Secondary Logo

Journal Logo

Letters to the Editor

Extracorporeal Hemoadsorption: An Option for COVID-19-Associated Cytokine Storm Syndrome

Napp, Lars Christian; Bauersachs, Johann

Author Information
doi: 10.1097/SHK.0000000000001568
  • Free

To the Editor:

The novel coronavirus SARS-CoV-2 is rapidly spreading worldwide, and the disease caused by the virus (COVID-19) immensely challenges intensive care units in affected countries with previously unknown speed. While the true mortality of COVID-19 remains to be defined, morbidity in infected patients is often substantial. Specific antiviral treatment strategies and vaccines are lacking but urgently needed to control the pandemic. Many hospitals are urged to allocate therapies such as ventilation and mechanical support. SARS-CoV-2 initially enters through the respiratory tract and often results in viral pneumonia. Of note, beyond hypoxemic lung failure, acute heart failure and cytokine storm are two major determinants of adverse and often fatal outcome (1, 2).

Cytokine storm has been frequently reported to occur in severe COVID-19. Available data suggest that elevated levels of mediators such as interleukin-6 (IL-6), IL-8, tumor necrosis factor, and others indicate a severe course or fatality of the disease (2, 3). Accordingly, it has been recently suggested to screen COVID-19 patients for cytokine storm and a secondary form of hemophagocytic lymphohistiocytosis (HLH) by measuring inflammatory parameters and calculating the H-score (4, 5). Identified patients may be candidates for anti-inflammatory intervention, to mitigate an excessive host response and thereby reduce organ damage. In this context, antibodies against IL-1, the IL-6 receptor, granulocyte-macrophage colony-stimulating factor, as well as inhibitors of Janus-kinase are currently evaluated for treating hyperinflammation in COVID-19. Substantial experience exists with those agents in other inflammatory conditions such as rheumatoid arthritis (6), but the biological processes of these conditions are much better understood than those of COVID-19. In contrast, many aspects of hyperinflammation in this novel disease are still unknown, and specific inhibition of interleukins or other mediators in COVID-19 may thus be associated with potential risk. Steroids represent a more unspecific pharmacological intervention, but there is reasonable doubt whether those are safe and effective in infection with coronaviruses (7).

This said, we suggest considering extracorporeal hemoadsorption for COVID-19-associated cytokine storm syndrome. The currently most often used adsorber (Cytosorb, Cytosorbents Inc, Monmouth Junction, NJ) removes excess amounts of small hydrophobic molecules from the circulation. It has received CE mark for conditions with elevated inflammatory mediators, for hypermyoglobinemia, and for hyperbilirubinemia. Cytosorb has been successfully used in various conditions with hyperinflammation, HLH (8, 9), virus-associated HLH (10, 11), intoxication, sepsis, and others (12). In several observational studies and a randomized controlled trial in patients with septic shock, CytoSorb reduced excess levels of inflammatory mediators, which was associated with a lower vasopressor demand (13–16). Many mediators that characterize a severe course of COVID-19 are adsorbed by Cytosorb. Importantly, efficacy of adsorption is concentration-dependent, i.e., peak blood levels of adsorbable molecules are preferentially reduced. Cytosorb may be installed in ECMO or dialysis circuits, but can also be used stand-alone as hemoperfusion (12). Besides removal of excess amounts of inflammatory mediators, there is a reasonable chance to adsorb molecular motifs of the virus itself, so-called pathogen-associated molecular patterns (17). As such, hemoadsorption would essentially reduce high levels of several mediators and by this “limit the storm” in cytokine storm syndrome, rather than actively targeting individual pathways during inflammation.

Cytosorb has already been used in COVID-19 patients in China and Europe. The scientific community eagerly awaits publication of data from this experience. However, given the immense dynamics of COVID-19 spread right now, the pre-existing experience with this approach in other conditions, and the devastating mortality of complicated COVID-19, we consider it reasonable to employ hemoadsorption in selected COVID-19 patients with cytokine storm before prospective data are available.


1. Ruan Q, Yang K, Wang W, Jiang L, Song J: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 46 (5):846–848, 2020.
2. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395 (10229):1054–1062.
3. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395 (10223):497–506, 2020.
4. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. Hlh Across Speciality Collaboration UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395 (10229):1033–1034, 2020.
5. Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, Coppo P, Hejblum G. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol 66 (9):2613–2620, 2014.
6. Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality. Int J Antimicrob Agents 2020; 105954[Epub ahead of print].
7. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 395 (10223):473–475, 2020.
8. Ornillo C, Kuntsevich V, Astua A, Peng C, Barash I, Capponi VJ, Chan PP, Winchester JF. Mp216 clinical improvement in hemophagocytic lymphohistiocytosis with daily adsorptive hemoperfusion. Nephrol Dialysis Transplant 31: (suppl_1): i412–i420, 2016.
9. Greil C, Roether F, La Rosee P, Grimbacher B, Duerschmied D, Warnatz K. Rescue of cytokine storm due to HLH by hemoadsorption in a CTLA4-deficient patient. J Clin Immunol 37 (3):273–276, 2017.
10. Frimmel S, Hinz M, Schipper J, Bogdanow S, Mitzner S, Koball S. Cytokine adsorption is a promising tool in the therapy of hemophagocytic lymphohistiocytosis. Int J Artif Organs 42 (11):658–664, 2019.
11. Frimmel S, Schipper J, Henschel J, Yu TT, Mitzner SR, Koball S. First description of single-pass albumin dialysis combined with cytokine adsorption in fulminant liver failure and hemophagocytic syndrome resulting from generalized herpes simplex virus 1 infection. Liver Transpl 20 (12):1523–1524, 2014.
12. Napp LC, Ziegeler S, Kindgen-Milles D. Rationale of hemoadsorption during extracorporeal membrane oxygenation support. Blood Purif 48 (3):203–214, 2019.
13. Friesecke S, Stecher SS, Gross S, Felix SB, Nierhaus A. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study. J Artif Organs 20 (3):252–259, 2017.
14. Kogelmann K, Jarczak D, Scheller M, Druner M. Hemoadsorption by CytoSorb in septic patients: a case series. Crit Care 21 (1):74, 2017.
15. Schädler D, Pausch C, Heise D, Meier-Hellmann A, Brederlau J, Weiler N, Marx G, Putensen C, Spies C, Jörres A, et al. The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients:a randomized controlled trial. PLoS One 12 (10):e0187015, 2017.
16. Hawchar F, Laszlo I, Oveges N, Trasy D, Ondrik Z, Molnar Z. Extracorporeal cytokine adsorption in septic shock: a proof of concept randomized, controlled pilot study. J Crit Care 49:172–178, 2019.
17. Tay MZ, Poh CM, Renia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 2020; [Epub ahead of print].
Copyright © 2020 by the Shock Society