Author(s):
Mohammed H. Taleb, Eman K. Syam, Ihab M. Almasri, Mariam Hassan, Mahmoud M. Tawfick
Email(s):
almataleb21@gmail.com , emakha233@gmail.com , ihabalmasri@yahoo.com , mariam.hassan@pharma.cu.edu.eg , mahmoud_tawfick@azhar.edu.eg
DOI:
10.52711/0974-360X.2024.00640 
Address:
Mohammed H. Taleb1, Eman K. Syam1, Ihab M. Almasri2, Mariam Hassan3,4, Mahmoud M. Tawfick5,6*
1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University-Gaza, Gaza 79702, Palestine.
2Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Gaza 79702, Palestine.
3Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
4Department of Microbiology and Immunology, Faculty of Pharmacy, Galala University, New Galala City, Suez, Egypt.
5Department of Microbiology and Immunology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
6Department of Microbiology and Immunology, Faculty of Pharmacy (For Boys), Al-Azhar University, Cairo 11751, Egypt.
*Corresponding Author
Published In:
Volume - 17,
Issue - 9,
Year - 2024
ABSTRACT:
Diabetes mellitus (DM) is a risk factor for severe coronavirus disease 2019 (COVID-19) and even death. This study assessed the blood levels of immune-inflammatory and other biomarkers in severe COVID-19 diabetic patients and identified possible predictive biomarkers for disease severity. The cross-sectional study was conducted in a tertiary hospital in Gaza from 15 February 2022 to 15 July 2022. The study patients were in three Groups (each group 14 patients): ICU severe COVID-19 diabetic patients (Group 1), non-hospitalized non-diabetic patients with mild/moderate COVID-19 (Group 2) and non-COVID-19 diabetic patients (Group 3). The evaluated blood biomarkers and statistically analyzed were CRP, LDH, PCT, Ang-II, IL-6, ferritin, ESR (immune-inflammatory biomarkers), D-dimer (coagulative biomarker), CK-MB and cTn I (cardiac biomarkers), AST, ALT (liver biomarkers), HbA1c, RBC, HGB, WBC and LYM (hematologic biomarkers). ICU diabetic patients (Group 1) had the highest average age. Group 1 patients had significantly more elevated CRP, LDH, PCT, AngII, Ferritin, IL-6 and ESR, D-dimer and CK-MB levels than the other two groups at P< 0.05. Group 2 patients showed higher levels than Group 3 patients. Haematological biomarkers, except WBC, were higher among patients in Group 3 than in the other two groups. There was no significant difference between the three patient groups regarding AST and ALT levels. The study results showed a high association between LDH, PCT, Ang II, ferritin, IL-6, CK-MB, cTn I, D-dimer and LYM levels and the severity of COVID-19 in diabetic patients. These findings support the notion that DM can lead to the rapid progression of COVID-19 and make it more prone to an inflammatory cytokine storm and cardiac and coagulation problems, which could lead to various organ failures and a bad prognosis of COVID-19.
Cite this article:
Mohammed H. Taleb, Eman K. Syam, Ihab M. Almasri, Mariam Hassan, Mahmoud M. Tawfick. Evaluation of Immune-Inflammatory and Other Biomarkers in Severe COVID-19 Patients with Diabetes Mellitus: A Cross-Sectional Study. Research Journal of Pharmacy and Technology. 2024; 17(9):4131-1. doi: 10.52711/0974-360X.2024.00640
Cite(Electronic):
Mohammed H. Taleb, Eman K. Syam, Ihab M. Almasri, Mariam Hassan, Mahmoud M. Tawfick. Evaluation of Immune-Inflammatory and Other Biomarkers in Severe COVID-19 Patients with Diabetes Mellitus: A Cross-Sectional Study. Research Journal of Pharmacy and Technology. 2024; 17(9):4131-1. doi: 10.52711/0974-360X.2024.00640 Available on: https://rjptonline.org/AbstractView.aspx?PID=2024-17-9-1
REFERENCES:
1. World Health Organization (WHO) Virtual press conference on COVID-19 (2022). Accessed September 1 2022. https://www.who.int/europe/emergencies/situations/covid-19.
2. Stokes EK, Zambrano LD, Anderson KN, et al. Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020. MMWR Morb Mortal Wkly Rep. 2020; 69(24): 759-765. Published 2020; Jun 19. doi:10.15585/mmwr.mm6924e2
3. Rokade M, Khandagale P. Coronavirus disease: A review of a new threat to public health. Asian J. Pharm. Res. 2020; 10(3): 241-244. doi:10.5958/2231-5691.2020.00042.8
4. Pavithra D, Praveen D, Aanandhi MV. A Comprehensive review on Biomarkers for assessing Diabetic Kidney Disease. Research J. Pharm. and Tech. 2017; 10(9): 3242-3246. doi:10.5958/0974-360X.2017.00575.3
5. Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci. 2020; 57(6): 389-399.
6. Mehta P, McAuley DF, Brown M, et al. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395(10229): 1033-1034. doi:10.1016/S0140-6736(20)30628-0
7. Stebbing J, Phelan A, Griffin I, et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020; 20(4): 400-402. doi:10.1016/S1473-3099(20)30132-8
8. Yadam N, Suhasin G. Prediction of COVID-19 severity associated with Pneumonia by chest CT scan and Serological results. Asian J. Pharm. Tech.. 2021; 11(3): 198-202. doi:10.52711/2231-5713.2021.00032
9. Wang J, Jiang M, Chen X, Montaner LJ. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol. 2020; 108(1): 17-41. doi:10.1002/JLB.3COVR0520-272R
10. Gao Y, Li T, Han M, et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol. 2020; 92(7): 791-796. doi:10.1002/jmv.25770
11. Qin JJ, Cheng X, Zhou F, et al. Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19. Hypertension. 2020; 76(4): 1104-1112. doi:10.1161/HYPERTENSIONAHA.120.15528
12. Chen L, Liu HG, Liu W, et al. Zhonghua Jie He He Hu Xi Za Zhi. = Chinese journal of tuberculosis and respiratory diseases. 2020; 43(3): 203-208. doi:10.3760/cma.j.issn.1001-0939.2020.03.013
13. Zhang Y, Zheng L, Liu L, Zhao M, Xiao J, Zhao Q. Liver impairment in COVID-19 patients: A retrospective analysis of 115 cases from a single centre in Wuhan City, China. Liver Int. 2020; 40(9): 2095-2103. doi:10.1111/liv.14455
14. Kaur H. Effectiveness of structured teaching programme regarding self care management in relation to prevention of complications among diabetics. Asian J Nur Edu Res. 2014; 4(3): 279-283.
15. Kumar P, Mangalathil TX, Choudhary V. An experimental study to assess the effectiveness of structured teaching programme on knowledge regarding the management of diabetes mellitus among GNM students in selected nursing school at Sikar, Rajasthan. Asian J. Management. 2014; 5(3): 329-331.
16. Lim S, Bae JH, Kwon HS, Nauck MA. COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat Rev Endocrinol. 2021; 17(1): 11-30. doi:10.1038/s41574-020-00435-4
17. Panari H, Vegunarani M. Study on complications of diabetes mellitus among the diabetic patients. Asian J Nur Edu Res. 2016; 6(2): 171-182. doi:10.5958/2349-2996.2016.00032.X
18. Kulcsar KA, Coleman CM, Beck SE, Frieman MB. Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection. JCI Insight. 2019; 4(20): e131774. Published 2019 Oct 17. doi:10.1172/jci.insight.131774
19. Song W, Gui M, Wang X, Xiang Y. Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog. 2018; 14(8): e1007236. doi:10.1371/journal.ppat.1007236
20. Coopersmith CM, Antonelli M, Bauer SR, et al. The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease 2019 in Critical Illness. Crit Care Med. 2021; 49(4): 598-622. doi:10.1097/CCM.0000000000004895
21. Gregg EW, Sophiea MK, Weldegiorgis M. Diabetes and COVID-19: Population Impact 18 Months Into the Pandemic. Diabetes Care. 2021; 44(9): 1916-1923. doi:10.2337/dci21-0001
22. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study [published correction appears in Lancet. 2020; Mar 28; 395(10229):1038] [published correction appears in Lancet. 2020; Mar 28; 395(10229):1038]. Lancet. 2020; 395(10229): 1054-1062. doi:10.1016/S0140-6736(20)30566-3
23. Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020; 8(6): 546-550. doi:10.1016/S2213-8587(20)30152-2
24. Koh H, Moh AMC, Yeoh E, et al. Diabetes predicts severity of COVID-19 infection in a retrospective cohort: A mediatory role of the inflammatory biomarker C-reactive protein. J Med Virol. 2021; 93(5): 3023-3032. doi:10.1002/jmv.26837
25. Sahu P, Pinkalwar N, Dubey RD, Paroha S, Chatterjee S, Chatterjee T. Biomarkers: an emerging tool for diagnosis of a disease and drug development. Asian J. Res. Pharm. Sci. 2011; 1(1): 9-16.
26. Halmaciu I, Arbănași EM, Kaller R, et al. Chest CT Severity Score and Systemic Inflammatory Biomarkers as Predictors of the Need for Invasive Mechanical Ventilation and of COVID-19 Patients' Mortality. Diagnostics (Basel). 2022; 12(9): 2089. Published 2022; Aug 29. doi:10.3390/diagnostics12092089
27. Mazaheri T, Ranasinghe R, Al-Hasani W, et al. A cytokine panel and procalcitonin in COVID-19, a comparison between intensive care and non-intensive care patients. PLoS One. 2022; 17(5): e0266652. Published 2022; May 2. doi:10.1371/journal.pone.0266652
28. Wan S, Yi Q, Fan S, et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). MedRxiv. Published February 12, 2020,20021832. doi:10.1101/2020.02.10.20021832.
29. Martha JW, Wibowo A, Pranata R. Prognostic value of elevated lactate dehydrogenase in patients with COVID-19: a systematic review and meta-analysis. Postgrad Med J. 2022; 98(1160): 422-427. doi:10.1136/postgradmedj-2020-139542
30. Perpiñan C, Bertran L, Terra X, et al. Predictive Biomarkers of COVID-19 Severity in SARS-CoV-2 Infected Patients with Obesity and Metabolic Syndrome. J Pers Med. 2021; 11(3): 227. Published 2021; Mar 22. doi:10.3390/jpm11030227
31. Leisman DE, Ronner L, Pinotti R, et al. Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. Lancet Respir Med. 2020; 8(12): 1233-1244. doi:10.1016/S2213-2600(20)30404-5
32. Camporota L, Chiumello D, Busana M, Gattinoni L, Marini JJ. Pathophysiology of COVID-19-associated acute respiratory distress syndrome. Lancet Respir Med. 2021; 9(1): e1. doi:10.1016/S2213-2600(20)30505-1
33. Patel T, George P. Serum procalcitonin: a novel biomarker in st-segment elevation myocardial infarction to predict in-hospital and 30 days outcomes. J Am Coll Cardiol. 2016; 67(13S): 503. doi:10.1016/S0735-1097(16)30504-6
34. Tong-Minh K, van der Does Y, Engelen S, et al. High procalcitonin levels associated with increased intensive care unit admission and mortality in patients with a COVID-19 infection in the emergency department. BMC Infect Dis. 2022; 22(1): 165. Published. 2022; Feb 21. doi:10.1186/s12879-022-07144-5
35. Kaal A, Snel L, Dane M, et al. Diagnostic yield of bacteriological tests and predictors of severe outcome in adult patients with COVID-19 presenting to the emergency department. Emerg Med J. 2021; 38(9): 685-691. doi:10.1136/emermed-2020-211027
36. Janc J, Suchański M, Mierzchała-Pasierb M, Woźnica-Niesobska E, Łysenko L, Leśnik P. Does the Serum Concentration of Angiotensin II Type 1 Receptor Have an Effect on the Severity of COVID-19? A Prospective Preliminary Observational Study among Healthcare Professionals. J Clin Med. 2022; 11(7): 1769. Published 2022 Mar 23. doi:10.3390/jcm11071769
37. Nicola W, Sidhom G, El Khyat Z, Ibrahim S, Salah A, El Sayed A. Plasma angiotensin II, renin activity and serum angiotensin-converting enzyme activity in non-insulin dependent diabetes mellitus patients with diabetic nephropathy. Endocr J. 2001; 48(1): 25-31. doi:10.1507/endocrj.48.25
38. Guzzi PH, Mercatelli D, Ceraolo C, Giorgi FM. Master Regulator Analysis of the SARS-CoV-2/Human Interactome. J Clin Med. 2020; 9(4): 982. Published 2020 Apr 1. doi:10.3390/jcm9040982
39. Lalueza A, Ayuso B, Arrieta E, et al. Elevation of serum ferritin levels for predicting a poor outcome in hospitalized patients with influenza infection. Clin Microbiol Infect. 2020; 26(11): 1557.e9-1557.e15. doi:10.1016/j.cmi.2020.02.018
40. 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. Ther Adv Respir Dis. 2020; 14: 1753466620937175. doi:10.1177/1753466620937175
41. Malik SUF, Chowdhury PA, Hakim A, Islam MS, Alam MJ, Azad AK. Blood biochemical parameters for assessment of COVID-19 in diabetic and non-diabetic subjects: a cross-sectional study. Int J Environ Health Res. 2022; 32(6): 1344-1358. doi:10.1080/09603123.2021.1879741
42. Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018;9:754. Published 2018; Apr 13. doi:10.3389/fimmu.2018.00754
43. Pairazaman AT, Tipian JM, Mamani OA, et al. Erythrocyte sedimentation rate in COVID-19 patients treated at the CLAS health center, Nuevo Lurín, 2021. F1000 Research. 2022; 11(1278): 1278. A waiting peer review. https://f1000research.com/articles/11-1278
44. Zinellu A, Sotgia S, Fois AG, Mangoni AA. Serum CK-MB, COVID-19 severity and mortality: An updated systematic review and meta-analysis with meta-regression. Adv Med Sci. 2021; 66(2): 304-314. doi:10.1016/j.advms.2021.07.001
45. Dhivya K, Samuel GG. Prognostic potential of serum biomarkers as predictors for cardiovascular complications and disease progression in chronic kidney disease patients. Research J. Pharm. and Tech. 2016; 9(3): 227-234. doi: 10.5958/0974-360X.2016.00041.X
46. Shah P, Doshi R, Chenna A, et al. Prognostic Value of Elevated Cardiac Troponin I in Hospitalized Covid-19 Patients. Am J Cardiol. 2020;135:150-153. doi:10.1016/j.amjcard.2020.08.041
47. Li JW, Han TW, Woodward M, et al. The impact of 2019 novel coronavirus on heart injury: A Systematic review and Meta-analysis. Prog Cardiovasc Dis. 2020; 63(4): 518-524. doi:10.1016/j.pcad.2020.04.008
48. Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail. 2020; 26(6): 470-475. doi:10.1016/j.cardfail.2020.04.009
49. Auditeau C, Khider L, Planquette B, Sanchez O, Smadja DM, Gendron N. D-dimer testing in clinical practice in the era of COVID-19. Res Pract Thromb Haemost. 2022; 6(4): e12730. Published 2022; May 25. doi:10.1002/rth2.12730
50. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 18(4): 844-847. doi:10.1111/jth.14768
51. Mishra Y, Pathak BK, Mohakuda SS, et al. Relation of D-dimer levels of COVID-19 patients with diabetes mellitus. Diabetes Metab Syndr. 2020; 14(6): 1927-1930. doi:10.1016/j.dsx.2020.09.035
52. Hamid ZA, Al-Bayaa YJ, Hussain AH. Hepatitis B surface antigen level and its correlation with age, gender, and liver biomarkers. Research J. Pharm. and Tech. 2021; 14(8): 4207-42011. doi: 10.52711/0974-360X.2021.00729
53. Tokarczyk U, Kaliszewski K, Kopszak A, et al. Liver Function Tests in COVID-19: Assessment of the Actual Prognostic Value. J Clin Med. 2022; 11(15): 4490. Published 2022; Aug 1. doi:10.3390/jcm11154490
54. Zhang Y, Zheng L, Liu L, Zhao M, Xiao J, Zhao Q. Liver impairment in COVID-19 patients: A retrospective analysis of 115 cases from a single centre in Wuhan city, China. Liver Int. 2020; 40(9): 2095-2103. doi:10.1111/liv.14455
55. Grace JA, Herath CB, Mak KY, Burrell LM, Angus PW. Update on new aspects of the renin-angiotensin system in liver disease: clinical implications and new therapeutic options. Clin Sci (Lond). 2012; 123(4): 225-239. doi:10.1042/CS20120030
56. Azghar A, Bensalah M, Berhili A, et al. Value of hematological parameters for predicting patients with severe coronavirus disease 2019: a real-world cohort from Morocco. J Int Med Res. 2022;50(7):3000605221109381. doi:10.1177/03000605221109381
57. Tan L, Wang Q, Zhang D, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study [published correction appears in Signal Transduct Target Ther. 2020 Apr 29;5(1):61]. Signal Transduct Target Ther. 2020; 5(1): 33. Published 2020 Mar 27. doi:10.1038/s41392-020-0148-4
58. Zhao Q, Meng M, Kumar R, et al. Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A systemic review and meta-analysis. Int J Infect Dis. 2020; 96: 131-135. doi:10.1016/j.ijid.2020.04.086
59. Russo A, Tellone E, Barreca D, Ficarra S, Laganà G. Implication of COVID-19 on Erythrocytes Functionality: Red Blood Cell Biochemical Implications and Morpho-Functional Aspects. Int J Mol Sci. 2022; 23(4): 2171. Published 2022 Feb 16. doi:10.3390/ijms23042171
60. Tao Z, Xu J, Chen W, et al. Anemia is associated with severe illness in COVID-19: A retrospective cohort study. J Med Virol. 2021; 93(3): 1478-1488. doi:10.1002/jmv.26444
61. Benoit JL, Benoit SW, de Oliveira MHS, Lippi G, Henry BM. Anemia and COVID-19: A prospective perspective. J Med Virol. 2021; 93(2): 708-711. doi:10.1002/jmv.26530
62. Kermali M, Khalsa RK, Pillai K, Ismail Z, Harky A. The role of biomarkers in diagnosis of COVID-19 - A systematic review. Life Sci. 2020; 254: 117788. doi:10.1016/j.lfs.2020.117788
63. Williamson EJ, Walker AJ, Bhaskaran K, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020; 584(7821): 430-436. doi:10.1038/s41586-020-2521-4
64. Alkundi A, Mahmoud I, Musa A, Naveed S, Alshawwaf M. Clinical characteristics and outcomes of COVID-19 hospitalized patients with diabetes in the United Kingdom: A retrospective single centre study. Diabetes Res Clin Pract. 2020; 165: 108263. doi:10.1016/j.diabres.2020.108263
65. Agarwal S, Schechter C, Southern W, Crandall JP, Tomer Y. Preadmission Diabetes-Specific Risk Factors for Mortality in Hospitalized Patients with Diabetes and Coronavirus Disease 2019. Diabetes Care. 2020; 43(10): 2339-2344. doi:10.2337/dc20-1543