Assessment of leukocyte subtypes to high-density lipoprotein-cholesterol (HDL-C) ratios as predictors of severity and mortality in COVID-19 patients
-
Hossein Hosseini
,
Marzieh Rohani-Rasaf
,
Akram Vatannejad
,
Asma kheirollahi
,
Maryam Shabani
,
Maryam Teimouri
Abstract
Objectives: Recently, the counts of leukocyte subtypes to HDL-C concentration ratios, including monocyte to HDL-C ratio (MHR), neutrophil to HDL-C ratio (NHR), lymphocyte to HDL-C (LHR) have been proposed as potential new indices of inflammation. This study aims to investigate the correlation between these indices with the severity and mortality of COVID-19.
Methods: This study is performed on 1224 non-vaccinated and hospitalized COVID-19 patients. The association between blood parameters and indices on admission with severity and mortality are analyzed using multivariate regression models. Receiver operating characteristic curves are used to compare the utility of different blood parameters.
Results: The severe patients and deceased groups show low level of HDL-C, high values of WBC, neutrophil, monocyte, eosinophil, WBC/HDL-C, NHR, MHR, LHR, and EHR compared with the mild and survivor groups, respectively (P < 0.05). Multivariate regression analysis reveals that high levels of WBC, neutrophil, WBC/HDL-C, NHR, MHR, EHR, and low levels of HDL-C are still independently associated with severity and mortality after adjusting for age, gender, and comorbidities. The correlation of LHR with severity and mortality is attenuated to insignificance. Also, patients with high eosinophil and monocyte levels have a higher risk of severe disease. According to the AUC values, the best predictors for severity are the level of WBC, neutrophil, and NHR (AUC: 0.724, 0.725, 0.724 respectively), and the best predictors for mortality are WBC/HDL-C and NHR (AUC: 0.788, 0.790 respectively).
Conclusion: In summary, low level of HDL-C and high level of WBC, neutrophil, WBC/HDL-C, NHR, MHR, and EHR which can be easily calculated from the CBC and HDL-C concentrations, may provide valuable and readily available prognostic information for severity and mortality of COVID-19.
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20. Seymour, R. and B. Henderson, Pro‐inflammatory–anti‐inflammatory cytokine dynamics mediated by cytokine‐receptor dynamics in monocytes. Mathematical Medicine and Biology, 2001. 18(2): p. 159-192.
21. Roya Jahangard , S.S.S.E., Akram Vatannejad, Reza Meshkani Autophagy protects peripheral blood mononuclear cells from high glucose-induced inflammation and apoptosis. Acta Biochimnica Iranica. 1(1): p. 40-49.
22. Mazloom, H., S. Alizadeh, P. Pasalar, E.N. Esfahani, and R. Meshkani, Downregulated microRNA-155 expression in peripheral blood mononuclear cells of type 2 diabetic patients is not correlated with increased inflammatory cytokine production. Cytokine, 2015. 76(2): p. 403-408.
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30. Chen, T., H. Chen, H. Xiao, H. Tang, Z. Xiang, X. Wang, et al., Comparison of the Value of Neutrophil to High-Density Lipoprotein Cholesterol Ratio and Lymphocyte to High-Density Lipoprotein Cholesterol Ratio for Predicting Metabolic Syndrome Among a Population in the Southern Coast of China. Diabetes Metab Syndr Obes, 2020. 13: p. 597-605.
31. Surendar, J., K. Indulekha, V. Mohan, and R. Pradeepa, Association of neutrophil-lymphocyte ratio with metabolic syndrome and its components in Asian Indians (CURES-143). Journal of Diabetes and its Complications, 2016. 30(8): p. 1525-1529.
32. Yilmaz, H., B. Ucan, M. Sayki, I. Unsal, M. Sahin, M. Ozbek, et al., Usefulness of the neutrophil-to-lymphocyte ratio to prediction of type 2 diabetes mellitus in morbid obesity. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 2015. 9(4): p. 299-304.
33. Nima Taghizadeh , S.M., Vahid Saeedi, Ladan Haghighi, Mona Nourbakhsh, Mitra Nourbakhsh, Maryam Razzaghy Azar, Association between Steroid Hormones and Insulin Resistance in Patients with Polycystic Ovary Syndrome. Acta Biochimnica Iranica, 2023. 1(1): p. 26-31.
34. Yang, L., S. Liu, J. Liu, Z. Zhang, X. Wan, B. Huang, et al., COVID-19: immunopathogenesis and Immunotherapeutics. Signal transduction and targeted therapy, 2020. 5(1): p. 128.
35. He, R., Z. Lu, L. Zhang, T. Fan, R. Xiong, X. Shen, et al., The clinical course and its correlated immune status in COVID-19 pneumonia. Journal of Clinical Virology, 2020. 127: p. 104361.
36. Lu, G. and J. Wang, Dynamic changes in routine blood parameters of a severe COVID-19 case. Clinica Chimica Acta, 2020. 508: p. 98-102.
37. Soraya, G.V. and Z.S. Ulhaq, Crucial laboratory parameters in COVID-19 diagnosis and prognosis: An updated meta-analysis. Medicina Clínica, 2020. 155(4): p. 143-151.
38. Henry, B., I. Cheruiyot, J. Vikse, V. Mutua, V. Kipkorir, J. Benoit, et al., Lymphopenia and neutrophilia at admission predicts severity and mortality in patients with COVID-19: a meta-analysis. Acta Biomed, 2020. 91(3): p. e2020008.
39. Oliveira, D.C.d., B.S. Spiri, Y.C. Schluga, J.L.P. Justus, F.D.N. Lopes Neto, and A.P.d. Azambuja, Evaluation of lymphocyte count, T-cell subsets and neutrophil-to-lymphocyte ratio as early predictors for severity and outcome of COVID-19 disease–a report from a highly complex hospital in Brazil. Hematology, Transfusion and Cell Therapy, 2023. 45(3): p. 330-337.
40. Golucci, A.P.B.S., F.A.L. Marson, A.F. Ribeiro, and R.J.N. Nogueira, Lipid profile associated with the systemic inflammatory response syndrome and sepsis in critically ill patients. Nutrition, 2018. 55: p. 7-14.
41. Catapano, A.L., A. Pirillo, F. Bonacina, and G.D. Norata, HDL in innate and adaptive immunity. Cardiovascular research, 2014. 103(3): p. 372-383.
42. Murphy, A.J., K.J. Woollard, A. Suhartoyo, R.A. Stirzaker, J. Shaw, D. Sviridov, et al., Neutrophil activation is attenuated by high-density lipoprotein and apolipoprotein AI in in vitro and in vivo models of inflammation. Arteriosclerosis, thrombosis, and vascular biology, 2011. 31(6): p. 1333-1341.
43. Wang, S.-h., S.-g. Yuan, D.-q. Peng, and S.-p. Zhao, HDL and ApoA-I inhibit antigen presentation-mediated T cell activation by disrupting lipid rafts in antigen presenting cells. Atherosclerosis, 2012. 225(1): p. 105-114.
44. Tall, A.R. and L. Yvan-Charvet, Cholesterol, inflammation and innate immunity. Nature Reviews Immunology, 2015. 15(2): p. 104-116.
45. Argun, D., F. Argun, P. Basim, and M. Bayraktaroglu, Monocyte-to-High-Density Lipoprotein Cholesterol Ratio: a Candidate Parameter for a Risk Assessment Model in COVID-19. Clin Lab, 2022. 68(3).
46. Kou, T., H. Luo, and L. Yin, Relationship between neutrophils to HDL-C ratio and severity of coronary stenosis. BMC Cardiovascular Disorders, 2021. 21: p. 1-8.
47. Xie, J., Y. Zu, A. Alkhatib, T.T. Pham, F. Gill, A. Jang, et al., Metabolic syndrome and COVID-19 mortality among adult black patients in New Orleans. Diabetes care, 2021. 44(1): p. 188-193.
48. Adab, P., S. Haroon, M.E. O’Hara, and R.E. Jordan, Comorbidities and covid-19. 2022, British Medical Journal Publishing Group.
2. Zinellu, A. and A.A. Mangoni, Cystatin C, COVID-19 severity and mortality: a systematic review and meta-analysis. 2022. 35(1): p. 59-68.
3. Esmaeili-Nadimi, A., F. Imanparast, S. Alizadeh, A. Vatannejad, P. Mohaghegh, S.M. Seyedmehdi, et al., Total Antioxidant Capacity and Total Oxidant Status and Disease Severity in a Cohort Study of COVID-19 Patients. Clin Lab, 2023. 69(2).
4. Hossein Ghahremani, A.B., Kosar Bolandnazar , Solaleh Emamgholipor, Hossein Hosseini , Reza Meshkani Resveratrol as a Potential Protective Compound Against Metabolic Inflammation. Acta Biochimnica Iranica, 2023. 1(2): p. 50-64.
5. Zhu, B., X. Feng, C. Jiang, S. Mi, L. Yang, Z. Zhao, et al., Correlation between white blood cell count at admission and mortality in COVID-19 patients: a retrospective study. BMC Infectious Diseases, 2021. 21(1): p. 574.
6. Tanaka, S., D. Couret, A. Tran-Dinh, J. Duranteau, P. Montravers, A. Schwendeman, et al., High-density lipoproteins during sepsis: from bench to bedside. Critical Care, 2020. 24: p. 1-11.
7. Gorgani-Firuzjaee, S. and R. Meshkani, Resveratrol reduces high glucose-induced de-novo lipogenesis through mTOR mediated induction of autophagy in HepG2 cells. Acta Biochimica Iranica, 2023. 1(1): p. 32-39.
8. Parra, S., M. Saballs, M. DiNubile, M. Feliu, S. Iftimie, L. Revuelta, et al., Low HDL-c levels at admission are associated with greater severity and worse clinical outcomes in patients with COVID-19 disease. Atherosclerosis Plus, 2023. 52: p. 1-8.
9. Chen, T., H. Chen, H. Xiao, H. Tang, Z. Xiang, X. Wang, et al., Comparison of the value of neutrophil to high-density lipoprotein cholesterol ratio and lymphocyte to high-density lipoprotein cholesterol ratio for predicting metabolic syndrome among a population in the southern coast of China. Diabetes, Metabolic Syndrome and Obesity, 2020: p. 597-605.
10. Uslu, A.U., Y. Sekin, G. Tarhan, N. Canakcı, M. Gunduz, and M. Karagulle, Evaluation of monocyte to high-density lipoprotein cholesterol ratio in the presence and severity of metabolic syndrome. Clinical and Applied Thrombosis/Hemostasis, 2018. 24(5): p. 828-833.
11. Chen, H., C. Xiong, X. Shao, J. Ning, P. Gao, H. Xiao, et al., Lymphocyte to high-density lipoprotein ratio as a new indicator of inflammation and metabolic syndrome. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2019: p. 2117-2123.
12. Sun, Y., J. Lu, D. Zheng, J. Qian, H. Zhang, D. Xing, et al., Predictive value of monocyte to HDL cholesterol ratio for stroke-associated pneumonia in patients with acute ischemic stroke. Acta Neurologica Belgica, 2021. 121: p. 1575-1581.
13. Huang, J.-B., Y.-S. Chen, H.-Y. Ji, W.-M. Xie, J. Jiang, L.-S. Ran, et al., Neutrophil to high-density lipoprotein ratio has a superior prognostic value in elderly patients with acute myocardial infarction: a comparison study. Lipids in Health and Disease, 2020. 19(1): p. 1-12.
14. Wang, Y., J. Zhang, H. Li, W. Kong, J. Zheng, Y. Li, et al., Prognostic Value of Leucocyte to High-Density Lipoprotein-Cholesterol Ratios in COVID-19 Patients and the Diabetes Subgroup. Front Endocrinol (Lausanne), 2021. 12: p. 727419.
15. Rohani-Rasaf, M., K. Mirjalili, A. Vatannejad, and M. Teimouri, Are lipid ratios and triglyceride-glucose index associated with critical care outcomes in COVID-19 patients? PLoS One, 2022. 17(8): p. e0272000.
16. Espejo-Paeres, C., R.A. Espliguero, A. Uribarri, B. Antón-Huguet, R. Romero, I. Fernández-Rozas, et al., Predictors of poor prognosis in healthy, young, individuals with SARS-CoV-2 infections. Clin Microbiol Infect, 2022. 28(2): p. 273-278.
17. Agnello, L., R.V. Giglio, G. Bivona, C. Scazzone, C.M. Gambino, A. Iacona, et al., The Value of a Complete Blood Count (CBC) for Sepsis Diagnosis and Prognosis. Diagnostics (Basel), 2021. 11(10).
18. Rosales, C., Neutrophils at the crossroads of innate and adaptive immunity. Journal of Leucocyte Biology, 2020. 108(1): p. 377-396.
19. Sahar Mazloomi , M.T.G., The Relationship Between Chemerin Gene Polymorphism and the Incidence of Various Diseases. Acta Biochimnica Iranica, 2023. 1(2): p. 65-70.
20. Seymour, R. and B. Henderson, Pro‐inflammatory–anti‐inflammatory cytokine dynamics mediated by cytokine‐receptor dynamics in monocytes. Mathematical Medicine and Biology, 2001. 18(2): p. 159-192.
21. Roya Jahangard , S.S.S.E., Akram Vatannejad, Reza Meshkani Autophagy protects peripheral blood mononuclear cells from high glucose-induced inflammation and apoptosis. Acta Biochimnica Iranica. 1(1): p. 40-49.
22. Mazloom, H., S. Alizadeh, P. Pasalar, E.N. Esfahani, and R. Meshkani, Downregulated microRNA-155 expression in peripheral blood mononuclear cells of type 2 diabetic patients is not correlated with increased inflammatory cytokine production. Cytokine, 2015. 76(2): p. 403-408.
23. Wei, Y., T. Wang, G. Li, J. Feng, L. Deng, H. Xu, et al., Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder. Front Psychiatry, 2022. 13: p. 941728.
24. Cognasse, F., S. Laradi, P. Berthelot, T. Bourlet, H. Marotte, P. Mismetti, et al., Platelet inflammatory response to stress. Frontiers in immunology, 2019. 10: p. 1478.
25. Łukasik, Z.M., M. Makowski, and J.S. Makowska, From blood coagulation to innate and adaptive immunity: the role of platelets in the physiology and pathology of autoimmune disorders. Rheumatology international, 2018. 38(6): p. 959-974.
26. Aukrust, P., B. Halvorsen, T. Ueland, A.E. Michelsen, M. Skjelland, L. Gullestad, et al., Activated platelets and atherosclerosis. Expert review of cardiovascular therapy, 2010. 8(9): p. 1297-1307.
27. Russell, C.D., A. Parajuli, H.J. Gale, N.S. Bulteel, P. Schuetz, C.P. de Jager, et al., The utility of peripheral blood leucocyte ratios as biomarkers in infectious diseases: A systematic review and meta-analysis. Journal of Infection, 2019. 78(5): p. 339-348.
28. Milovanovic Alempijevic, T., M. Stojkovic Lalosevic, I. Dumic, N. Jocic, A. Pavlovic Markovic, S. Dragasevic, et al., Diagnostic accuracy of platelet count and platelet indices in noninvasive assessment of fibrosis in nonalcoholic fatty liver disease patients. Canadian Journal of Gastroenterology and Hepatology, 2017. 2017.
29. Serrano, C.V., F.R. De Mattos, F.G. Pitta, C.H. Nomura, J. De Lemos, J.A.F. Ramires, et al., Association between neutrophil-lymphocyte and platelet-lymphocyte ratios and coronary artery calcification score among asymptomatic patients: data from a cross-sectional study. Mediators of inflammation, 2019. 2019.
30. Chen, T., H. Chen, H. Xiao, H. Tang, Z. Xiang, X. Wang, et al., Comparison of the Value of Neutrophil to High-Density Lipoprotein Cholesterol Ratio and Lymphocyte to High-Density Lipoprotein Cholesterol Ratio for Predicting Metabolic Syndrome Among a Population in the Southern Coast of China. Diabetes Metab Syndr Obes, 2020. 13: p. 597-605.
31. Surendar, J., K. Indulekha, V. Mohan, and R. Pradeepa, Association of neutrophil-lymphocyte ratio with metabolic syndrome and its components in Asian Indians (CURES-143). Journal of Diabetes and its Complications, 2016. 30(8): p. 1525-1529.
32. Yilmaz, H., B. Ucan, M. Sayki, I. Unsal, M. Sahin, M. Ozbek, et al., Usefulness of the neutrophil-to-lymphocyte ratio to prediction of type 2 diabetes mellitus in morbid obesity. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 2015. 9(4): p. 299-304.
33. Nima Taghizadeh , S.M., Vahid Saeedi, Ladan Haghighi, Mona Nourbakhsh, Mitra Nourbakhsh, Maryam Razzaghy Azar, Association between Steroid Hormones and Insulin Resistance in Patients with Polycystic Ovary Syndrome. Acta Biochimnica Iranica, 2023. 1(1): p. 26-31.
34. Yang, L., S. Liu, J. Liu, Z. Zhang, X. Wan, B. Huang, et al., COVID-19: immunopathogenesis and Immunotherapeutics. Signal transduction and targeted therapy, 2020. 5(1): p. 128.
35. He, R., Z. Lu, L. Zhang, T. Fan, R. Xiong, X. Shen, et al., The clinical course and its correlated immune status in COVID-19 pneumonia. Journal of Clinical Virology, 2020. 127: p. 104361.
36. Lu, G. and J. Wang, Dynamic changes in routine blood parameters of a severe COVID-19 case. Clinica Chimica Acta, 2020. 508: p. 98-102.
37. Soraya, G.V. and Z.S. Ulhaq, Crucial laboratory parameters in COVID-19 diagnosis and prognosis: An updated meta-analysis. Medicina Clínica, 2020. 155(4): p. 143-151.
38. Henry, B., I. Cheruiyot, J. Vikse, V. Mutua, V. Kipkorir, J. Benoit, et al., Lymphopenia and neutrophilia at admission predicts severity and mortality in patients with COVID-19: a meta-analysis. Acta Biomed, 2020. 91(3): p. e2020008.
39. Oliveira, D.C.d., B.S. Spiri, Y.C. Schluga, J.L.P. Justus, F.D.N. Lopes Neto, and A.P.d. Azambuja, Evaluation of lymphocyte count, T-cell subsets and neutrophil-to-lymphocyte ratio as early predictors for severity and outcome of COVID-19 disease–a report from a highly complex hospital in Brazil. Hematology, Transfusion and Cell Therapy, 2023. 45(3): p. 330-337.
40. Golucci, A.P.B.S., F.A.L. Marson, A.F. Ribeiro, and R.J.N. Nogueira, Lipid profile associated with the systemic inflammatory response syndrome and sepsis in critically ill patients. Nutrition, 2018. 55: p. 7-14.
41. Catapano, A.L., A. Pirillo, F. Bonacina, and G.D. Norata, HDL in innate and adaptive immunity. Cardiovascular research, 2014. 103(3): p. 372-383.
42. Murphy, A.J., K.J. Woollard, A. Suhartoyo, R.A. Stirzaker, J. Shaw, D. Sviridov, et al., Neutrophil activation is attenuated by high-density lipoprotein and apolipoprotein AI in in vitro and in vivo models of inflammation. Arteriosclerosis, thrombosis, and vascular biology, 2011. 31(6): p. 1333-1341.
43. Wang, S.-h., S.-g. Yuan, D.-q. Peng, and S.-p. Zhao, HDL and ApoA-I inhibit antigen presentation-mediated T cell activation by disrupting lipid rafts in antigen presenting cells. Atherosclerosis, 2012. 225(1): p. 105-114.
44. Tall, A.R. and L. Yvan-Charvet, Cholesterol, inflammation and innate immunity. Nature Reviews Immunology, 2015. 15(2): p. 104-116.
45. Argun, D., F. Argun, P. Basim, and M. Bayraktaroglu, Monocyte-to-High-Density Lipoprotein Cholesterol Ratio: a Candidate Parameter for a Risk Assessment Model in COVID-19. Clin Lab, 2022. 68(3).
46. Kou, T., H. Luo, and L. Yin, Relationship between neutrophils to HDL-C ratio and severity of coronary stenosis. BMC Cardiovascular Disorders, 2021. 21: p. 1-8.
47. Xie, J., Y. Zu, A. Alkhatib, T.T. Pham, F. Gill, A. Jang, et al., Metabolic syndrome and COVID-19 mortality among adult black patients in New Orleans. Diabetes care, 2021. 44(1): p. 188-193.
48. Adab, P., S. Haroon, M.E. O’Hara, and R.E. Jordan, Comorbidities and covid-19. 2022, British Medical Journal Publishing Group.
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| Issue | Vol 1 No 3 (2023) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/abi.v1i3.14549 | |
| Keywords | ||
| COVID-19 Neutrophil to HDL-C Ratio Monocyte to HDL-C Ratio Lymphocyte to HDL-C Ratio CBC WBC | ||
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How to Cite
1.
Hosseini H, Rohani-Rasaf M, Vatannejad A, kheirollahi A, Shabani M, Teimouri M. Assessment of leukocyte subtypes to high-density lipoprotein-cholesterol (HDL-C) ratios as predictors of severity and mortality in COVID-19 patients. ABI. 2023;1(3):133-138.
