Effect of Cytokines Gene Expression and Serum Level of Vitamin D on the Severity of COVID-19

Kazempour Dizaji, Mehdi; Jamaati, Hamidreza; Bahrami, Naghmeh; Farzanegan, Behrooz; Rekabi, Mahsa; Mokhber Dezfuli, Mogtaba; Heshmat Nia, Jalal; Madani, Mohammadreza; Daustani, Mahya; Shirian, Sadegh; Masoumi, Ladan; Ghaemi, Amir; Narimani, Armita; Khakbaz, Mehran; Mohamadnia, Abdolreza; Varahram, Mohammad; Velayati, Ali Akbar

doi:10.30699/ijmm.16.5.412

year 16, Issue 5 (September - October 2022) Iran J Med Microbiol 2022, 16(5): 412-419 | Back to browse issues page

‎ 10.30699/ijmm.16.5.412

Mendeley

Zotero

RefWorks

Kazempour Dizaji M, Jamaati H, Bahrami N, Farzanegan B, Rekabi M, Mokhber Dezfuli M, et al et al . Effect of Cytokines Gene Expression and Serum Level of Vitamin D on the Severity of COVID-19. Iran J Med Microbiol 2022; 16 (5) :412-419
URL: http://ijmm.ir/article-1-1812-en.html

Effect of Cytokines Gene Expression and Serum Level of Vitamin D on the Severity of COVID-19

Mehdi Kazempour Dizaji¹

, Hamidreza Jamaati²

, Naghmeh Bahrami³

, Behrooz Farzanegan⁴

, Mahsa Rekabi⁵

, Mogtaba Mokhber Dezfuli⁶

, Jalal Heshmat Nia²

, Mohammadreza Madani²

, Mahya Daustani⁷

, Sadegh Shirian⁸

, Ladan Masoumi⁹

, Amir Ghaemi¹⁰

, Armita Narimani¹¹

, Mehran Khakbaz¹¹

, Abdolreza Mohamadnia

¹², Mohammad Varahram¹³

, Ali Akbar Velayati¹³

1- Biostatistics Department, Mycobacteriology Research Center, National Research Institute of Tuberculosis and lung Diseases, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
3- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
4- Critical Care Quality Improvement Research Center at Shahid Modarres Hospital, Department of Anesthesiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5- Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis & Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
6- Lung transplantation Research Center, National Research Institute of Tuberculosis, and lung Diseases, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
7- Department of Biotechnology, Faculty of Sciences, Islamic Azad University, Tehran, Iran
8- Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran
9- Shefa Khatam Neuroscience Research Center, Tehran, Iran
10- Department of Virology, Pasture Institute, Tehran, Iran
11- Department of Cell and Molecular Biology, School of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
12- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran , mohamadnia.ar@gmail.com
13- Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract: (2053 Views)

Background and Aim: The COVID-19 disease is an emerging infectious disease that appeared in December 2019 in Wuhan, China. An uncontrolled systemic inflammatory response is one of the primary mechanisms causing death in this disease. In this study, the expression levels of some inflammatory cytokines, vitamin D, and some hematological and biochemical parameters were compared in patients with severe COVID-19 and mild types.
Materials and Methods: In this cross-sectional study, 60 blood samples were taken from 30 severe coronavirus patients and 30 mild coronavirus patients. The expression levels of cytokines such as IL (interleukin)-6, interferon (IFN)-α, IL-12, transforming growth factor (TGF) β, IL-8 and tumor necrosis factor (TNF)-α were evaluated using Real-time PCR. A T-test was used for Statistical Analysis.
Results: IL-6, IFN-α, IL-12, TGF-β, IL-8, and TNF-α cytokines in the peripheral blood of severe patients, were positive in 28/30 (93.33%), 27/30 (90%), 24/30 (80%), 25/30 (83.33%), 26/30 (86.66%), and 27/30 (90%) respectively. The positive rate of these cytokines in the mild patients were 20/30 (66.67%), 21/30 (70%), 18/30 (60%), 17/30 (56.67%), 19/30 (63.33%), 18/30 (60%), respectively. There was a statistically significant difference between these two groups in terms of cytokines biomarkers. A significant difference was found between both groups in terms of the serum level of lactate dehydrogenase (LDH), the mean number of lymphocytes and neutrophils as well as the mean percentage of neutrophils/ lymphocytes ratio (NLR).
Conclusion: The expression of cytokine genes and their release into the peripheral blood was increased in both severe and mild patients with COVID-19. However, they were more intense in patients with severe symptoms than those with mild symptoms and can cause inflammatory and even destructive reactions. Vitamin D deficiency plays no role in causing severe COVID-19 in patients without risk factors. Severe COVID-19 is characterized by elevated serum levels of LDH and NLR≥3.45.

Keywords: severe COVID-19, Mild COVID-19, ARDS, Cytokine expression

Full-Text [PDF 584 kb] (464 Downloads) | | Full-Text (HTML) (670 Views)

Type of Study: Original Research Article | Subject: Medical Virology
Received: 2022/07/1 | Accepted: 2022/07/17 | ePublished: 2022/08/8

References

1. Lamb LE, Bartolone SN, Ward E, Chancellor MB. Rapid Detection of Novel Coronavirus (COVID19) by Reverse Transcription-Loop-Mediated Isothermal Amplification. MedRxiv. 2020. [DOI:10.2139/ssrn.3539654]

2. Shi Z, Hu Z. A review of studies on animal reservoirs of the SARS coronavirus. Virus Res. 2008;133(1): 74-87. [DOI:10.1016/j.virusres.2007.03.012] [PMID] [PMCID]

3. Dariushnejad H, Ghorbanzadeh V, Akbari S, Hashemzadeh P. Designing a Multi-epitope Peptide Vaccine Against COVID-19 Variants Utilizing In-silico Tools. Iran J Med Microbiol. 2021; 15(5):592-605. [DOI:10.30699/ijmm.15.5.592]

4. Abdollahi A, Mahmoudi-Aliabadi M, Mehrtash V, Jafarzadeh B, Salehi M. The novel coronavirus SARS-CoV-2 vulnerability association with ABO/Rh blood types. Iran J Pathol. 2020;15(3):156-60. [DOI:10.30699/ijp.2020.125135.2367] [PMID] [PMCID]

5. De Wit E, Van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016;14(8):523-4. [DOI:10.1038/nrmicro.2016.81] [PMID] [PMCID]

6. 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. [DOI:10.1016/S0140-6736(20)30183-5]

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. [DOI:10.1016/S0140-6736(20)30211-7]

8. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. [DOI:10.1001/jama.2020.1585] [PMID] [PMCID]

9. Hui RK, Zeng F, Chan CM, Yuen K, Peiris JS, Leung FC. Reverse transcriptase PCR diagnostic assay for the coronavirus associated with severe acute respiratory syndrome. J Clin Microbiol. 2004;42 (5):1994-9. [DOI:10.1128/JCM.42.5.1994-1999.2004] [PMID] [PMCID]

10. Peiris M, Guan Y, Yuen K. Severe acute respiratory syndrome: Wiley Online Library; 2005. [DOI:10.1002/9780470755952]

11. Williams AE, Chambers RC. The mercurial nature of neutrophils: still an enigma in ARDS?. Am J Physiol Lung Cell Mol Physiol. 2014;306(3):L217-L30. [DOI:10.1152/ajplung.00311.2013] [PMID] [PMCID]

12. Min C-K, Cheon S, Ha N-Y, Sohn KM, Kim Y, Aigerim A, et al. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity. Sci Rep. 2016;6(1):1-12. [DOI:10.1038/srep25359] [PMID] [PMCID]

13. To KK-W, Tsang OT-Y, Yip CC-Y, Chan K-H, Wu T-C, Chan JM-C, et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis. 2020; 71(15):841-3. [DOI:10.1093/cid/ciaa149] [PMID] [PMCID]

14. Heydar H, Mansouri K, Norooznezhad M, Norooznezhad F, Mohamadnia A, Bahrami N. Bevacizumab Inhibits Angiogenic Cytokines in Head and Neck Squamous Cell Carcinoma: From Gene to the Protein. Int J Hematol-Oncol Stem Cell Res. 2018;12(2):136-41.

15. Karimi S, Bahrami N, Sharifi K, Daustany M, Baghbani-Arani F, Kazempour M, et al. Investigating gene expression level of MUC1 and CEA in pleural fluid of NSCLC lung cancer patients with real-time RT-PCR method. Minerva Pneumol. 2017;56(1):18-24. [DOI:10.23736/S0026-4954.16.01772-7]

16. Bahrami N, Gholami M, Jamaati HR, Mohamadnia A, Dargahi H, Kazempour Dizaji M, et al. Expression of two essential mRNA biomarker in the peripheral blood as possible biomarkers for diagnosis of non-small cell lung carcinoma. Minerva Pneumol. 2016;55(3):31-6.

17. Ghadimi K, Bahrami N, Fathi M, Farzanegan B, Naji T, Emami M, et al. Diagnostic value of LunX mRNA and CEA mRNA expression in pleural fluid of patients with non-small cell lung cancer. Minerva Pneumol. 2017;56(2):90-5. [DOI:10.23736/S0026-4954.16.01773-9]

18. Farzanegan B, Bahrami N, Birjandi B, Khosravi A, Nasab AF, Fathi M, et al. Down-Expression of miRNA-98 and Over-Expression of miRNA-9 Can Result in Inadequate Immune System Response against Lung Cancer. Biointerface Res Appl Chem. 2021;11(6):13893-902. [DOI:10.33263/BRIAC116.1389313902]

19. Bolandparva F, Nasab MSH, Mohamadnia A, Garajei A, Nasab AF, Bahrami N. Early Diagnosis of Oral Squamous Cell Carcinoma (OSCC) by miR-138 and miR-424-5p Expression as a Cancer Marker. Asian Pac J Cancer Prev. 2021;22(7):2185-9. [DOI:10.31557/APJCP.2021.22.7.2185] [PMID] [PMCID]

20. Ozaki K, Leonard WJ. Cytokine and Cytokine Receptor Pleiotropy and Redundancy. J Biol Chem. 2002;277(33):29355-8. [DOI:10.1074/jbc.R200003200] [PMID]

21. Dinarello CA. Historical insights into cytokines. Eur J Immunol. 2007;37(S1):S34-S45. [DOI:10.1002/eji.200737772] [PMID] [PMCID]

22. Scarpioni R, Ricardi M, Albertazzi V. Secondary amyloidosis in autoinflammatory diseases and the role of inflammation in renal damage. World J Nephrol. 2016;5(1):66-75. [DOI:10.5527/wjn.v5.i1.66] [PMID] [PMCID]

23. Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest. 2000;117(4):1162-72. [DOI:10.1378/chest.117.4.1162] [PMID]

24. Zinchuk A, Holubovska O, Shkurba A, Hrytsko R, Vorozhbyt O, Richniak M, et al. Original inhibition method of excessive synthesis of pro-inflammatory cytokine of tumour necrosis factor α. Central-Eur J Immunol. 2015;40(3):345-8. [DOI:10.5114/ceji.2015.54597] [PMID] [PMCID]

25. Arend WP. The mode of action of cytokine inhibitors. J Rheumatol Suppl. 2002;65:16-21.

26. Shaikh PZ. Cytokines & their physiologic and pharmacologic functions in inflammation: A review. Int J Pharm & Life Sci. 2011;2(11):1274-63.

27. Zhang Y, Li J, Zhan Y, Wu L, Yu X, Zhang W, et al. Analysis of Serum Cytokines in Patients with Severe Acute Respiratory Syndrome. Infect Immun. 2004;72(8):4410-5. [DOI:10.1128/IAI.72.8.4410-4415.2004] [PMID] [PMCID]

28. De Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TNB, et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med. 2006;12 (10):1203-7. [DOI:10.1038/nm1477] [PMID] [PMCID]

29. Cillóniz C, Shinya K, Peng X, Korth MJ, Proll SC, Aicher LD, et al. Lethal Influenza Virus Infection in Macaques Is Associated with Early Dysregulation of Inflammatory Related Genes. PLoS Pathog. 2009;5(10):e1000604. [DOI:10.1371/journal.ppat.1000604] [PMID] [PMCID]

30. Tavakoli-Ardakani M, Abbaspour H, Nasab AF, Meibodi AM, Kheradmand A. Study of the Effect of Memantine on Negative Sign in Patients with Schizophrenia and Schizoaffective Disorders. Iran J Pharma Res. 2018;17(Suppl):122-9.

31. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529-39. Springer: Berlin Heidelberg. [DOI:10.1007/s00281-017-0629-x] [PMID] [PMCID]

32. Teijaro JR. Cytokine storms in infectious diseases. Semin Immunopathol; 2017;39(5):501-3. Springer: Berlin Heidelberg. [DOI:10.1007/s00281-017-0640-2] [PMID] [PMCID]

33. Xi-zhi JG, Thomas PG. New fronts emerge in the influenza cytokine storm. Semin Immunopathol. 2017;39(5):541-50. Springer: Berlin Heidelberg. [DOI:10.1007/s00281-017-0636-y] [PMID] [PMCID]

34. Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, et al. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe. 2016;19(2):181-93. [DOI:10.1016/j.chom.2016.01.007] [PMID] [PMCID]

35. Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nat Rev Immunol. 2013;13(12):875-87. [DOI:10.1038/nri3547] [PMID] [PMCID]

36. Davidson S, Maini MK, Wack A. Disease-Promoting Effects of Type I Interferons in Viral, Bacterial, and Coinfections. J Interferon Cytokine Res. 2015;35 (4):252-64. [DOI:10.1089/jir.2014.0227] [PMID] [PMCID]

37. Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10(2):102-8. [DOI:10.1016/j.jpha.2020.03.001] [PMID] [PMCID]

38. Cheng OZ, Palaniyar N. NET balancing: a problem in inflammatory lung diseases. Front Immunol. 2013;4:1. [DOI:10.3389/fimmu.2013.00001]

39. 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. [DOI:10.1038/s41586-020-2008-3] [PMID] [PMCID]

40. Alosaimi B, Hamed ME, Naeem A, Alsharef AA, AlQahtani SY, AlDosari KM, et al. MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/ chemokines and elevated inflammatory innate immune response in the lower respiratory tract. Cytokine. 2020;126:154895. [DOI:10.1016/j.cyto.2019.154895] [PMID] [PMCID]

41. Lau SK, Lau CC, Chan K-H, Li CP, Chen H, Jin D-Y, et al. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. J Gen Virol. 2013;94 (12):2679-90. [DOI:10.1099/vir.0.055533-0] [PMID]