Skip to main content
Download PDF

Extracorporeal cytokine adsorption as an alternative to pharmacological inhibition of IL-6 in COVID-19

Critical Care volume 24, Article number: 514 (2020) Cite this article

The Original Article was published on 11 June 2020

With great interest we read the article by Convertino et al. discussing potential treatment targets for pharmacological immunomodulation in coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS) [1]. We would like to add to the debate some thoughts about cytokine adsorption, which was mentioned only in passing in this discussion.

Following initial reports describing Interleukin-6 (IL-6) as a predictive factor for a negative outcome, extracorporeal cytokine adsorption was discussed as a possible treatment option for severe COVID-19 cases. Initial experience at our center using the CytoSorb® device (CytoSorbents Europe, Berlin, Germany) in combination with veno-venous extracorporeal membrane oxygenation (V-V ECMO) in severe COVID-19 yielded promising results; cytokine adsorption resulted in a more pronounced decrease of IL-6 after initiation of V-V ECMO as compared to patients treated without cytokine adsorption [2].

The use of the term “cytokine storm” in the context of COVID-19 has been challenged, though. While elevated levels of IL-6 are associated with poor outcome, absolute levels in these cases are rather moderately elevated in comparison to other forms of ARDS with extensive IL-6 increases [3]. Inflammatory dysregulation in severe cases is probably more complex and does not only go along with an upregulation of interleukins or TNF-α but also with an impaired interferon response [4].

A major advantage of extracorporeal cytokine adsorption over the other therapeutic approaches discussed in this debate is that it does not selectively block a specific receptor or signal transduction cascade, but it rather reduces particularly elevated concentrations of various inflammatory mediators such as interleukins, TNF-α, and also interferons; these factors have both pro- and anti-inflammatory functions. Only mildly elevated, physiological, or even decreased concentrations are not relevantly altered; thus, over-suppression of the immune response may be prevented [5]. Furthermore, cytokine adsorption can be better controlled than the other mentioned treatment options—it can be terminated at any time without any specific after-effect. These two aspects may be particularly relevant, e.g., in the case of bacterial superinfection in severe COVID-19 when an adequate immune response is required.

In conclusion, we recommend a cautious approach to intervention or “modulation” in the immune response in COVID-19 patients as long as the pathophysiological background remains to be unveiled. All interventions discussed in this debate should be considered experimental and therefore applied and evaluated within clinical trials.

Availability of data and materials

Not applicable.

References

  1. Convertino I, Tuccori M, Ferraro S, Valdiserra G, Cappello E, Focosi D, Blandizzi C. Exploring pharmacological approaches for managing cytokine storm associated with pneumonia and acute respiratory distress syndrome in COVID-19 patients. Crit Care. 2020;24(1):331.

    Article  Google Scholar 

  2. Rieder M, Wengenmayer T, Staudacher D, Duerschmied D, Supady A. Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation. Crit Care. 2020;24(1):435.

    Article  Google Scholar 

  3. Sinha P, Matthay MA, Calfee CS: Is a “Cytokine Storm” relevant to COVID-19? JAMA Intern Med. 2020. https://doi.org/10.1001/jamainternmed.2020.3313.

  4. Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, Pere H, Charbit B, Bondet V, Chenevier-Gobeaux C, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369(6504):718–24.

  5. Poli EC, Alberio L, Bauer-Doerries A, Marcucci C, Roumy A, Kirsch M, De Stefano E, Liaudet L, Schneider AG. Cytokine clearance with CytoSorb(R) during cardiac surgery: a pilot randomized controlled trial. Crit Care. 2019;23(1):108.

    Article  Google Scholar 

Download references

Acknowledgements

None.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Alexander Supady, Daniel Duerschmied, Christoph Bode, Marina Rieder & Achim Lother

  2. Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany

    Alexander Supady, Daniel Duerschmied, Christoph Bode, Marina Rieder & Achim Lother

  3. Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, Germany

    Alexander Supady

  4. Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Achim Lother

Authors
  1. Alexander Supady
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Duerschmied
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christoph Bode
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marina Rieder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Achim Lother
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A Supady designed the paper and prepared the first draft based on preceding discussions with all co-authors. All authors reviewed the draft and approved the final version of the manuscript.

Corresponding author

Correspondence to Alexander Supady.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

Alexander Supady and D Duerschmied received speakers’ honoraria from CytoSorbents, the manufacturer of the CytoSorb® device. The Department of Cardiology and Angiology I received a research grant from CytoSorbents.

Additional information

Publisher’s Note

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

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Supady, A., Duerschmied, D., Bode, C. et al. Extracorporeal cytokine adsorption as an alternative to pharmacological inhibition of IL-6 in COVID-19. Crit Care 24, 514 (2020). https://doi.org/10.1186/s13054-020-03238-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13054-020-03238-1

Critical Care

ISSN: 1364-8535