Neutrophil/Lymphocyte Ratio (NLR) and Lym-phocyte/CRP ratio (LCR) are Reliable Pre-dictors of Adverse Out-comes in High-Altitude COVID-19 Patients
Main Article Content
Abstract
The neutrophil/lymphocyte ratio (NLR) and the lymphocyte/C-reactive protein ratio (LCR) are prognostic factors in inflammatory, cardiovascular, and oncological diseases. With the emergence of the COVID-19 pandemic, it has been recently shown that NLR and LCR are also useful for the prognosis of disease severity in patients infected with the SARS-CoV-2 virus at sea level. However, there are no studies demonstrating the reliability of NLR and LCR in high-altitude human populations (above 2,500 m). This is relevant because both the incidence and mortality from COVID-19 are decreased in high altitude. A possible explanation of this effect is a lower impact of this virus on the exaggerated inflammatory response induced by the viral infection. The aim of this study is to determine whether the NLR and LCR indices can be used as reliable predictive markers of COVID-19 severity in high-altitude permanent resident patients. Routine blood biochemistry and complete blood count were performed on 368 patients positive for the SARS-CoV-2 virus in Huaraz, Peru (3,050 m). Patients’ follow up was carried out until home discharge or fatal outcome. The results show that: 1) NLR values are higher in deceased patients admitted to the intensive care unit due to COVID-19; 2) NLR and LCR are reliable predictors of death in patients with COVID-19; and 3) NLR and LCR are reliable predictors of intensive care unit requirement in COVID-19 patients. We conclude that NLR and LCR are reliable biomarkers and prognostic factors of COVID-19 severity and can be used in high-altitude permanent resident patients.
Keywords:
SARS-COV-2, high altitude, disease severity, mortality, inflammation, prognosis
Article Details
How to Cite
JIMENEZ-AGUILAR, Rosalinda et al.
Neutrophil/Lymphocyte Ratio (NLR) and Lym-phocyte/CRP ratio (LCR) are Reliable Pre-dictors of Adverse Out-comes in High-Altitude COVID-19 Patients.
Medical Research Archives, [S.l.], v. 11, n. 8, aug. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4300>. Date accessed: 13 may 2024.
doi: https://doi.org/10.18103/mra.v11i8.4300.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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4. Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ra-tio in solid tumors: a systematic review and me-ta-analysis. J Natl Cancer Inst. 2014;106(6):dju124. doi:10.1093/jnci/dju124
5. Kim S, Eliot M, Koestler DC, Wu WC, Kelsey KT. Association of Neutrophil-to-Lymphocyte Ratio With Mortality and Cardiovascular Disease in the Jackson Heart Study and Modification by the Duffy Antigen Variant. JAMA Cardiol. 2018;3(6):455-462. doi:10.1001/jamacardio.2018.1042
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7. Kong W, He Y, Bao H, Zhang W, Wang X. Di-agnostic Value of Neutrophil-Lymphocyte Ratio for Predicting the Severity of Acute Pancreatitis: A Meta-Analysis. Dis Markers. 2020;2020:9731854. doi:10.1155/2020/9731854
8. Chávez Valencia V, Orizaga de la Cruz C, Mejía Rodríguez O, Gutiérrez Castellanos S, Lagunas Rangel FA, Viveros Sandoval ME. In-flammation in hemodialysis and their correlation with neutrophi-lymphocite ratio and platelet-lymphocyte ratio. Nefrol Engl Ed. 2017;37(5):554-556. doi:10.1016/j.nefroe.2016.12.014
9. Valga F, Monzón T, Henriquez F, Antón-Pérez G. Índices neutrófilo-linfocito y plaqueta-linfocito como marcadores biológicos de interés en la enfermedad renal. Nefrología. 2019;39(3):243-249. doi:10.1016/j.nefro.2018.11.005
10. Stojkovic Lalosevic M, Pavlovic Markovic A, Stankovic S, et al. Combined Diagnostic Effica-cy of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Mean Platelet Volume (MPV) as Biomarkers of System-ic Inflammation in the Diagnosis of Colorectal Cancer. Dis Markers. 2019;2019:6036979. doi:10.1155/2019/6036979
11. Lian J, jin C, Hao S, et al. High neutrophil-to-lymphocyte ratio associated with progression to critical illness in older patients with COVID-19: a multicenter retrospective study. Aging. 2020;12(14):13849-13859. doi:10.18632/aging.103582
12. Zhang JJ, Cao YY, Tan G, et al. Clinical, radio-logical, and laboratory characteristics and risk factors for severity and mortality of 289 hospi-talized COVID-19 patients. Allergy. 2021;76(2):533-550. doi:10.1111/all.14496
13. Fu J, Kong J, Wang W, et al. The clinical impli-cation of dynamic neutrophil to lymphocyte ra-tio and D-dimer in COVID-19: A retrospective study in Suzhou China. Thromb Res. 2020;192:3-8. doi:10.1016/j.thromres.2020.05.006
14. Liao D, Zhou F, Luo L, et al. Haematological characteristics and risk factors in the classifica-tion and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Haematol. 2020;7(9):e671-e678. doi:10.1016/S2352-3026(20)30217-9
15. Nalbant A, Kaya T, Varim C, Yaylaci S, Tamer A, Cinemre H. Can the neutrophil/lymphocyte ratio (NLR) have a role in the diagnosis of coro-navirus 2019 disease (COVID-19)? Rev Assoc Médica Bras. 2020;66:746-751. doi:10.1590/1806-9282.66.6.746
16. Ma A, Cheng J, Yang J, Dong M, Liao X, Kang Y. Neutrophil-to-lymphocyte ratio as a predic-tive biomarker for moderate-severe ARDS in se-vere COVID-19 patients. Crit Care. 2020;24:288. doi:10.1186/s13054-020-03007-0
17. Albarrán-Sánchez A, González-Ríos RD, Alberti-Minutti P, et al. Asociación de los índices neu-trófilo/linfocito y linfocito/proteína C reactiva con mortalidad por COVID-19. Gac Médica México. 2020;156(6):563-568. doi:10.24875/gmm.20000525
18. Nishi M, Shimada M, Tokunaga T, et al. Lym-phocyte to C-reactive protein ratio predicts long-term outcomes for patients with lower rec-tal cancer. World J Surg Oncol. 2021;19:201. doi:10.1186/s12957-021-02319-x
19. Ullah W, Basyal B, Tariq S, et al. Lymphocyte-to-C-Reactive Protein Ratio: A Novel Predictor of Adverse Outcomes in COVID-19. J Clin Med Res. 2020;12(7):415-422. doi:10.14740/jocmr4227
20. Kosidło JW, Wolszczak-Biedrzycka B, Ma-towicka-Karna J, Dymicka-Piekarska V, Dorf J. Clinical Significance and Diagnostic Utility of NLR, LMR, PLR and SII in the Course of COVID-19: A Literature Review. J Inflamm Res. 2023;16:539-562. doi:10.2147/JIR.S395331
21. Afari ME, Bhat T. Neutrophil to lymphocyte ratio (NLR) and cardiovascular diseases: an update. Expert Rev Cardiovasc Ther. 2016;14(5):573-577. doi:10.1586/14779072.2016.1154788
22. Faria SS, Fernandes PC, Silva MJB, et al. The neutrophil-to-lymphocyte ratio: a narrative re-view. Ecancermedicalscience. 2016;10:702. doi:10.3332/ecancer.2016.702
23. Akilli NB, Yortanlı M, Mutlu H, et al. Prognostic importance of neutrophil-lymphocyte ratio in critically ill patients: short- and long-term out-comes. Am J Emerg Med. 2014;32(12):1476-1480. doi:10.1016/j.ajem.2014.09.001
24. Lagunas-Rangel FA. Neutrophil-to-lymphocyte ratio and lymphocyte-to-C-reactive protein ra-tio in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. J Med Vi-rol. 2020;92(10):1733-1734. doi:10.1002/jmv.25819
25. Liu J, Liu Y, Xiang P, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J Transl Med. 2020;18(1):206. doi:10.1186/s12967-020-02374-0
26. Gandino IJ, Padilla MJ, Carreras M, et al. [Lymphocyte-to-C-reactive protein ratio in COVID-19: an unexplored tool]. Medicina (Mex). 2022;82(5):689-694.
27. Cillóniz C, Torres A, Garcia-Vidal C, et al. The Value of C-Reactive Protein-to-Lymphocyte Ra-tio in Predicting the Severity of SARS-CoV-2 Pneumonia. Arch Bronconeumol. 2021;57:79-82. doi:10.1016/j.arbres.2020.07.038
28. Zhang JN, Gao Y, Wang XT, et al. Lympho-cyte–C-reactive protein ratio can differentiate disease severity of COVID-19 patients and serve as an assistant screening tool for hospital and ICU admission. Front Immunol. 2022;13. Accessed February 25, 2023. https://www.frontiersin.org/articles/10.3389/fimmu.2022.957407
29. Arias-Reyes C, Carvajal-Rodriguez F, Poma-Machicao L, et al. Decreased incidence, virus transmission capacity, and severity of COVID-19 at altitude on the American continent. PLOS ONE. 2021;16(3):e0237294. doi:10.1371/journal.pone.0237294
30. Zubieta-Calleja G, Merino-Luna A, Zubieta-DeUrioste N, et al. Re: “Mortality Attributed to COVID-19 in High-Altitude Populations” by Woolcott and Bergman. High Alt Med Biol. 2021;22(1):102-104. doi:10.1089/ham.2020.0195
31. Millet GP, Debevec T, Brocherie F, Burtscher M, Burtscher J. Altitude and COVID-19: Friend or foe? A narrative review. Physiol Rep. 2021;8(24):e14615. doi:10.14814/phy2.14615
32. Viruez-Soto A, Arias S, Casas-Mamani R, et al. Oxygen therapy limiting peripheral oxygen saturation to 89-93% is associated with a better survival prognosis for critically ill COVID-19 pa-tients at high altitudes. Respir Physiol Neurobiol. 2022;299:103868. doi:10.1016/j.resp.2022.103868
33. Scheinfeldt LB, Tishkoff SA. Living the high life: high-altitude adaptation. Genome Biol. 2010;11(9):133. doi:10.1186/gb-2010-11-9-133
34. Zeng H, Ma Y, Zhou Z, et al. Spectrum and Clin-ical Characteristics of Symptomatic and Asymp-tomatic Coronavirus Disease 2019 (COVID-19) With and Without Pneumonia. Front Med. 2021;8. Accessed February 25, 2023. https://www.frontiersin.org/articles/10.3389/fmed.2021.645651
35. Ciccullo A, Borghetti A, Zileri Dal Verme L, et al. Neutrophil-to-lymphocyte ratio and clinical out-come in COVID-19: a report from the Italian front line. Int J Antimicrob Agents. 2020;56(2):106017. doi:10.1016/j.ijantimicag.2020.106017
36. Páramo JA. Inflammatory response in relation to COVID-19 and other prothrombotic phenotypes. Reumatol Clin. 2022;18(1):1-4. doi:10.1016/j.reumae.2020.06.007
37. Wong RSY. Inflammation in COVID-19: from pathogenesis to treatment. Int J Clin Exp Pathol. 2021;14(7):831-844.
38. Xu S wen, Ilyas I, Weng J ping. Endothelial dysfunction in COVID-19: an overview of evi-dence, biomarkers, mechanisms and potential therapies. Acta Pharmacol Sin. Published online October 17, 2022:1-15. doi:10.1038/s41401-022-00998-0
39. Song W, Gui M, Wang X, Xiang Y. Cryo-EM structure of the SARS coronavirus spike glyco-protein in complex with its host cell receptor ACE2. PLoS Pathog. 2018;14(8):e1007236. doi:10.1371/journal.ppat.1007236
40. Perlman S, Netland J. Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol. 2009;7(6):439-450. doi:10.1038/nrmicro2147
41. Qin C, Zhou L, Hu Z, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71(15):762-768. doi:10.1093/cid/ciaa248
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