FACTORS ASSOCIATED WITH VARIABILITY IN IL-6 LEVELS IN PATIENTS WITH COVID-19
DOI:
https://doi.org/10.11603/1681-2727.2023.2.14097Keywords:
COVID-19, interleukin-6, comorbidity, age characteristicsAbstract
SUMMARY. An increase in the systemic level of IL-6 in patients with COVID-19 is considered as a relevant parameter for predicting the most severe course of the disease and the need for intensive therapy. We conducted a study of the level of interleukin-6 in 77 patients with coronavirus disease aged from 29 to 87 years (mean age 59.3±12.4 years), among whom there were men – 43 (55.8 %), women – 34 (44.2 %). The examination was carried out the next day after hospitalization. On average, the period from the onset of the disease was (9.2±3.5) days. According to the results of the study, it was established that the average level of IL-6 among patients with COVID-19 significantly exceeded the similar indicator in relatively healthy individuals: Me – 5.30 (3.57; 11.32) pg/l against 2.68 (2,22; 2.97) (p<0.001).
Analysis of IL-6 content depending on demographic, clinical and general laboratory characteristics showed that its increase in blood serum correlates with age (rs=0.251, p=0.030), and the highest average level of this cytokine was observed in the age group of 70–79 years (rs=0.381, p=0.001). among the clinical characteristics, the correlation of the level of IL-6 with the severe course of the disease was determined (rs=0.381, p=0.001), which corresponds to the role of this cytokine as a possible marker of the progression of the severe course of the disease. Accordingly, there is also a tendency to link the fatal outcome of the disease with an increase in the level of IL-6 (rs=0.210, p=0.071), which may have a reliable result with a larger number of observations. Among the general laboratory indicators, a direct correlation was observed between the level of IL-6 and the ESR value (rs=0.271, p=0.019), the number of bands (rs=0.301, p=0.009), residual nitrogen (rs=0.231, p=0.047), the content of CRP (rs=0.241, p=0.037), which, like IL-6, is an important marker of the acute phase of inflammation, and high levels of this protein in the early stage of coronavirus disease are positively correlated with the degree of lung damage and the severity of the disease. Thus, as a result of the conducted study, it was established that the increase in the level of interleukin-6, which is observed in patients with COVID-19 is correlated with the severity of the disease and may also be related to age (especially the age group of 70–79 years) and a number of concomitant pathology and clinical conditions, among which coronary heart disease, obesity, fever, increased BP (systolic), decreased saturation are especially important. Higher levels of interleukin-6 are observed with an increase in the content of C-reactive protein, residual nitrogen, ESR, and the number of bands.
References
McGonagle, D., Sharif, K., O’Regan, A., & Bridgewood, C. (2020). The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmunity Reviews, 19 (6), 102537. Available from https://doi.org/10.1016/j.autrev.2020.102537 DOI: https://doi.org/10.1016/j.autrev.2020.102537
Wang, Y., & Perlman, S. (2022). COVID-19: inflammatory profile. Annual review of medicine, 73, 65-80. Available from: https://doi.org/10.1146/annurev-med-042220-012417 DOI: https://doi.org/10.1146/annurev-med-042220-012417
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. Available from: https://doi.org/10.1016/S2213-2600(20)30076-X DOI: https://doi.org/10.1016/S2213-2600(20)30076-X
Vatansever, H. S., & Becer, E. (2020). Relationship between IL-6 and COVID-19: to be considered during treatment. Future Virology, 15(12), 817-822. Available from: https://doi.org/10.2217/fvl-2020-0168 DOI: https://doi.org/10.2217/fvl-2020-0168
Fattori, E., Cappelletti, M., Costa, P., Sellitto, C., Cantoni, L., Carelli, M., ... & Poli, V. (1994). Defective inflammatory response in interleukin 6-deficient mice. The Journal of Experimental Medicine, 180 (4), 1243-1250. https://doi.org/10.1084/jem.180.4.1243. DOI: https://doi.org/10.1084/jem.180.4.1243
Otsuka, R., & Seino, K.I. (2020). Macrophage activation syndrome and COVID-19. Inflammation and regeneration, 40, 1-6. Available from: https://doi.org/10.1186/s41232-020-00131-w DOI: https://doi.org/10.1186/s41232-020-00131-w
Stüber, F., Wrigge, H., Schroeder, S., Wetegrove, S., Zinserling, J., Hoeft, A., & Putensen, C. (2002). Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury. Intensive Care Medicine, 28, 834-841. https://doi.org/10.1007/s00134-002-1321-7 DOI: https://doi.org/10.1007/s00134-002-1321-7
Parsons, P. E., Eisner, M. D., Thompson, B. T., Matthay, M. A., Ancukiewicz, M., Bernard, G. R., ... & NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network. (2005). Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Critical Care Medicine, 33 (1), 1-6. https://doi.org/10.1097/01.ccm.0000149854.61192.dc DOI: https://doi.org/10.1097/01.CCM.0000149854.61192.DC
McElvaney, O. J., Curley, G. F., Rose-John, S., & McElvaney, N. G. (2021). Interleukin-6: obstacles to targeting a complex cytokine in critical illness. The Lancet Respiratory Medicine, 9(6), 643-654. https://doi.org/10.1016/S2213-2600(21)00103-X DOI: https://doi.org/10.1016/S2213-2600(21)00103-X
Halim, C., Mirza, A. F., & Sari, M. I. (2022). The association between TNF-α, IL-6, and vitamin D levels and COVID-19 severity and mortality: a systematic review and meta-analysis. Pathogens, 11 (2), 195. Available from: https://doi.org/10.3390/pathogens11020195 DOI: https://doi.org/10.3390/pathogens11020195
Tian, W., Jiang, W., Yao, J., Nicholson, C. J., Li, R. H., Sigurslid, H. H., ... & Malhotra, R. (2020). Predictors of mortality in hospitalized COVID-19 patients: a systematic review and meta-analysis. Journal of medical virology, 92(10), 1875-1883. Available from: https://doi.org/10.1002/jmv.26050 DOI: https://doi.org/10.1002/jmv.26050
Sanyaolu, A., Okorie, C., Marinkovic, A., Patidar, R., Younis, K., Desai, P., ... & Altaf, M. (2020). Comorbidity and its impact on patients with COVID-19. SN comprehensive clinical medicine, 2, 1069-1076. Available from: https://doi.org/10.1007/s42399-020-00363-4
Bilokon, O. O., & Lytvyn, K. Yu. (2023). Analysis of clinical and laboratory characteristics of COVID-19 in elderly patients. Bilokon, O. O., & Lytvyn, K. Yu. (2023). Analysis of clinical and laboratory characteristics of COVID-19 in elderly patients. Infectious Diseases, 3, 12–17. https://doi.org/10.11603/1681-2727.2022.3.13472 [in Ukrainian] DOI: https://doi.org/10.11603/1681-2727.2022.3.13472
Sanyaolu, A., Okorie, C., Marinkovic, A., Patidar, R., Younis, K., Desai, P., ... & Altaf, M. (2020). Comorbidity and its impact on patients with COVID-19. SN Comprehensive Clinical Medicine, 2, 1069-1076. Available from: https://doi.org/10.1007/s42399-020-00363-4 DOI: https://doi.org/10.1007/s42399-020-00363-4
Meftahi, G. H., Jangravi, Z., Sahraei, H., & Bahari, Z. (2020). The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of “inflame-aging”. Inflammation Research, 69, 825-839. https://doi.org/10.1007/s00011-020-01372-8 DOI: https://doi.org/10.1007/s00011-020-01372-8
Gubernatorova, E. O., Gorshkova, E. A., Polinova, A. I., & Drutskaya, M. S. (2020). IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine & Growth Factor Reviews, 53, 13-24. https://doi.org/10.1016/j.cytogfr.2020.05.009
Antomonov, M. Yu. (2018). Mathematical processing and analysis of medical and biological data. 2nd edition. Kyiv: MIT Medinform [in Ukrainian].
Gubernatorova, E. O., Gorshkova, E. A., Polinova, A. I., & Drutskaya, M. S. (2020). IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine & Growth Faactor Reviews, 53, 13-24. https://doi.org/10.1016/j.cytogfr.2020.05.009 DOI: https://doi.org/10.1016/j.cytogfr.2020.05.009
Hotamisligil, G. S. (2006). Inflammation and metabolic disorders. Nature, 444 (7121), 860-867. https://doi.org/10.1038/nature05485 DOI: https://doi.org/10.1038/nature05485
Chae, C. U., Lee, R. T., Rifai, N., & Ridker, P. M. (2001). Blood pressure and inflammation in apparently healthy men. Hypertension, 38 (3), 399-403. https://doi.org/10.1161/01.hyp.38.3.399 DOI: https://doi.org/10.1161/01.HYP.38.3.399
Akbari, M., & Hassan-Zadeh, V. (2018). IL-6 signalling pathways and the development of type 2 diabetes. Inflammopharmacology, 26, 685-698. https://doi.org/10.1007/s10787-018-0458-0 DOI: https://doi.org/10.1007/s10787-018-0458-0
Wang, L. (2020). C-reactive protein levels in the early stage of COVID-19. Medecine et maladies infectieuses, 50 (4), 332-334. https://doi.org/10.1016/j.medmal.2020.03.007 DOI: https://doi.org/10.1016/j.medmal.2020.03.007
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. https://doi.org/10.1016/j.it.2020.10.012 DOI: https://doi.org/10.1016/j.it.2020.10.012
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 K. Yu. Lytvyn, O. O. Bilokon
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Journal Infectious Disease (Infektsiini Khvoroby) allows the author(s) to hold the copyright without registration
Users can use, reuse and build upon the material published in the journal but only for non-commercial purposes
This journal is available through Creative Commons (CC) License BY-NC "Attribution-NonCommercial" 4.0
