Skip to main content

Plasma exchange in critically ill COVID-19 patients

The spectrum of coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to respiratory failure and death of patients [1]. Severely affected patients may develop a cytokine storm-like clinical syndrome with multi-organ failure and a mortality rate of up to 90% [2]. Recently, it has been suggested that plasma exchange (PE) may positively influence this unfavorable course [3].

Here we report on five COVID-19 patients with a median age of 67 years who were admitted to the medical intensive care unit of Heidelberg University Hospital due to respiratory failure. Patients who had received at least one PE until May 15, 2020, were considered for analysis with clinical follow-up until June 15, 2020. Prophylactic antibiotic (piperacillin/tazobactam), antimycotic (caspofungin), and antiviral/immunomodulatory therapy (hydroxychloroquine or maraviroc) was initiated in all patients upon admission according to center practice. Additional treatments that were administered in some distance to PE are given in Table 1. During the course of the disease, patients developed vasopressor-dependent circulatory shock and/or persistent refractory fever (> 40.5 °C) together with increased interleukin 6 levels compatible with the cytokine storm-like clinical syndrome. In addition, all patients had multi-organ failure with acute respiratory distress syndrome (ARDS, 4 severe, 1 moderate) and acute kidney injury of at least KDIGO stage 2. A single PE with a median of 3.39 L of fresh frozen plasma was initiated in all patients followed by one additional treatment in patients 1, 3, and 5. During the PE, striking reduction of inflammatory markers C-reactive protein (− 47%, P = 0.0078) and interleukin 6 (− 74%, P = 0.0078), as well as significant reduction of ferritin (− 49%, P = 0.0078), LDH (− 41%, P = 0.0078), and D-dimer (− 47%, P = 0.016) were observed (Fig. 1a–e). Due to circulatory shock, four patients received vasopressor treatment at the start of the PE that could be substantially reduced during treatment (− 71%, P = 0.031, Fig. 1h). Biochemical and clinical improvement continued over the following days together with an increase in the oxygenation index in 4 out of 5 patients (Fig. 1i). These improvements were achieved with only 1 to 2 PE, which might be a possible indication of a direct pathophysiological influence of PE on the COVID-19-associated cytokine storm-like clinical syndrome. Three of the 5 most critically ill patients are alive, while a 71-year-old male and a 76-year-old female patient died after the therapy was limited due to persistent severe ARDS.

Table 1 Patient characteristics and treatment
Fig. 1
figure1

Changes of biochemical (af) and clinical (gi) parameters during plasma exchange. af The first value after plasma exchange (PE) is compared to the last value before PE. gh Mean values for the 24 h after compared to the 24 h before PE are given. Wilcoxon matched-pairs signed rank test was used for statistical analysis

It has been suggested that a cytokine storm-like clinical syndrome may be responsible for a significant proportion of COVID-19-associated patient deaths [4]. PE improved inflammation, microcirculatory clot formation, and hypotension, thereby improving clinical outcomes. Further studies to test whether (repeated) PE can alter the course of critically ill COVID-19 patients are clearly indicated.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

References

  1. 1.

    Zhou F, Yu T, Du R, 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):1054–62.

    CAS  Article  Google Scholar 

  2. 2.

    Wang D, Yin Y, Hu C, et al. Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China. Crit Care. 2020;24(1):188.

    Article  Google Scholar 

  3. 3.

    Keith P, Day M, Perkins L, Moyer L, Hewitt K, Wells A. A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care. 2020;24(1):128.

    Article  Google Scholar 

  4. 4.

    Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science. 2020;368(6490):473–4.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

There was no funding for the study.

Author information

Affiliations

Authors

Contributions

CM, MAW, MZ, and UM designed the work, CS, and STH collected and analyzed the data, CM and UM interpreted the data, CM, MAW, MZ, and UM drafted the work or substantively revised it, and all authors read and approved the final manuscript.

Corresponding authors

Correspondence to Christian Morath or Uta Merle.

Ethics declarations

Ethics approval and consent to participate

Biochemical and clinical parameters were collected under the ethics vote S148/2020 of the Ethics Committee of Heidelberg University, and informed consent was retrieved from legal representatives of the patients.

Consent for publication

Informed consent was retrieved from legal representatives of the patients.

Competing interests

The authors declare that they have 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

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

Verify currency and authenticity via CrossMark

Cite this article

Morath, C., Weigand, M.A., Zeier, M. et al. Plasma exchange in critically ill COVID-19 patients. Crit Care 24, 481 (2020). https://doi.org/10.1186/s13054-020-03171-3

Download citation