; Liu, H.; Guo, Z.; Ren, H.; et al. Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19. J. Med. Virol. 2020, 92, 1533–1541. [Google Scholar] [CrossRef]
- Qin, B.; Ma, N.; Tang, Q.; Wei, T.; Yang, M.; Fu, H.; Hu, Z.; Liang, Y.; Yang, Z.; Zhong, R. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod. Rheumatol. 2016, 26, 372–376. [Google Scholar] [CrossRef]
- Fois, A.G.; Paliogiannis, P.; Scano, V.; Cau, S.; Babudieri, S.; Perra, R.; Ruzzittu, G.; Zinellu, E.; Pirina, P.; Carru, C.; et al. The Systemic Inflammation Index on Admission Predicts In-Hospital Mortality in COVID-19 Patients. Molecules 2020, 25, 5725. [Google Scholar] [CrossRef]
- Kalabin, A.; Mani, V.R.K.; Valdivieso, S.C.; Donaldson, B. Role of neutrophil-to-lymphocyte, lymphocyte-to-monocyte and platelet-to-lymphocyte ratios as predictors of disease severity in COVID-19 patients. Infez Med. 2021, 29, 46–53. [Google Scholar] [PubMed]
- Nurlu, N.; Ozturk, O.O.; Cat, A.; Altunok, E.S.; Gumus, A. Could Some Laboratory Parameters Predict Mortality in COVID-19? Clin. Lab. 2021, 67. [Google Scholar] [CrossRef] [PubMed]
- Mousavi, S.A.; Rad, S.; Rostami, T.; Rostami, M.; Mousavi, S.A.; Mirhoseini, S.A.; Kiumarsi, A. Hematologic predictors of mortality in hospitalized patients with COVID-19: A comparative study. Hematology 2020, 25, 383–388. [Google Scholar] [CrossRef] [PubMed]
- Eslamijouybari, M.; Heydari, K.; Maleki, I.; Moosazadeh, M.; Hedayatizadeh-Omran, A.; Vahedi, L.; Ghasemian, R.; Sharifpour, A.; Alizadeh-Navaei, R. Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in COVID-19 Patients and Control Group and Relationship with Disease Prognosis. Caspian J. Intern. Med. 2020, 11 (Suppl. S1), 531–535. [Google Scholar] [CrossRef] [PubMed]
- Sarkar, S.; Kannan, S.; Khanna, P.; Singh, A.K. Role of platelet-to-lymphocyte count ratio (PLR), as a prognostic indicator in COVID-19: A systematic review and meta-analysis. J. Med. Virol. 2022, 94, 211–221. [Google Scholar] [CrossRef] [PubMed]
- Yang, A.P.; Liu, J.P.; Tao, W.Q.; Li, H.M. The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. Int. Immunopharmacol. 2020, 84. [Google Scholar] [CrossRef]
- Abensur Vuillaume, L.; Le Borgne, P.; Alamé, K.; Lefebvre, F.; Bérard, L.; Delmas, N.; Cipolat, L.; Gennai, S.; Bilbault, P.; Lavoignet, C.-E.; et al. Neutrophil-to-Lymphocyte Ratio and Early Variation of NLR to Predict In-Hospital Mortality and Severity in ED Patients with SARS-CoV-2 Infection. J. Clin. Med. 2021, 10, 2563. [Google Scholar] [CrossRef]
Low Flow Oxygen Therapy | High Flow Oxygen Therapy | NIMV | |||||||
---|---|---|---|---|---|---|---|---|---|
Nasal Cannula | Venturi Mask | Venturi Mask | HFNC | C-PAP | NIV | ||||
1–3 L/min (FiO2 = 0.24–0.32) | 4–6 L/min (FiO2 = 0.36–0.44) | 4–8 L/min (FiO2 = 0.24–0.35) | 10–12 L/min (FiO2 = 0.40–0.60) | FiO2 = 0.40–0.60 | FiO2 <= 0.40 | FiO2 = 0.41–0.50 | FiO2 = 0.51–0.60 | ||
Patients, n | 29 | 26 | 65 | 39 | 47 | 16 | 58 | 30 | 32 |
PaO2/FiO2 | 237.8 (193.8–281.2) | 162.43 (121–218.8) | 119.9 (92.5–151) * |
Total (n = 411) | 1st Tertile (n = 137) | 2nd Tertile (n = 137) | 3rd Tertile (n = 137) | p | |
---|---|---|---|---|---|
Age, y | 72 (70–75) | 67 (61–69) | 71 (68–74) | 80 (77–83) | <0.000001 |
Male sex, n (%) | 237 (57.7) | 71 (51.9) | 88 (64.3) | 78 (57) | 0.1127 |
P/F | 173 (161–187) | 244 (215- 269.6) | 163 (51–184) | 129 (120–145) | <0.000001 |
WBC, 109/L | 8.8 (8.2–9.4) | 6.1 (5.8– 6.9) | 8.8 (8.4–9.7) | 11.7 (10.8–12.9) | 0.000009 |
ANC, 109/L | 7.2 (6.8–7.9) | 4.4 (4.1- 5) | 7.5 (7.1–8.2) | 10.5 (9.8–11.7) | <0.000001 |
LYMPH, 109/L | 0.73 (0.4–0.8) | 1.20 (1–1.3) | 0.76 (0.7–0.8) | 0.48 (0.4–0.5) | <0.000001 |
PLT, 109/L | 226 (217–235.8) | 215 (194.3–234.4) | 237 (221–254) | 222 (210–242.9) | 0.0553 |
CRP, mg/dL | 8.9 (8.13–9.59) | 4.9 (3.7–5.9) | 9.7 (8.4–11.2) | 13 (10.6–15) | <0.000001 |
PLR | 226 (217–235.8) | 215 (194.3–234.4) | 237 (221–254) | 222 (210–242.9) | <0.000001 |
d-NLR | 5 (5–6) | 3 (2–3) | 6 (5–6) | 10.5 (9–12) | <0.000001 |
Length of stay, days | 10 (9–11) | 8 (7–10) | 10 (8–12) | 11 (9–12) | 0.1444 |
Deceased, n (%) | 133 (19.5) | 13 (4.4) | 39 (16.8) | 81 (37.3) | <0.00001 |
ICU Admission, n (%) | 79 (19.3) | 10 (7.3) | 30 (21.9) | 39 (28.5) | 0.000032 * |
Hypertension, n (%) | 244 (59.4) | 79 (51.9) | 76 (55.5) | 89 (65) | 0.2461 |
Diabetes Mellitus, n (%) | 111 (27) | 32 (23.4) | 37 (23.4) | 42 (30.7) | 0.3962 |
CKD, n (%) | 35 (8.6) | 10 (7.3) | 9 (6.6) | 16 (11.7) | 0.2610 |
COPD, n (%) | 34 (8.3) | 11 (8.1) | 11 (8.1) | 12 (8.8) | 0.9684 |
CV Disease, n (%) | 70 (17.1) | 22 (16.1) | 18 (13.2) | 30 (21.9) | 0.1453 |
NLR | Unadjusted HR | p | Model 1 HR | p | Model 2 HR | p |
---|---|---|---|---|---|---|
1° tertile | 1.20 | 0.4902 | 1.20 | 0.4821 | 1.16 | 0.5952 |
2° tertile | 1.25 | 0.0296 | 1.28 | 0.0267 | 1.26 | 0.0314 |
3° tertile | 1.38 | 0.0009 | 1.29 | 0.0108 | 1.38 | 0.0018 |
Total | 1.62 | <0.0001 | 1.45 | <0.0001 | 1.59 | <0.0001 |
Unadjusted HR | p | Model 1 HR | p | Model 2 HR | p | |
CRP | 1.04 | <0.0001 | 1.04 | <0.0001 | 1.04 | <0.0001 |
ANC | 1.17 | <0.0001 | 1.10 | 0.0259 | 1.75 | 0.0001 |
LYMP | 0.5965 | 0.0089 | 0.7030 | 0.0437 | 0.5501 | 0.0114 |
d-NLR | 1.05 | <0.0001 | 1.03 | 0.0010 | 1.03 | 0.0106 |
PLR | 1 | 0.6800 | 1 | 0.6605 | 1 | 0.6958 |
Unadjusted HR | p | Model 1 HR | p | Model 2 HR | p | Model 3 HR | p | |
---|---|---|---|---|---|---|---|---|
NLR | 3.9597 | <0.0001 | 1.02 | 0.0035 | 1.01 | 0.0391 | 1.005 | 0.4741 |
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Regolo, M.; Vaccaro, M.; Sorce, A.; Stancanelli, B.; Colaci, M.; Natoli, G.; Russo, M.; Alessandria, I.; Motta, M.; Santangelo, N.; et al. Neutrophil-to-Lymphocyte Ratio (NLR) Is a Promising Predictor of Mortality and Admission to Intensive Care Unit of COVID-19 Patients. J. Clin. Med. 2022, 11, 2235. https://doi.org/10.3390/jcm11082235
Regolo M, Vaccaro M, Sorce A, Stancanelli B, Colaci M, Natoli G, Russo M, Alessandria I, Motta M, Santangelo N, et al. Neutrophil-to-Lymphocyte Ratio (NLR) Is a Promising Predictor of Mortality and Admission to Intensive Care Unit of COVID-19 Patients. Journal of Clinical Medicine. 2022; 11(8):2235. https://doi.org/10.3390/jcm11082235
Chicago/Turabian StyleRegolo, Matteo, Mauro Vaccaro, Alessandra Sorce, Benedetta Stancanelli, Michele Colaci, Giuseppe Natoli, Mario Russo, Innocenza Alessandria, Massimo Motta, Nicola Santangelo, and et al. 2022. "Neutrophil-to-Lymphocyte Ratio (NLR) Is a Promising Predictor of Mortality and Admission to Intensive Care Unit of COVID-19 Patients" Journal of Clinical Medicine 11, no. 8: 2235. https://doi.org/10.3390/jcm11082235