The effect of circulating cytokines on cardiovascular patients infected with the Coronavirus

Main Article Content

Ruqaya Yahya Abd AL-Shaheed
Huda Jameel Baker AL-Khilkhali


patients, infected, coronavirus


The coronavirus illness (COVID-19) is caused by serious acute respiratory disorder coronavirus 2 (SARS-CoV-2), moreover known as the COVID-19 virus. After the first-ever reports of COVID-19 in December 2019, the malady spread quickly. In January 2020, the WHO announced the outbreak a Public Health Emergency of Worldwide Concern, and by March 2020, the WHO characterized the episode as a global widespread . The current study aimed to detect the effect of SARS-CoV-2 infection in heart patients and study their immune response by detecting the levels of some cytokines, which may end in a cytokine storm and may lead to death. In this study, one hundred-eight subjects were enrolled on two comparison case-control groups, the case group included 54 patients suffering from SARS-COV2, all were selected from those who were admitted to the Intensive Care Unit (ICU), and were diagnosed by a specialist physician with severe acute respiratory syndrome due to SARS-COV2 documented by Real-Time Polymerase Chain Reaction( RT-PCR ) besides other clinical and laboratory criteria in Marjan Medical City in Babylon province, AL-Amal Hospital for Communicable Diseases and AL-Hakeem Hospital, Najaf/Iraq , for a period from March 2022 to October 2022 to evaluate the role of some selected serological among patients with SARA-COV2 .
The control group in this study included 54 subjects, divided into three groups (Apparent Healthy, patients suffered from SARS-COV2, patients suffered from CVD). Blood samples were examined through immunological methods, and an enzyme-linked immunosorbent assay (ELISA) was adopted for the detection of the concentration of TNF-α, IL6, IL-10,1L-12 and CCL2 .The immunological evaluation to clarify the theory of cytokines storm carried in the present study revealed that (TNF-α, IL6, IL-10,1L-12, and CCL2) for patients with COVID-19 and CVD was significantly higher than all the comparison group . The study reported that interleukin (6, 10, 12) and TNF-a are significantly increased in patients with covid19, CVD, and COVID-19 patients only, compared to healthy people. furthermore, IL-6 and IL-12 levels increased in patients with CVD only when compared to healthy people. There is a significant increase in CCL2 in all study groups compared to healthy people who have lower levels and this study indicated that the infection with Covid disease was severe and critical in most patients with CVD. This increased the number of deaths among them.

Abstract 107 | PDF Downloads 132


1. Barna BP, Pettay J, Barnett GH, Zhou P, Iwasaki K, Estes ML. Regulation of Monocyte Chemoattractant Protein-1 Expression in Adult Human Non-Neoplastic Astrocytes Is Sensitive to Tumor Necrosis Factor (Tnf) or Antibody to the 55-Kda Tnf Receptor. J Neuroimmunol (1994) 50(1):101–7.
2. Bradley, J. (2008). TNF‐mediated inflammatory disease. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland, 214(2), 149–160.
3. Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., ... & Zhang, L. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet, 395(10223), 507-513.
4. Costela-Ruiz, V. J., Illescas-Montes, R., Puerta-Puerta, J. M., Ruiz, C., & Melguizo-Rodríguez, L. (2020). SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine & Growth Factor Reviews, 54, 62–75.
5. Gajovic, N., Markovic, S. S., Jurisevic, M., Jovanovic, M., Arsenijevic, N., Mijailovic, Z., Jovanovic, M., & Jovanovic, I. (2023). Galectin-3 is an important prognostic marker for COVID-19 severity. Scientific Reports, 13(1), 1460.
6. Giamarellos-Bourboulis, E. J., Netea, M. G., Rovina, N., Akinosoglou, K., Antoniadou, A., Antonakos, N., Damoraki, G., Gkavogianni, T., Adami, M.-E., & Katsaounou, P. (2020). Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host & Microbe, 27(6), 992–1000.
7. Gram M, Sveinsdottir S, Cinthio M, Sveinsdottir K, Hansson SR, Morgelin M,et al. Extracellular Hemoglobin - Mediator of Inflammation and CellDeath in the Choroid Plexus Following Preterm Intraventricular Hemorrhage. J Neuroinflamm (2014) 11:200. doi: 10.1186/s12974-014-0200-9.
8. Han H, MaQ, Li C, Liu R, Zhao L, WangW, et al. Profiling SerumCytokines in Covid-19 Patients Reveals Il-6 and Il-10 Are Disease Severity Predictors. Emerg Microbes Infect (2020) 9(1):1123–30.
9. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
10. Hansson, G. K. (2005). Inflammation, atherosclerosis, and coronary artery disease. New England Journal of Medicine, 352(16), 1685–1695.
11. Hopkins, J. (2020). Johns Hopkins coronavirus resource centre COVID- 19 Case Tracker.
12. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497–506.
13. Hussein, H. A. M. (2021). Correlation of CCL2, CCL5 and CXCL10 Chemokines with Disease Severity among Patients with COVID-19 Infection. Ministry of Higher Education.
14. Islam, H., Chamberlain, T. C., Mui, A. L., & Little, J. P. (2021). Elevated interleukin-10 levels in COVID-19: potentiation of pro-inflammatory responses or impaired anti-inflammatory action? Frontiers in Immunology, 12, 677008.
15. IuI, R., Cherniavskiĭ, A. M., IaV, P., Volkov, A. M., Kashtanova, E. V, SIu, T., & Polovnikova, E. M. (2012). Inflammatory-destructive biomarkers of atherosclerotic plaque instability. Study of arterial wall and blood. Kardiologiia, 52(5), 37–41.
16. Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM.(2001). The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J; 15: 43–58.
17. Khailany, R.A., Safdar, M., and Ozaslan, M. (2020) Genomic characterization of a novel SARS-CoV-2. Gene reports, 19:100682
18. Kim, I.-C., Song, J. E., Lee, H. J., Park, J.-H., Hyun, M., Lee, J. Y., Kim, H. A., Kwon, Y. S., Park, J. S., & Youn, J.-C. (2020). The implication of cardiac injury score on in-hospital mortality of coronavirus disease 2019. Journal of Korean Medical Science, 35(39).
19. Liu Y, Chen D, Hou J, Li H, Cao D, Guo M, et al.. An inter-correlated cytokine network identified at the centre of the cytokine storm predicted COVID-19 prognosis. Cytokine. (2021) 138:155365. 10.1016/j.cyto.2020.155365
20. Libby, P. (2001). Current concepts of the pathogenesis of acute coronary syndromes. Circulation, 104(3), 365–372.
21. Lu, L., Zhang, H., Dauphars, D. J., & He, Y.-W. (2021). A potential role of interleukin 10 in COVID-19 pathogenesis. Trends in Immunology, 42(1), 3–5.
22. Lubrano, V., & Balzan, S. (2020). Cardiovascular risk in COVID-19 infection. American Journal of Cardiovascular Disease, 10(4), 284.
23. Lubrano, V., Cocci, F., Battaglia, D., Papa, A., Marraccini, P., & Zucchelli, G. C. (2005). The usefulness of high‐sensitivity IL‐6 measurement for clinical characterization of patients with coronary artery disease. Journal of Clinical Laboratory Analysis, 19(3), 110–114.
24. Ma, L., Song, K., & Huang, Y. (2021). Coronavirus disease-2019 (COVID-19) and cardiovascular complications. Journal of Cardiothoracic and Vascular Anesthesia, 35(6), 1860–1865.
25. McDermott, D. H., Yang, Q., Kathiresan, S., Cupples, L. A., Massaro, J. M., Keaney Jr, J. F., Larson, M. G., Vasan, R. S., Hirschhorn, J. N., & O’Donnell, C. J. (2005). CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study. Circulation, 112(8), 1113–1120.
26. Montazersaheb, S., Hosseiniyan Khatibi, S. M., Hejazi, M. S., Tarhriz, V., Farjami, A., Ghasemian Sorbeni, F., Farahzadi, R., & Ghasemnejad, T. (2022). COVID-19 infection: An overview on cytokine storm and related interventions. Virology Journal, 19(1), 1–15.
27. Mokhtari, T., Hassani, F., Ghaffari, N., Ebrahimi, B., Yarahmadi, A., & Hassanzadeh, G. (2020). COVID-19 and multiorgan failure: A narrative review on potential mechanisms. Journal of Molecular Histology, 51, 613–628.
28. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A.(2001). Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001, 19:683-765.
29. Nguyen, N., Nguyen, H., Ukoha, C., Hoang, L., Patel, C., Ikram, F. G., Acharya, P., Dhillon, A., & Sidhu, M. (2022). Relation of interleukin-6 levels in COVID-19 patients with major adverse cardiac events. Baylor University Medical Center Proceedings, 35(1), 6–9.
30. Patterson, C. C., Smith, A. E., Yarnell, J. W. G., Rumley, A., Ben-Shlomo, Y., & Lowe, G. D. O. (2010). The associations of interleukin-6 (IL-6) and downstream inflammatory markers with risk of cardiovascular disease: the Caerphilly Study. Atherosclerosis, 209(2), 551–557.
31. Ranjbar, M., Rahimi, A., Baghernejadan, Z., Ghorbani, A., & Khorramdelazad, H. (2022). Role of CCL2/CCR2 axis in the pathogenesis of COVID-19 and Possible Treatments: All options on the Table. International Immunopharmacology, 113, 109325.
32. Riley, E., Dasari, V., Frishman, W. H., & Sperber, K. (2008). Vaccines in development to prevent and treat atherosclerotic disease. Cardiology in Review, 16(6), 288–300.
33. Shechter, M., Shechter, A., Koren-Morag, N., Feinberg, M. S., & Hiersch, L. (2014). The usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease. The American Journal of Cardiology, 113(1), 162–167.
34. Song, Y., Gao, P., Ran, T., Qian, H., Guo, F., Chang, L., Wu, W., & Zhang, S. (2020). High inflammatory burden: a potential cause of myocardial injury in critically ill patients with COVID-19. Frontiers in Cardiovascular Medicine, 7, 128.
35. Tabrez, S., Ali, M., Jabir, N. R., Firoz, C. K., Ashraf, G. M., Hindawi, S., Damanhouri, G. A., & Nabil Alama, M. (2017). A putative association of interleukin‐10 promoter polymorphisms with cardiovascular disease. Iubmb Life, 69(7), 522–527.
36. Tang, Y., Liu, J., Zhang, D., Xu, Z., Ji, J., & Wen, C. (2020). Cytokine storm in COVID-19: the current evidence and treatment strategies. Frontiers in Immunology, 11, 1708.
37. Trinchieri G.(1995). Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol. ;13:251-276.
38. Van der Heijden, T., Bot, I., & Kuiper, J. (2019). The IL-12 cytokine family in cardiovascular diseases. Cytokine, 122, 154188.
39. Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., ... & Wang, F. S. (2020). Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet respiratory medicine, 8(4), 420-422.
40. Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., & Gu, X. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet, 395(10229), 1054–1062.
41. Zlotnik, A., & Yoshie, O. (2012). The chemokine superfamily revisited. Immunity, 36(5), 705–716.