Original Article
 

Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality

Abstract

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers.
Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated.
Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%.
Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.

1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33.
2. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265-9.
3. Contini C, Di Nuzzo M, Barp N, Bonazza A, De Giorgio R, Tognon M, et al. The novel zoonotic COVID-19 pandemic: An expected global health concern. J Infect Dev Ctries. 2020;14(3):254-64.
4. Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, et al. Multiorgan and Renal Tropism of SARS-CoV-2. N Engl J Med. 2020;383(6):590-2.
5. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475-81.
6. Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol. 2020;11:1446.
7. 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(10223):507-13.
8. 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(10223):497-506.
9. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846-8.
10. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62.
11. World Health O. Clinical management of COVID-19: interim guidance, 27 May 2020. Geneva: World Health Organization; 2020 2020. Contract No.: WHO/2019-nCoV/clinical/2020.5.
12. Gebhard C, Regitz-Zagrosek V, Neuhauser HK, Morgan R, Klein SL. Impact of sex and gender on COVID-19 outcomes in Europe. Biol Sex Differ. 2020;11(1):29.
13. Jin J-M, Bai P, He W, Wu F, Liu X-F, Han D-M, et al. Gender Differences in Patients With COVID-19: Focus on Severity and Mortality. Frontiers in public health. 2020;8:152-.
14. Bonanad C, García-Blas S, Tarazona-Santabalbina F, Sanchis J, Bertomeu-González V, Fácila L, et al. The Effect of Age on Mortality in Patients With COVID-19: A Meta-Analysis With 611,583 Subjects. J Am Med Dir Assoc. 2020;21(7):915-8.
15. Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106(16):2067-72.
16. Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nature Reviews Immunology. 2020;20(6):355-62.
17. Jing Liang J, Liu J, Chen Y, Ye B, Li N, Wang X, et al. Characteristics of laboratory findings of COVID-19 patients with comorbid diabetes mellitus. Diabetes research and clinical practice. 2020;167:108351-.
18. Braga TT, Forni MF, Correa-Costa M, Ramos RN, Barbuto JA, Branco P, et al. Soluble Uric Acid Activates the NLRP3 Inflammasome. Scientific reports. 2017;7:39884-.
19. Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091.
20. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97(5):829-38.
21. Li Z, Wu M, Yao J, Guo J, Liao X, Song S, et al. Caution on Kidney Dysfunctions of COVID-19 Patients. medRxiv. 2020:2020.02.08.20021212.
22. Henry BM, Lippi G. Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection. International urology and nephrology. 2020;52(6):1193-4.
23. Xue X, Ma J, Zhao Y, Zhao A, Liu X, Guo W, et al. Correlation between hypophosphatemia and the severity of Corona Virus Disease 2019 patients. medRxiv. 2020:2020.03.27.20040816.
24. Fan Z, Chen L, Li J, Cheng X, Yang J, Tian C, et al. Clinical Features of COVID-19-Related Liver Functional Abnormality. Clin Gastroenterol Hepatol. 2020;18(7):1561-6.
25. Wang Y, Shi L, Wang Y, Duan G, Yang H. Albumin and total bilirubin for severity and mortality in coronavirus disease 2019 patients. J Clin Lab Anal. 2020;34(7):e23412.
26. Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003;348(20):1986-94.
27. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A, et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis. 2013;13(9):752-61.
28. Wu MY, Yao L, Wang Y, Zhu XY, Wang XF, Tang PJ, et al. Clinical evaluation of potential usefulness of serum lactate dehydrogenase (LDH) in 2019 novel coronavirus (COVID-19) pneumonia. Respir Res. 2020;21(1):171.
29. Ali N. Elevated level of C-reactive protein may be an early marker to predict risk for severity of COVID-19. J Med Virol. 2020;92(11):2409-11.
30. Liu T, Zhang J, Yang Y, Ma H, Li Z, Zhang J, et al. The role of interleukin-6 in monitoring severe case of coronavirus disease 2019. EMBO Mol Med. 2020;12(7):e12421.
31. Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Frontiers in immunology. 2018;9:754-.
32. Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 2014;6(4):748-73.
33. Rosário C, Zandman-Goddard G, Meyron-Holtz EG, D'Cruz DP, Shoenfeld Y. The hyperferritinemic syndrome: macrophage activation syndrome, Still's disease, septic shock and catastrophic antiphospholipid syndrome. BMC medicine. 2013;11:185-.
34. Huang I, Pranata R, Lim MA, Oehadian A, Alisjahbana B. C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis. Therapeutic advances in respiratory disease. 2020;14:1753466620937175-.
35. Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018;9:754.
36. Leggett BA, Brown NN, Bryant SJ, Duplock L, Powell LW, Halliday JW. Factors affecting the concentrations of ferritin in serum in a healthy Australian population. Clin Chem. 1990;36(7):1350-5.
37. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2020;39(5):405-7.
38. Rostamian A, Ghazanfari T, Arabkheradmand J, Edalatifard M, Ghaffarpour S, Salehi MR, et al. Interleukin-6 as a Potential Predictor of COVID-19 Disease Severity in Hospitalized Patients and its Association with Clinical Laboratory Routine Tests. Immunoregulation. 2020;3(1):29-36.
39. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-4.
40. Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1(2):135-45.
41. de Jonge E, Friederich PW, Vlasuk GP, Rote WE, Vroom MB, Levi M, et al. Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects. Clinical and diagnostic laboratory immunology. 2003;10(3):495-7.
42. Marin V, Montero-Julian FA, Grès S, Boulay V, Bongrand P, Farnarier C, et al. The IL-6-soluble IL-6Ralpha autocrine loop of endothelial activation as an intermediate between acute and chronic inflammation: an experimental model involving thrombin. J Immunol. 2001;167(6):3435-42.
43. Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity. 1997;6(3):315-25.
44. Steensberg A, Fischer CP, Keller C, Møller K, Pedersen BK. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab. 2003;285(2):E433-7.
45. Kuppalli K, Rasmussen AL. A glimpse into the eye of the COVID-19 cytokine storm. EBioMedicine. 2020;55.
46. Pimentel GD, Dela Vega MCM, Laviano A. High neutrophil to lymphocyte ratio as a prognostic marker in COVID-19 patients. Clinical nutrition ESPEN. 2020;40:101-2.
47. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. National Science Review. 2020;7(6):998-1002.
48. Xie G, Ding F, Han L, Yin D, Lu H, Zhang M. The role of peripheral blood eosinophil counts in COVID-19 patients. Allergy. 2020.
49. Wang C, Deng R, Gou L, Fu Z, Zhang X, Shao F, et al. Preliminary study to identify severe from moderate cases of COVID-19 using combined hematology parameters. Ann Transl Med. 2020;8(9):593.
50. Khartabil TA, Russcher H, van der Ven A, de Rijke YB. A summary of the diagnostic and prognostic value of hemocytometry markers in COVID-19 patients. Crit Rev Clin Lab Sci. 2020;57(6):415-31.
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IssueVol 20 No 1 (2021) QRcode
SectionOriginal Article(s)
Published2021-02-11
DOI https://doi.org/10.18502/ijaai.v20i1.5412
Keywords
Biomarkers COVID-19 Immunology Inflammation SARS-CoV-2

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1.
Ghazanfari T, Salehi MR, Namaki S, Arabkheradmand J, Rostamian A, Rajabnia Chenary M, Ghaffarpour S, Kaboudanian Ardestani S, Edalatifard M, Naghizadeh MM, Mohammadi S, Mahloujirad M, Izadi A, Ghanaati H, Beigmohammadi MT, Vodjgani M, Mohammad Shirazi B, Mirsharif ES, Abdollahi A, Mohammadi M, Emadi Kouchak H, Dehghan Manshadi SA, Zamani MS, Mahmoodi Aliabadi M, Jamali D, Khajavirad N, Mohseni Majd AM, Nasiri Z, Faghihzadeh S. Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality. Iran J Allergy Asthma Immunol. 20(1):46-66.