Log in

The relationship between Nuclear Factor-Kappa B and Inhibitor-Kappa B parameters with clinical course in COVID-19 patients

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

We aimed to investigate the serum Nuclear Factor Kappa B (NF-κB) p105, NF-κB p65 and Inhibitor Kappa B Alpha (IκBα) levels in patients with mild/moderate Coronavirus Disease 2019 (COVID-19) and their association with the course of the disease.

Materials and methods

Blood was drawn from 35 COVID-19 patients who applied to the Department of Emergency Medicine of Istanbul University-Cerrahpasa at the time of diagnosis and from 35 healthy individuals. The patients were evaluated to have mild/moderate degree of disease according to National Early Warning Score 2 (NEWS2) scoring and computed tomography (CT) findings. The markers were studied in the obtained serum samples, using enzyme-linked immunoassay (ELISA). Receiver Operating Characteristic (ROC) analysis was performed. Statistical significance was evaluated to be p < 0.05.

Results

NF-κB p105 levels were significantly higher in the COVID-19 group compared to the control group. C-reactive protein (CRP), D-dimer, ferritin levels of the patients were significantly higher (p < 0.001) compared to the control group, while the lymphocyte count was found lower (p = 0.001). IκBα and NF-κB p65 levels are similar in both groups. Threshold value for NF-κB p105 was above 0.78 ng/mL, sensitivity was 71.4% and specificity was 97.1% (p < 0.05). NF-κB p105 levels at the time of diagnosis of the patients who required supplemental oxygen (O2), were significantly higher (p < 0.01).

Conclusions

The rise in serum NF-κB p105 levels during the early stages of infection holds diagnostic value. Besides its relation with severity might have a prognostic feature to foresee the requirement for supplemental O2 that occurs during hospitalization.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Data availability

No datasets were generated or analysed during the current study.

References

  1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X et al (2020) Clinical features of patients infected with 2019 Novel Coronavirus in Wuhan, China. Lancet 395:497–506. https://doi.org/10.1016/S0140-6736(20)30183-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hirano T, Murakami M (2020) COVID-19: a new virus, but a familiar receptor and cytokine release syndrome. Immunity 52:731–733. https://doi.org/10.1016/j.immuni.2020.04.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. World Health Organization (2020) COVID-19 timeline. https://www.who.int/news/item/27-04-2020who-timeline---covid-19 Accessed 22 May 2024

  4. Osuchowski MF, Winkler MS, Skirecki T, Cajander S, Shankar-Hari M, Lachmann G, Monneret G, Venet F, Bauer M, Brunkhorst FM et al (2021) The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir Med 9:622–642. https://doi.org/10.1016/S2213-2600(21)00218-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A et al (2020) Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 383:120–128. https://doi.org/10.1056/NEJMoa2015432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. de Wit E, van Doremalen N, Falzarano D, Munster VJ, SARS (2016) Recent insights into emerging coronaviruses. Nat Rev Microbiol 14:523–534. https://doi.org/10.1038/nrmicro.2016.81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Coronavirus Cases and Clinical Presentation (2024) https://emedicine.medscape.com/article/2500114-clinical?form=fpf. Accessed 22 May 2024

  8. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, **ang J, Wang Y, Song B, Gu X et al (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395:1054–1062. https://doi.org/10.1016/S0140-6736(20)30566-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. ** Y-H, Cai L, Cheng Z-S, Cheng H, Deng T, Fan Y-P, Fang C, Huang D, Huang L-Q, Huang Q et al (2020) A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-NCoV) infected pneumonia (Standard Version). Mil Med Res 7(4). https://doi.org/10.1186/s40779-020-0233-6

  10. World Health Organization (2020) Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: interim guidance, 13 March 2020. World Health Organization. https://iris.who.int/handle/10665/331446. Accessed 22 May 2024

  11. National Institutes of Health-Clinical Spectrum of SARS-CoV-2 Infection (2024) https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/. Accessed 22 May 2024

  12. Baker KF, Hanrath AT, van der Loeff IS, Kay LJ, Back J, Duncan CJA (2021) National early warning score 2 (NEWS2) to identify inpatient COVID-19 deterioration: a retrospective analysis. Clin Med J R Coll Physicians Lond 21:84–89. https://doi.org/10.7861/CLINMED.2020-0688

    Article  Google Scholar 

  13. Liao Q-J, Ye L-B, Timani KA, Zeng Y-C, She Y-L, Ye L, Wu Z-H (2005) Activation of NF-KappaB by the full-length nucleocapsid protein of the SARS Coronavirus. Acta Biochim Biophys Sin (Shanghai) 37:607–612. https://doi.org/10.1111/j.1745-7270.2005.00082.x

    Article  CAS  PubMed  Google Scholar 

  14. Ghosh S, Hayden MS (2008) New regulators of NF-ΚB in inflammation. Nat Rev Immunol 8:837–848. https://doi.org/10.1038/nri2423

    Article  CAS  PubMed  Google Scholar 

  15. Hayden MS, Ghosh S (2012) NF-ΚB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev 26:203–234. https://doi.org/10.1101/gad.183434.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hinz M, Scheidereit C (2014) The IκB kinase complex in < scp > NF -κB regulation and beyond. EMBO Rep 15:46–61. https://doi.org/10.1002/embr.201337983

    Article  CAS  PubMed  Google Scholar 

  17. Liu T, Zhang L, Joo D, Sun S-C (2017) NF-ΚB signaling in inflammation. Signal Transduct Target Ther 2:17023. https://doi.org/10.1038/sigtrans.2017.23

    Article  PubMed  PubMed Central  Google Scholar 

  18. Elkhodary MSM (2020) Treatment of COVID-19 by controlling the activity of the nuclear factor-Kappa B. CellBio 09:109–121. https://doi.org/10.4236/cellbio.2020.92006

    Article  CAS  Google Scholar 

  19. Farahani M, Niknam Z, Mohammadi Amirabad L, Amiri-Dashatan N, Koushki M, Nemati M, Danesh Pouya F, Rezaei-Tavirani M, Rasmi Y, Tayebi L (2022) Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets. Biomed Pharmacother 145. https://doi.org/10.1016/j.biopha.2021.112420

  20. Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, Hirano T (2020) How COVID-19 induces cytokine storm with high mortality. Inflamm Regen 40:37. https://doi.org/10.1186/s41232-020-00146-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yang Y, Shen C, Li J, Yuan J, Yang M, Wang F, Li G, Li Y, **ng L, Peng L et al (2020) Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome. medRxiv 2, 2020.03.02.20029975

  22. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ (2020) COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395:1033–1034. https://doi.org/10.1016/S0140-6736(20)30628-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kircheis R, Haasbach E, Lueftenegger D, Heyken WT, Ocker M, Planz O (2020) NF-ΚB pathway as a potential target for treatment of critical stage COVID-19 patients. Front Immunol 11:1–11. https://doi.org/10.3389/fimmu.2020.598444

    Article  CAS  Google Scholar 

  24. Barnabei L, Laplantine E, Mbongo W, Rieux-Laucat F, Weil R (2021) NF-ΚB: at the borders of autoimmunity and inflammation. Front Immunol 12:1–27. https://doi.org/10.3389/fimmu.2021.716469

    Article  CAS  Google Scholar 

  25. Robles JP, Zamora M, Adan-Castro E, Siqueiros-Marquez L, de la Martinez G, Clapp C (2022) The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin Α5β1 and NF-ΚB signaling. J Biol Chem 298. https://doi.org/10.1016/j.jbc.2022.101695

  26. Sohn KM, Lee SG, Kim HJ, Cheon S, Jeong H, Lee J, Kim IS, Silwal P, Kim YJ, Paik S et al (2020) COVID-19 patients upregulate toll-like receptor 4-mediated inflammatory signaling that mimics bacterial sepsis. J Korean Med Sci 35:e343. https://doi.org/10.3346/jkms.2020.35.e343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kalemci S, Zeybek A, Kargi AB (2022) Can the development of lung fibrosis be prevented after COVID-19 infection? Kardiochirurgia i Torakochirurgia Pol 19:113. https://doi.org/10.5114/kitp.2022.117505

    Article  Google Scholar 

  28. Fangradt M, Hahne M, Gaber T, Strehl C, Rauch R, Hoff P, Löhning M, Burmester G-R, Buttgereit F (2012) Human monocytes and macrophages differ in their mechanisms of adaptation to hypoxia. Arthritis Res Ther 14. https://doi.org/10.1186/ar4011

  29. Kadhim AS, Abdullah YJ Serum Levels of Interleukin-6, Ferritin, Protein C-R, Dehydrogenase L (2021) D-Dimer, and count of lymphocytes and neutrophils in COVID-19 patients: its correlation to the disease severity. Biomed Biotechnol Res J 5:69–73. https://doi.org/10.4103/bbrj.bbrj_188_20

  30. Balcı S, Poyraz Z, Gülüm C, Aslan G, Tamer L, Çimen MB (2021) Erken Evre COVİD-19 Hastalarında Biyokimyasal Parametrelerin Değerlendirilmesi. Mersin Üniversitesi Sağlık Bilim Derg 14:378–384. https://doi.org/10.26559/mersinsbd.959335

    Article  Google Scholar 

  31. Tufa A, Gebremariam TH, Manyazewal T, Getinet T, Webb D-L, Hellström PM, Genet S (2022) Inflammatory mediators profile in patients hospitalized with COVID-19: a comparative study. Front Immunol 13:1–14. https://doi.org/10.3389/fimmu.2022.964179

    Article  CAS  Google Scholar 

  32. Zhou Q, Zhang L, Dong Y et al (2024) The role of SARS-CoV-2-mediated NF-κB activation in COVID-19 patients. Hypertens Res 47:375–384. https://doi.org/10.1038/s41440-023-01460-2

    Article  PubMed  Google Scholar 

  33. Lai KY, Au SY, Sin KC, Yung SK, Leung AKH (2024) High-dose N-acetylcysteine in an immunocompromised patient with COVID-19: a case report. Hong Kong Med J 30(1):69–71. https://doi.org/10.12809/hkmj2210461Epub 2024 Feb 8. PMID: 38327160

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was funded by Istanbul University Cerrahpasa Faculty of Medicine Scientific Research Projects Section. Project id is 35680.

Author information

Authors and Affiliations

Authors

Contributions

M.K. And M.K. did the source research and wrote the main manuscript. S.B. and M.C. took part in organizing participants. S.B. also reviewed the article. N.C. and S.K. helped with the method. D.K. took part in.

Corresponding author

Correspondence to Melek Karasu.

Ethics declarations

Compliance with ethical standards

This study was performed in line with the principles of the Declaration of Helsinki. This study was carried out with the approval of Istanbul University Cerrahpasa Faculty of Medicine Clinical Research Ethics Committee (08.02.2021; letter E-83045809-604.01.02-25739).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karasu, M., Cevik, M., Biberoglu, S. et al. The relationship between Nuclear Factor-Kappa B and Inhibitor-Kappa B parameters with clinical course in COVID-19 patients. Mol Biol Rep 51, 813 (2024). https://doi.org/10.1007/s11033-024-09729-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11033-024-09729-6

Keywords

Navigation