The effect of therapeutic plasma exchange and intravenous immunoglobulin therapy on biomarkers and 28-day mortality in patients with COVID-19 in intensive care unit

Korgün Ökmen 1, Asiye Demirel 1 * , İlkay Ceylan 1
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1 Department of Anesthesiology and Reanimation, University of Health Sciences, Bursa Yüksek Ihtisas Training and Research Hospital, Bursa, Turkey
* Corresponding Author
J CLIN MED KAZ, Volume 20, Issue 2, pp. 46-51.
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Background: The aim of our study was to determine the effectiveness of the co-administration of therapeutic plasma exchange and intravenous immunoglobulin therapy in intensive care patients with COVID-19.
Material and methods: In the propensity-matched study 46 patients were evaluated. The groups were defined as patients who received plasmapheresis + IVIg and standard treatment, and patients who received only standard treatment. The primary outcome of the study was determined as a 28-day mortality rate. Secondary outcome measures; demographic data were biomarkers of inflammation at admission and treatment days.
Results: In the evaluation of 23 patients in 2 groups, no statistically significant difference was found between demographic data, vital and respiratory status, additional diseases and treatments applied (p>0.05) .There was no difference in 28-day mortality rates between the two groups (p:0.688). CRP, IL-6 and Ferritin Lymphocytes values in the TPE+IVIg group were lower when compared to the control group in the values measured after the treatment (p<0.05). All inflammatory markers applied in the Cox regression model were associated with survival and no association was found.
Conclusion: In the results of this study, in which we applied TPE and IVIg treatment in combination, it was determined that this treatment method did not provide an additional benefit to the standard treatment. More clear information can be obtained by testing treatment applications in different doses and regimens and by randomized controlled studies.


Ökmen K, Demirel A, Ceylan İ. The effect of therapeutic plasma exchange and intravenous immunoglobulin therapy on biomarkers and 28-day mortality in patients with COVID-19 in intensive care unit. J CLIN MED KAZ. 2023;20(2):46-51.


  • Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020;91(1):157–160.
  • WHO Middle East respiratory syndrome coronavirus (MERS-CoV) summary and literature update; 11 June 2014.
  • CDC Middle East Respiratory Syndrome (MERS); 25th June, 2014
  • Wujtewicz MA, Dylczyk-Sommer A, Aszkiełowicz A, Zdanowski S, Piwowarczyk S, Owczuk R. COVID-19 - what should anaethesiologists and intensivists know about it? Anaesthesiol Intensive Ther. 2020;52(1):34–41.
  • Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science. 2020;368:473–474.
  • Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. HLH Across Specialty Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034.
  • Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18:1094–1099.
  • 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;395:1054–1062.
  • Bauer PR, Ostermann M, Russell L, Robba C, David S, Ferreyro BL, Cid J, Castro P, Juffermans NP, Montini L, Pirani T, Van De Louw A, Nielsen N, Wendon J, Brignier AC, Schetz M, Kielstein JT, Winters JL, Azoulay E; Nine-I Investigators. Plasma exchange in the intensive care unit: a narrative review. Intensive Care Med. 2022;48(10):1382-1396.
  • Reeves HM, Winters JL. The mechanisms of action of plasma exchange. Br J Haematol. 2014;164(3):342–351.
  • Galeotti C, Kaveri SV, Bayry J. IVIG-mediated effector functions in autoimmune and inflammatory diseases. Int Immunol. 2017;29(11):491–498.
  • Hartung H-P. Advances in the understanding of the mechanism of action of IVIg. J Neurol. 2008;255 Suppl 3:3–6.
  • Keith PD, Wells AH, Hodges J, Fast SH, Adams A, Scott LK. The therapeutic efficacy of adjunct therapeutic plasma exchange for septic shock with multiple organ failure: a single-center experience. Critical Care. 2020;24:518.
  • Mascolo S, Carleo MA, Contieri M, Izzo S, Perna A, De Luca A, Esposito V. SARS-CoV-2 and inflammatory responses: From mechanisms to the potential therapeutic use of intravenous immunoglobulin. J Med Virol. 2021;93(5):2654-2661.
  • Faqihi F, Alharthy A, Abdulaziz S, Balhamar A, Alomari A, AlAseri Z, et al. Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial. Int J Antimicrob Agents. 2021;57(5):106334.
  • Shao Z, Feng Y, Zhong L, Xie Q, Lei M, Liu Z, et al. Clinical efficacy of intravenous immunoglobulin therapy in critical ill patients with COVID-19: a multicenter retrospective cohort study. Clin Transl Immunology.2020;9(10):e1192.
  • Esen F, Özcan PE, Orhun G, Polat Ö, Anaklı İ, Alay G et al. Effects of adjunct treatment with intravenous immunoglobulins on the course of severe COVID-19: results from a retrospective cohort study. Curr Med Res Opin.2021;37(4):543–548.
  • Slatinska J, Honsova E, Burgelova M, Slavcev A, Viklicky O. Plasmapheresis and intravenous immunoglobulin in early antibody-mediated rejection of the renal allograft: a single-center experience. Ther Apher Dial. 2009;13(2):108–112.
  • Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70(1):41–55.
  • Albitar O, Ballouze R, Ooi JP, Sheikh Ghadzi SM. Risk factors for mortality among COVID-19 patients. Diabetes Res Clin Pract. 2020;166:108293.
  • Austin PC. Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations. Biom J. 2009;51(1):171–184.
  • T.C. Sağlık Bakanlığı, Halk Sağlığı Genel Müdürlüğü, 23 Mart 2020 tarihli bilim kurulu COVID-19 (SARS-CoV2 Enfeksiyonu) çalışma rehberi. Erişim Tarihi: 30.03.2020 Erişim Linki: rehberi-23032020.pdf.pdf
  • Khamis F, Al-Zakwani I, Hashmi SA, Al Dowaiki S, Al Bahrani M, Pandak N et al.Therapeutic plasma exchange in adults with severe COVID-19 infection. Int J Infect Dis.2020;99:214–218.
  • Hashemian SM, Shafigh N, Afzal G, Jamaati H, Tabarsi P, Marjani M, et al. Plasmapheresis reduces cytokine and immune cell levels in COVID-19 patients with acute respiratory distress syndrome (ARDS). Pulmonology. 2020;S2531-0437(20)30254-3.
  • Patidar GK, Land KJ, Vrielink H, Patidar GK, Land KJ, Vrielink H, et al. Understanding the role of therapeutic plasma exchange in COVID-19: preliminary guidance and practices. Vox Sang. 2021 Vox Sang. 2021;116(7):798-807.
  • Tabarsi P, Barati S, Jamaati H, Haseli S, Marjani M, Moniri A et al. Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial. Int Immunopharmacol. 2021;90:107205.
  • Bongomin F, Asio LG, Ssebambulidde K, Baluku JB. Adjunctive intravenous immunoglobulins (IVIg) for moderate-severe COVID-19: emerging therapeutic roles. Curr Med Res Opin.2021;37(6):903–905.