Correlations and Algorithmization of Cytokine Status Analysis of Patients with Coronary Heart Disease in the Early Recovery Period After COVID-19

The purpose of research is study of correlations and algorithmization of cytokine status analysis of patients with coronary heart disease in the early recovery period after COVID-19.

Methods. Cytokine status was studied in 40 patients with coronary heart disease 3-4 weeks after recovery from COVID19. The control consisted of 38 patients with coronary heart disease without COVID-19. The level of cytokines in the blood was determined on the device "Becton Dickinson FACS Canto 2 (USA)". Correlation and regression analysis were used in statistical analysis.

Results. Reliable moderate correlations were established between IL-6 and IL-2, IL-3, respectively, r = 0,35 and r = 0,33; IL-17 with IL-2 and IL-6 – r = 0,28 and r = 0,63, respectively; TNF-α and IFN-γ with IL-6 – r = 0,42 and r = 0,39. At the same time, the greatest association, according to the values of the correlation coefficients, among the studied interleukins in patients with coronary heart disease during the convalescence period is characteristic of IL-6. However, IL-17 also had a significant number of correlations with the cytokines under consideration. All this indicates a high association of IL-6, IL-17 and IFN-γ with other cytokines during the recovery period of patients with coronary heart disease after COVID-19 and their priority participation in the development and recovery of these patients. To identify the most informative blood cytokines, an algorithm for analyzing the cytokine status has been developed, which provides for the development of uncorrected and adjusted mathematical models by gender and age of patients with coronary heart disease who have undergone COVID-19. It was found that the greatest effect on recovery 3-4 weeks after COVID-19 in patients with coronary heart disease has the level of IL-17 in the blood (OR = 1,792, p = 0,0021) in an uncorrected and adjusted by gender and age model (OR = 1,708, p = 0,0012).

Conclusion. The established correlations, algorithms and models created are proposed to be used in assessing the
dynamics of recovery of patients with coronary heart disease after COVID-19.

1. Nicola M., Alsafi Z., Sohrabi C., Kerwan A., Al-Jabir A., Iosifidis C., Agha M., Agha R. The Socio-Economic Implications of the Coronavirus Pandemic (COVID-19): A Review. Int. J. Surg, 2020, no. 78, pp. 185–193. https://doi.org/10.1016/j.ijsu.2020.04.018

2. Chang W. T., Toh H. S., Liao C. T., Yu W. L. Cardiac Involvement of COVID-19: A Comprehensive Review. Am. J. Med. Sci., 2021, no. 361, pp. 14–22. https://doi.org/ 10.1016/j.amjms.2020.10.002

3. Xie Y., Xu E., Bowe B., Al-Aly Z. Long-Term Cardiovascular Outcomes of COVID-19. Nat. Med., 2022, no. 28, pp. 583–590. https://doi.org/10.1038/s41591-022-01689-3

4. Zhang L., Feng X., Zhang D., Jiang C., Mei H., Wang J., Zhang C., Li H., Xia X., Kong S., eds. Deep Vein Thrombosis in Hospitalized Patients With COVID-19 in Wuhan, China: Prevalence, Risk Factors, and Outcome. Circulation, 2020, no. 142, pp. 114–128. https://doi.org/10.1161/CIRCULATIONAHA.120.046702

5. Delli M. N., Finocchi F., Tossetta G., Salvio G., Cutini M., Marzioni D., Balercia G. Could SARS-CoV-2 Infection Affect Male Fertility and Sexuality? APMIS, 2022, no. 130, pp. 243–252. https://doi.org/10.1111/apm.13210

6. Tessitore E., Carballo D., Poncet A., Perrin N., Follonier C., Assouline B., Carballo S., Girardin F., Mach F. Mortality and High Risk of Major Adverse Events in Patients with COVID-19 and History of Cardiovascular Disease. Open Heart, 2021, no. 8, p. e001526. https://doi.org/10.1136/openhrt-2020-001526

7. Ye Q., Wang B., Mao J. The Pathogenesis and Treatment of the Cytokine Storm in COVID-19. J. Infect, 2020, no. 80, pp. 607–613. https://doi.org/10.1016/j.jinf.2020.03.037

8. Bénard A., Jacobsen A., Brunner M., Krautz C., Klösch B., Swierzy I., Naschberger E., Podolska M. J., Kouhestani D., David P., et al. Interleukin-3 Is a Predictive Marker for Severity and Outcome during SARS-CoV-2 Infections. Nat. Commun, 2021, no. 12, pp. 1112. https://doi.org/10.1038/s41467-021-21310-4

9. Gurko T. S., Agarkov N. M., Lev I. V., Korovin E. N., Leon H. F. Osobennosti postural'nyh narushenij i svyazej s sistemoj komplementa krovi pri sindrom padenij u pozhilyh [Features of postural disorders and connections with the blood complement system in falls syndrome in the elderly]. Nauchnye rezul'taty biomedicinskih issledovanij = Research Results in Biomedicine, 2022, vol. 8, no. 2, pp. 259–267. https://doi.org/10.18413/ 2658-6533-2022-8-2- 0-10

10. McGonagle D., Sharif K., O’Regan A., Bridgewood C. The Role of Cytokines Including Interleukin-6 in COVID-19 Induced Pneumonia and Macrophage Activation SyndromeLike Disease. Autoimmun. Rev., 2020, no. 19, pp. 102537. https://doi.org/10.1016/ j.autrev.2020.102537

11. Salama C., Han J., Yau L., Reiss W. G., Kramer B., Neidhart J. D., Criner G. J., Kaplan-Lewis E., Baden R., Pandit L., eds. Tocilizumab in Patients Hospitalized with COVID-19 Pneumonia. N. Engl. J. Med., 2021, no. 384, pp. 20–30. https://doi.org/10.1056/NEJMoa 2030340

12. Law C. C., Puranik R., Fan J., Fei J., Hambly B. D., Bao S. Clinical Implications of IL-32, IL-34 and IL-37 in Atherosclerosis: Speculative Role in Cardiovascular Manifestations of COVID-19. Front. Cardiovasc. Med., 2021, no. 8, p. 630767. https://doi.org/ 10.3389/fcvm.2021.630767

13. Kashiwagi M., Ozaki Y., Imanishi T., Taruya A., Kuroi A., Katayama Y., Shimamura K., Shiono Y., Tanimoto T., Kubo T. Interleukin-34 Levels Are Increased in Acute Myocardial Infarction and Associated with Major Adverse Cardiovascular Events. Coron. Artery Dis, 2022, no. 31, pp. 61–63. https://doi.org/10.1097/MCA.0000000000001046

14. Bergantini L., d’Alessandro M., Cameli P., Otranto A., Luzzi S., Bianchi F., Bargagli E. Cytokine Profiles in the Detection of Severe Lung Involvement in Hospitalized Patients with COVID-19: The IL-8/IL-32 Axis. Cytokine, 2022, no. 151, p. 155804. https://doi.org/ 10.1016/ j.cyto.2022.155804

15. Kaufmann C. C., Ahmed A., Burger A. L., Muthspiel M., Jäger B., Wojta J., Huber K. Biomarkers Associated with Cardiovascular Disease in COVID-19. Cells, 2022, no. 11, p. 922. https://doi.org/10.3390/cells11060922

16. Yang Z., Shi L., Xue Y., Zeng T., Shi Y., Lin Y., Liu L. Interleukin-32 Increases in Coronary Arteries and Plasma from Patients with Coronary Artery Disease. Clin. Chim. Acta, 2019, no. 497, pp. 104–109. https://doi.org/10.1016/j.cca.2019.07.019

17. Di Benedetto P., Guggino G., Manzi G., Ruscitti P., Berardicurti O., Panzera N., Grazia N., Badagliacca R., Riccieri V., Vizza C. D., eds. Interleukin-32 in Systemic Sclerosis, a Potential New Biomarker for Pulmonary Arterial Hypertension. Arthritis Res. Ther., 2020, no. 22, p. 127. https://doi.org/10.1186/s13075-020-02218-8

18. Oldroyd K. G., Rush C. J., Berry C. Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction. JAMA Cardiol., 2021, no. 6(10), pp. 1130–1143. https://doi.org/10.1001/jamacardio. 2021. 1825

19. Clarke R., Valses-Marquez E., Hill M. Plasma cytokines and risk of coronary heart disease in the PROCARDIS study. Open Heart, 2018, no. 5(1), p. е000807. https://doi.org/ 10.1136/openhrt-2018-000807

20. Yang L., Wang L., Deng Y. Serum lipids profiling perturbances in patients with ischemic heart disease and ischemic cardiomyopathy. Lipids Health Dis., 2020, no. 19(1), p. 89. https://doi.org/10.1186/s12944-020-01269-9