Clinical Implications of Cellular Ratios in SARS-CoV-2 Infection and Outcomes of COVID-19: An Integrative Literature Review

Authors

DOI:

https://doi.org/10.33448/rsd-v10i16.23482

Keywords:

COVID-19; SARS-CoV-2; Inflammation; Prognosis.

Abstract

A promising tool to act as circulating biomarkers are cellular ratios, which reflect systemic inflammation and are potential predictors for mortality prognosis in various populations. Therefore, the aim of this review is to discuss the compliance of cellular relationships and their significance in COVID-19 infection. In the present study, an integrative review was conducted. After defining the guiding question, locating and selecting articles, 491 potentially eligible publications were identified. After applying the inclusion and exclusion criteria, the sample consisted of 35 articles. It was found that elevated peripheral blood cell ratios indicate unsatisfactory clinical outcome of COVID-19. Patients with these elevated cell ratios had higher incidence of acute respiratory distress syndrome, higher rate of need for mechanical ventilation, and higher mortality rates. In conclusion, it was found that there was an association between the quantitative value of the cell ratios with the evolution of the patient with COVID-19. It was observed that the higher the neutrophil/lymphocyte, platelet/lymphocyte, and lymphocyte/monocyte ratios, the worse the prognosis of the patient infected with SARS-CoV 2. Further research is needed to confirm these findings and to compare the predictive ability of the ratios in the evolution of COVID-19 infection.

References

Borger, B. et al. Systematic review with meta-analysis of the accuracy of diagnostic tests for COVID-19. American journal of infection control, 2020.

Fang, X. et al. Epidemiological, comorbidity factors with severity and prognosis of COVID-19: a systematic review and meta-analysis. Aging (Albany NY), v. 12, n. 13, p. 12493, 2020.

Fu, J., Kong, J., Wang, W., Wu, M., Yao, L., Wang, Z., Jin, J., Wu, D., Yu, X. 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. Epub 2020 May 6. PMID: 32407937; PMCID: PMC7201241.

Lauer, S. A. et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Annals of internal medicine, v. 172, n. 9, p. 577-582, 2020

Gallo, M., B. et al. Predictors of COVID‐19 severity: A literature review. Reviews in medical virology, v. 31, n. 1, p. 1-10, 2021.

Ponti, G., Maccaferri, M., Ruini, C., Tomasi, A., Ozben, T. Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci. 2020 Sep;57(6):389-399. doi: 10.1080/10408363.2020.1770685. Epub 2020 Jun 5. PMID: 32503382; PMCID: PMC7284147.

Liu, Y., Du, X., Chen, J., Jin, Y., Peng, L., Wang, H., Luo, M., Chen, L., & Zhao, Y. (2020). Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. The Journal of infection, 81(1), e6–e12. https://doi.org/10.1016/j.jinf.2020.04.002

Fu, J., Kong, J., Wang, W., Wu, M., Yao, L., Wang, Z., Jin, J., Wu, D., & Yu, X. (2020). The clinical implication of dynamic neutrophil to lymphocyte ratio and D-dimer in COVID-19: A retrospective study in Suzhou China. Thrombosis research, 192, 3–8. https://doi.org/10.1016/j.thromres.2020.05.006

Tatum, D., Taghavi, S., Houghton, A., Stover, J., Toraih, E., & Duchesne, J. (2020). Neutrophil-to-Lymphocyte Ratio and Outcomes in Louisiana COVID-19 Patients. Shock (Augusta, Ga.), 54(5), 652–658. https://doi.org/10.1097/SHK.0000000000001585

Basbus, L., Lapidus, M. I., Martingano, I., Puga, M. C., & Pollán, J. (2020). índice neutrófilo-linfocito como factor pronóstico de COVID-19 [Neutrophil to lymphocyte ratio as a prognostic marker in COVID-19]. Medicina, 80 Suppl 3, 31–36.

Ye, W., Chen, G., Li, X., Lan, X., Ji, C., Hou, M., Zhang, D., Zeng, G., Wang, Y., Xu, C., Lu, W., Cui, R., Cai, Y., Huang, H., & Yang, L. (2020). Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19. Respiratory research, 21(1), 169. https://doi.org/10.1186/s12931-020-01428-7

Ma, A., Cheng, J., Yang, J., Dong, M., Liao, X., & Kang, Y. (2020). Neutrophil-to-lymphocyte ratio as a predictive biomarker for moderate-severe ARDS in severe COVID-19 patients. Critical care (London, England), 24(1), 288. https://doi.org/10.1186/s13054-020-03007-0

Yang, A. P., Liu, J. P., Tao, W. Q., & Li, H. M. (2020). The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. International immunopharmacology, 84, 106504. https://doi.org/10.1016/j.intimp.2020.106504

Chan, A. S., & Rout, A. (2020). Use of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in COVID-19. Journal of clinical medicine research, 12(7), 448–453. https://doi.org/10.14740/jocmr4240

Ciccullo, A., Borghetti, A., Zileri Dal Verme, L., Tosoni, A., Lombardi, F., Garcovich, M., Biscetti, F., Montalto, M., Cauda, R., Di Giambenedetto, S., & Gemelli against COVID Group (2020). Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the Italian front line. International journal of antimicrobial agents, 56(2), 106017. https://doi.org/10.1016/j.ijantimicag.2020.106017

Wang, H., Zhang, Y., Mo, P., Liu, J., Wang, H., Wang, F., & Zhao, Q. (2020). Neutrophil to CD4+ lymphocyte ratio as a potential biomarker in predicting virus negative conversion time in COVID-19. International immunopharmacology, 85, 106683. https://doi.org/10.1016/j.intimp.2020.106683

Seyit, M., Avci, E., Nar, R., Senol, H., Yilmaz, A., Ozen, M., Oskay, A., & Aybek, H. (2021). Neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio and platelet to lymphocyte ratio to predict the severity of COVID-19. The American journal of emergency medicine, 40, 110–114. https://doi.org/10.1016/j.ajem.2020.11.058

Liu, J., Liu, Y., Xiang, P., Pu, L., Xiong, H., Li, C., Zhang, M., Tan, J., Xu, Y., Song, R., Song, M., Wang, L., Zhang, W., Han, B., Yang, L., Wang, X., Zhou, G., Zhang, T., Li, B., Wang, Y., … Wang, X. (2020). Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. Journal of translational medicine, 18(1), 206. https://doi.org/10.1186/s12967-020-02374-0

Jimeno, S., Ventura, P. S., Castellano, J. M., García-Adasme, S. I., Miranda, M., Touza, P., Lllana, I., & López-Escobar, A. (2021). Prognostic implications of neutrophil-lymphocyte ratio in COVID-19. European journal of clinical investigation, 51(1), e13404. https://doi.org/10.1111/eci.13404

Kong, M., Zhang, H., Cao, X., Mao, X., & Lu, Z. (2020). Higher level of neutrophil-to-lymphocyte is associated with severe COVID-19. Epidemiology and infection, 148, e139. https://doi.org/10.1017/S0950268820001557

Lian, J., Jin, C., Hao, S., Zhang, X., Yang, M., Jin, X., Lu, Y., Hu, J., Zhang, S., Zheng, L., Jia, H., Cai, H., Zhang, Y., Yu, G., Wang, X., Gu, J., Ye, C., Yu, X., Gao, J., Yang, Y., … Sheng, J. (2020). High neutrophil-to-lymphocyte ratio associated with progression to critical illness in older patients with COVID-19: a multicenter retrospective study. Aging, 12(14), 13849–13859. https://doi.org/10.18632/aging.103582

Cai, J., Li, H., Zhang, C., Chen, Z., Liu, H., Lei, F., Qin, J. J., Liu, Y. M., Zhou, F., Song, X., Zhou, J., Zhao, Y. C., Wu, B., He, M., Yang, H., Zhu, L., Zhang, P., Ji, Y. X., Zhao, G. N., Lu, Z., … Li, H. (2021). The Neutrophil-to-Lymphocyte Ratio Determines Clinical Efficacy of Corticosteroid Therapy in Patients with COVID-19. Cell metabolism, 33(2), 258–269.e3. https://doi.org/10.1016/j.cmet.2021.01.002

Bedel, C., & Korkut, M. (2020). Neutrophil-To-Lymphocyte Ratio And Covid-19. Shock (Augusta, Ga.), Publish Ahead of Print, 10.1097/SHK.0000000000001712. Advance online publication. https://doi.org/10.1097/SHK.0000000000001712

Rizo-Téllez, S. A., Méndez-García, L. A., Flores-Rebollo, C., Alba-Flores, F., Alcántara-Suárez, R., Manjarrez-Reyna, A. N., Baltazar-López, N., Hernández-Guzmán, V. A., León-Pedroza, J. I., Zapata-Arenas, R., González-Chávez, A., Hernández-Ruíz, J., Carrillo-Ruíz, J. D., Serrano-Loyola, R., Guerrero-Avendaño, G., & Escobedo, G. (2020). The Neutrophil-to-Monocyte Ratio and Lymphocyte-to-Neutrophil Ratio at Admission Predict In-Hospital Mortality in Mexican Patients with Severe SARS-CoV-2 Infection (Covid-19). Microorganisms, 8(10), 1560. https://doi.org/10.3390/microorganisms8101560

Yan, X., Li, F., Wang, X., Yan, J., Zhu, F., Tang, S., Deng, Y., Wang, H., Chen, R., Yu, Z., Li, Y., Shang, J., Zeng, L., Zhao, J., Guan, C., Liu, Q., Chen, H., Gong, W., Huang, X., Zhang, Y. J., Li, D. (2020). Neutrophil to lymphocyte ratio as prognostic and predictive factor in patients with coronavirus disease 2019: A retrospective cross-sectional study. Journal of medical virology, 92(11), 2573–2581. https://doi.org/10.1002/jmv.26061

Xu, J. B., Xu, C., Zhang, R. B., Wu, M., Pan, C. K., Li, X. J., Wang, Q., Zeng, F. F., & Zhu, S. (2020). Associations of procalcitonin, C-reaction protein and neutrophil-to-lymphocyte ratio with mortality in hospitalized COVID-19 patients in China. Scientific reports, 10(1), 15058. https://doi.org/10.1038/s41598-020-72164-7

Zhang, B., Zhou, X., Zhu, C., Song, Y., Feng, F., Qiu, Y., Feng, J., Jia, Q., Song, Q., Zhu, B., & Wang, J. (2020). Immune Phenotyping Based on the Neutrophil-to-Lymphocyte Ratio and IgG Level Predicts Disease Severity and Outcome for Patients With COVID-19. Frontiers in molecular biosciences, 7, 157. https://doi.org/10.3389/fmolb.2020.00157

Nalbant, A., Kaya, T., Varim, C., Yaylaci, S., Tamer, A., & Cinemre, H. (2020). Can the neutrophil/lymphocyte ratio (NLR) have a role in the diagnosis of coronavirus 2019 disease (COVID-19)?. Revista da Associacao Medica Brasileira (1992), 66(6), 746–751. https://doi.org/10.1590/1806-9282.66.6.746

Wang, X., Li, X., Shang, Y., Wang, J., Zhang, X., Su, D., Zhao, S., Wang, Q., Liu, L., Li, Y., & Chen, H. (2020). Ratios of neutrophil-to-lymphocyte and platelet-to-lymphocyte predict all-cause mortality in inpatients with coronavirus disease 2019 (COVID-19): a retrospective cohort study in a single medical centre. Epidemiology and infection, 148, e211. https://doi.org/10.1017/S0950268820002071

Liu, Y. P., Li, G. M., He, J., Liu, Y., Li, M., Zhang, R., Li, Y. L., Wu, Y. Z., & Diao, B. (2020). Combined use of the neutrophil-to-lymphocyte ratio and CRP to predict 7-day disease severity in 84 hospitalized patients with COVID-19 pneumonia: a retrospective cohort study. Annals of translational medicine, 8(10), 635. https://doi.org/10.21037/atm-20-2372

Qun, S., Wang, Y., Chen, J., Huang, X., Guo, H., Lu, Z., Wang, J., Zheng, C., Ma, Y., Zhu, Y., Xia, D., Wang, Y., He, H., Wang, Y., Fei, M., Yin, Y., Zheng, M., Xu, Y., Ge, W., Hu, F., … Zhou, J. (2020). Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19. Frontiers in immunology, 11, 2160. https://doi.org/10.3389/fimmu.2020.02160

Liu, L., Zheng, Y., Cai, L., Wu, W., Tang, S., Ding, Y., Liu, W., Kou, G., Xiong, Z., Wang, S., & Zheng, S. (2021). Neutrophil-to-lymphocyte ratio, a critical predictor for assessment of disease severity in patients with COVID-19. International journal of laboratory hematology, 43(2), 329–335. https://doi.org/10.1111/ijlh.13374

Pimentel, G. D., Dela Vega, M., & Laviano, A. (2020). High neutrophil to lymphocyte ratio as a prognostic marker in COVID-19 patients. Clinical nutrition ESPEN, 40, 101–102. https://doi.org/10.1016/j.clnesp.2020.08.004

Eslamijouybari, M., Heydari, K., Maleki, I., Moosazadeh, M., Hedayatizadeh-Omran, A., Vahedi, L., Ghasemian, R., Sharifpour, A., & Alizadeh-Navaei, R. (2020). Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in COVID-19 Patients and Control Group and Relationship with Disease Prognosis. Caspian journal of internal medicine, 11(Suppl 1), 531–535. https://doi.org/10.22088/cjim.11.0.531

Mousavi-Nasab, S. D., Mardani, R., Nasr Azadani, H., Zali, F., Ahmadi Vasmehjani, A., Sabeti, S., Alavi Darazam, I., & Ahmadi, N. (2020). Neutrophil to lymphocyte ratio and C-reactive protein level as prognostic markers in mild versus severe COVID-19 patients. Gastroenterology and hepatology from bed to bench, 13(4), 361–366.

Vafadar Moradi, E., Teimouri, A., Rezaee, R., Morovatdar, N., Foroughian, M., Layegh, P., Rezvani Kakhki, B., Ahmadi Koupaei, S. R., & Ghorani, V. (2021). Increased age, neutrophil-to-lymphocyte ratio (NLR) and white blood cells count are associated with higher COVID-19 mortality. The American journal of emergency medicine, 40, 11–14. https://doi.org/10.1016/j.ajem.2020.12.003

Carpio-Orantes, L. D., García-Méndez, S., & Hernández-Hernández, S. N. (2020). Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in patients with COVID-19-associated pneumonia. Índices neutrófilo/linfocito, plaqueta/linfocito e inmunidad/inflamación sistémica en pacientes con neumonía por COVID-19. Gaceta medica de Mexico, 156(6), 527–531. https://doi.org/10.24875/GMM.M21000480

Yufei, Y., Mingli, L., Xuejiao, L., Xuemei, D., Yiming, J., Qin, Q., Hui, S., & Jie, G. (2020). Utility of the neutrophil-to-lymphocyte ratio and C-reactive protein level for coronavirus disease 2019 (COVID-19). Scandinavian journal of clinical and laboratory investigation, 80(7), 536–540. https://doi.org/10.1080/00365513.2020.1803587

Haghjooy Javanmard, S., Vaseghi, G., Manteghinejad, A., & Nasirian, M. (2020). Neutrophil-to-Lymphocyte ratio as a potential biomarker for disease severity in COVID-19 patients. Journal of global antimicrobial resistance, 22, 862–863. https://doi.org/10.1016/j.jgar.2020.07.029

Belice, T., Demir, I., & Yüksel, A. (2020). Role of neutrophil-lymphocyte-ratio in the mortality of males diagnosed with COVID-19. Iranian journal of microbiology, 12(3), 194–197.

Albarrán-Sánchez, A., González-Ríos, R. D., Alberti-Minutti, P., Noyola-García, M. E., Contreras-García, C. E., Anda-Garay, J. C., Martínez-Ascencio, L. E., Castillo-López, D. J., Reyes-Naranjo, L. A., Guízar-García, L. A., Flores-Padilla, G., & Ramírez-Rentería, C. (2020). Association of neutrophil-to-lymphocyte and lymphocyte-to-C-reactive protein ratios with COVID-19-related mortality. Asociación de los índices neutrófilo/linfocito y linfocito/proteína C reactiva con mortalidad por COVID-19. Gaceta medica de Mexico, 156(6), 553–558. https://doi.org/10.24875/GMM.M21000481

Seyit, M., Avci, E., Nar, R., Senol, H., Yilmaz, A., Ozen, M., Oskay, A., & Aybek, H. (2021). Neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio and platelet to lymphocyte ratio to predict the severity of COVID-19. The American journal of emergency medicine, 40, 110–114. https://doi.org/10.1016/j.ajem.2020.11.058

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10/12/2021

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CRUVINEL, M. F. S. .; SILVA, D. de L. .; SILVA, T. F. da .; HILLADES, M. V. P. .; BERNARDES, T. S. .; ABDALLA, M. R. .; ABDALLA, D. R. Clinical Implications of Cellular Ratios in SARS-CoV-2 Infection and Outcomes of COVID-19: An Integrative Literature Review. Research, Society and Development, [S. l.], v. 10, n. 16, p. e164101623482, 2021. DOI: 10.33448/rsd-v10i16.23482. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/23482. Acesso em: 22 nov. 2024.

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Vol. 10 No. 16

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Health Sciences

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Copyright (c) 2021 Mônica Ferreira Silva Cruvinel; Davi de Lima Silva; Thaís Ferreira da Silva; Maria Vitória Pereira Hillades; Tiago Soares Bernardes; Michel Reis Abdalla; Douglas Reis Abdalla

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