Dynamic changes of cytokines in COVID-19 and in the post-COVID period

封面

如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

Cytokines play a key role in the pathogenesis of COVID-19 and its complications. The course of this infection is characterized by a hyperactive immune response known as a “cytokine storm”, which can lead to significant tissue and organ damage.

The aim: to study the dynamics of interleukins (IL) levels in patients with COVID-19, with a primary focus on immune responses during acute infection and their association with severity of the disease and post-COVID consequences.

Material and methods. Using multiplex analysis, IL levels were studied in 294 patients with varying degrees of COVID-19 severity.

Results. It was found that in the acute phase of COVID-19, the levels of IL-1α, IL-1β and IL-2 were increased, and the level of IL-1β in severe cases was noticeably reduced. Concentration of IL-7 was increased in patients with severe cases of the disease, while IL-8 remained reduced during the acute phase. Changes in IL-10 concentrations were different in groups of patients with different degrees of COVID-19 severity. IL-2 levels positively correlated with arterial hypertension, and IL-7 levels had a negative correlation with this disease. IL-10 and IL-8 levels correlated negatively with the presence of Omicron strain, but positively with Delta strain. Also, the concentrations of these cytokines positively correlated with severe cases of COVID-19 and negatively with mild ones.

Conclusion. Increased levels of anti-inflammatory ILs in the acute phase of COVID-19 may indicate an enhanced inflammatory response, while changes in anti-inflammatory ILs may indicate regulatory mechanisms aimed at mitigating inflammation. In the post-COVID period, patients may develop complications such as arterial hypertension and type 2 diabetes mellitus, each of which is associated with unique cytokine profiles. Understanding the ILs’ dynamics expands our understanding of COVID-19 pathogenesis and may improve the development of precision medical interventions to improve patients’ outcomes.

全文:

受限制的访问

作者简介

Karakoz Mussabay

Astana Medical University

编辑信件的主要联系方式.
Email: mussabay.k@amu.kz
ORCID iD: 0000-0001-7440-4014

MD, Master of Biological Sciences, senior lecturer at the Department of microbiology and virology named after Sh.I. Sarbasov

哈萨克斯坦, Astana

Elizaveta Vinogradova

Nazarbayev University

Email: st.paulmississippi@gmail.com
ORCID iD: 0009-0003-1845-2726

MD, Master, senior researcher at the Department of microbiome of Center for Life Sciences of National Laboratory

哈萨克斯坦, Astana

Marat Dusmagambetov

Astana Medical University

Email: dusmagambetov.m@amu.kz
ORCID iD: 0000-0003-2395-6032
哈萨克斯坦, Astana

Makhabbat Bekbosynova

Heart Center

Email: cardiacsurgeryres@gmail.com
ORCID iD: 0000-0003-2834-617X

MD, Dr. Sci. (Medicine), cardiologist of the highest category, deputy chairman of the board

哈萨克斯坦, Astana

Ainur Tauekelova

Heart Center

Email: tauekelovaajnura@gmail.com
哈萨克斯坦, Astana

Samat Kozhakhmetov

Nazarbayev University

Email: skozhakhmetov@nu.edu.kz
ORCID iD: 0000-0001-9668-0327

MD, PhD (Biology), associate professor, senior researcher at the Department of microbiome of Life Sciences Center of National Laboratory

哈萨克斯坦, Astana

Almagul Kushugulova

Nazarbayev University

Email: akushugulova@nu.edu.kz
ORCID iD: 0000-0001-9479-0899

MD., Dr. Sci. (Medicine), professor, head of the Department of microbiome of Life Sciences Center of National Laboratory

哈萨克斯坦, Astana

参考

  1. Pasrija R., Naime M. The deregulated immune reaction and cytokines release storm (CRS) in COVID-19 disease. Int Immunopharmacol. 2021; 90: 107225. https://doi.org/10.1016/j.intimp.2020.107225. PMID: 33302033. PMCID: PMC7691139.
  2. Mehta P., McAuley D.F., Brown M. et al. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395(10229): 1033–34. https://doi.org/10.1016/s0140-6736(20)30628-0. PMID: 32192578. PMCID: PMC7270045.
  3. Tanveer A., Akhtar B., Sharif A. et al. Pathogenic role of cytokines in COVID-19, its association with contributing co-morbidities and possible therapeutic regimens. Inflammopharmacology. 2022; 30(5): 1503–16. https://doi.org/10.1007/s10787-022-01040-9. PMID: 35948809. PMCID: PMC9365214.
  4. Bekbossynova M., Tauekelova A., Sailybayeva A. et al. Unraveling acute and post-COVID cytokine patterns to anticipate future challenges. J Clin Med. 2023; 12(16): 5224. https://doi.org/10.3390/jcm12165224. PMID: 37629267. PMCID: PMC10455949.
  5. Mussabay K., Kozhakhmetov S., Dusmagambetov M. et al. Gut microbiome and cytokine profiles in post-COVID syndrome. Viruses. 2024; 16(5): 722. https://doi.org/10.3390/v16050722. PMID: 38793604. PMCID: PMC11126011.
  6. Siu K., Yuen K., Castano Rodriguez C. et al. Severe acute respiratory syndrome Coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3 dependent ubiquitination of ASC. FASEB J. 2019; 33(8): 8865–77. https://doi.org/10.1096/fj.201802418r. PMID: 31034780. PMCID: PMC6662968.
  7. DeDiego M.L., Nieto-Torres J.L., Regla-Nava J.A. et al. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 2014; 88(2): 913–24. https://doi.org/10.1128/jvi.02576-13. PMID: 24198408. PMCID: PMC3911641.
  8. Dinarello C.A., van der Meer J.W.M. Treating inflammation by blocking interleukin-1 in humans. Semin Immunol. 2013; 25(6): 469–84. https://doi.org/10.1016/j.smim.2013.10.008. PMID: 24275598. PMCID: PMC3953875.
  9. McKinstry K.K., Alam F., Flores-Malavet V. et al. Memory CD4 T cell-derived IL-2 synergizes with viral infection to exacerbate lung inflammation. PLoS Pathog. 2019; 15(8): e1007989. https://doi.org/10.1371/journal.ppat.1007989. PMID: 31412088. PMCID: PMC6693742.
  10. Zheng Y.-Y., Ma Y.-T., Zhang J.-Y., Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020; 17(5): 259–60. https://doi.org/10.1038/s41569-020-0360-5. PMID: 32139904. PMCID: PMC7095524.
  11. Adamo S., Chevrier S., Cervia C. et al. Profound dysregulation of T cell homeostasis and function in patients with severe COVID-19. Allergy. 2021; 76(9): 2866–81. https://doi.org/10.1111/all.14866. PMID: 33884644. PMCID: PMC8251365.
  12. Bulow Anderberg S., Luther T., Berglund M. et al. Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients. Cytokine. 2021; 138: 155389. https://doi.org/10.1016/j.cyto.2020.155389. PMID: 33348065. PMCID: PMC7833204.
  13. 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. https://doi.org/10.1016/s0140-6736(20)30183-5. PMID: 31986264. PMCID: PMC7159299.
  14. Diao B., Wang C., Tan Y. et al. Reduction and functional exhaustion of t cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol. 2020; 11: 827. https://doi.org/10.3389/fimmu.2020.00827. PMID: 32425950. PMCID: PMC7205903.
  15. Zhao Y., Qin L., Zhang P. et al. Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease. JCI Insight. 2020; 5(13): 139834. https://doi.org/10.1172/jci.insight.139834. PMID: 32501293. PMCID: PMC7406242.
  16. Fields J.K., Günther S., Sundberg E.J. Structural basis of IL-1 family cytokine signaling. Front Immunol. 2019; 10: 1412. https://doi.org/10.3389/fimmu.2019.01412. PMID: 31281320. PMCID: PMC6596353.
  17. Herold T., Jurinovic V., Arnreich C. et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immun. 2020; 146(1): 128–136.e4. https://doi.org/10.1016/j.jaci.2020.05.008. PMID: 32425269. PMCID: PMC7233239.
  18. van de Veerdonk F.L., Netea M.G. Blocking IL-1 to prevent respiratory failure in COVID-19. Crit Care. 2020; 24(1): 445. https://doi.org/10.1186/s13054-020-03166-0. PMID: 32682440. PMCID: PMC7411343.
  19. Jamilloux Y., Henry T., Belot A. et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev. 2020; 19(7): 102567. https://doi.org/10.1016/j.autrev.2020.102567. PMID: 32376392. PMCID: PMC7196557.
  20. Ma A., Zhang L., Ye X. et al. High levels of circulating IL-8 and soluble IL-2R are associated with prolonged illness in patients with severe COVID-19. Front Immunol. 2021; 12: 626235. https://doi.org/10.3389/fimmu.2021.626235. PMID: 33584733. PMCID: PMC7878368.
  21. Chi Y., Ge Y., Wu B. et al. Serum cytokine and chemokine profile in relation to the severity of coronavirus disease 2019 in China. J Infect Dis. 2020; 222(5): 746–54. https://doi.org/10.1093/infdis/jiaa363. PMID: 32563194. PMCID: PMC7337752.
  22. Chang Y., Bai M., You Q. Associations between serum interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10) and disease severity of COVID-19: A systematic review and meta-analysis. Biomed Res Int. 2022; 2022: 2755246. https://doi.org/10.1155/2022/2755246. PMID: 35540724. PMCID: PMC9079324.
  23. Pittman R.N. Regulation of tissue oxygenation. San Rafael (CA): Morgan & Claypool Life Sciences; 2011. URL: https://www.ncbi.nlm.nih.gov/books/NBK54104/ (date of access – 28.08.2024).
  24. Murakami M., Kamimura D., Hirano T. Pleiotropy and specificity: Insights from the interleukin 6 family of cytokines. Immunity. 2019; 50(4): 812–31. https://doi.org/10.1016/j.immuni.2019.03.027. PMID: 30995501.
  25. Hirano T., Murakami M. COVID-19: A new virus, but a familiar receptor and cytokine release syndrome. Immunity. 2020; 52(5): 731–33. https://doi.org/10.1016/j.immuni.2020.04.003. PMID: 32325025. PMCID: PMC7175868.
  26. Blanco-Melo D., Nilsson-Payant B.E., Liu W.C. et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020; 181(5): 1036–45.e9. https://doi.org/10.1016/j.cell.2020.04.026. PMID: 32416070. PMCID: PMC7227586.
  27. Yang L., Xie X., Tu Z. et al. The signal pathways and treatment of cytokine storm in COVID-19. Signal Transduct Target Ther. 2021; 6: 255. https://doi.org/10.1038/s41392-021-00679-0. PMID: 34234112. PMCID: PMC8261820.

补充文件

附件文件
动作
1. JATS XML
下载
2. Fig. 1. Box plot diagram of interleukin expression levels in dynamics from points T0-T5 in the studied patients

下载 (561KB)
索引源数据
3. Figure 2. Correlation analysis between cytokine levels, disease severity, virus strains, and clinical data in the studied COVID-19 patients

下载 (617KB)
索引源数据
4. Fig. 3. Correlation of the heat map: A - correlation between the severity of the disease and the results of laboratory blood analysis; B - correlation between the severity of the disease and cytokine levels

下载 (575KB)
索引源数据
5. Fig. 4. Analysis of the importance of cytokine signs

下载 (668KB)
索引源数据
6. Fig. 5. Pathophysiology of COVID-19 infection

下载 (1MB)
索引源数据

版权所有 © Bionika Media, 2024