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INVITED EDITORIAL
Year : 2020  |  Volume : 18  |  Issue : 3  |  Page : 156-157

Role of plasma exchange in COVID-19


Professor of Intensive Care, The George Institute for Global Health, Sydney, Australia

Date of Submission16-Apr-2020
Date of Decision19-Apr-2020
Date of Acceptance02-May-2020
Date of Web Publication22-May-2020

Correspondence Address:
Prof. Bala Venkatesh
The George Institute for Global Health, Sydney
Australia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmi.cmi_58_20

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How to cite this article:
Venkatesh B. Role of plasma exchange in COVID-19. Curr Med Issues 2020;18:156-7

How to cite this URL:
Venkatesh B. Role of plasma exchange in COVID-19. Curr Med Issues [serial online] 2020 [cited 2020 Aug 8];18:156-7. Available from: http://www.cmijournal.org/text.asp?2020/18/3/156/284738



The COVID-19 pandemic has resulted in >1.6 million infections and an associated crude mortality rate of 5.9%. It has placed an unprecedented demand on healthcare around the world, and in some countries, surges in infection rates have overwhelmed the capacity of health-care services. The ease of transmissibility, the rapidity of global spread, and a high number of deaths in the older population and those with comorbidities have, understandably, generated a lot of concern and anxiety among members of the public, health -care workers, and administrators about the appropriate way to manage the pandemic.

A substantial body of literature has provided detailed insight into mechanisms of disease – including the role of the angiotensin-converting enzyme 2 receptor, cytokine storm, macrophage activation, and a dysregulated immunological response.[1] Capitalizing on this knowledge, several trials are underway to test the efficacy of antiviral agents, antimalarial agents, angiotensin receptor blockers, corticosteroids, and immune modulators.[2]

In this context, a review article by Alexander et al.[3] proposes that plasma exchange (PEX) and low-dose steroids may be potential therapies based on the observation that secondary hemophagocytic lymphohistiocytosis (sHLH) may be responsible for some of the deaths in adult patients with severe COVID-19. They report their experience of low-volume PEX with low-dose steroids in the treatment of adult patients with sHLH and acute liver failure caused by dengue virus and other nonviral triggers.

PEX has been used in clinical practice for a variety of conditions such as autoimmune diseases, Guillain–Barré syndrome and chronic polyneuropathy, and thrombotic thrombocytopenic purpura.[4] The mechanism of action of PEX is based on the removal, for example, of pathogenic antibodies, complement fractions, clotting factors, immune complexes, and cytokines or other macromolecules in the plasma, or less frequently albumin-bound small molecules (drugs or toxins) that remain predominantly intravascular.

Is there biological plausibility that PEX may be of benefit in COVID-19? Multiple reports point to a cytokine storm in COVID-19, predominantly of pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6,[5] which are cleared during PEX.[6] Hyperferritinemia suggestive of macrophage activation has been reported in COVID-19.[7] PEX has been tried with variable success in fulminant macrophage activation syndromes. COVID-19 has been reported to be associated with coagulopathy and elevated antiphospholipid antibodies,[8] a condition amenable to PEX. A recent publication of recovery of patients with severe COVID-19 infection following the transfusion of convalescent plasma suggests the possibility that besides antibodies limiting viral replication, other plasma components may play a part.[9] An in vitro study has demonstrated that lectin affinity plasmapheresis was able to clear lentivirus particles pseudotyped with MERS-CoV S-protein (another coronavirus) from body fluids.[10] The coronavirus particle responsible for COVID-19 infection has a diameter of 60–100 nm-1, which is smaller than the pore size of PEX filters, and therefore, filtration of circulating viruses is possible.

Reports are emerging of the use of blood purification as rescue therapy in COVID-19.[11] A small case series of 3 patients undergoing blood purification therapy for cytokine storm in COVID-19 has been published – one with PEX and the other two patients with oXiris adsorption system. Two of these patients survived.

However, any enthusiasm for the deployment of such therapies must be balanced against the risks. In addition to the recognized adverse effects associated with PEX, given its easy transmissibility, the risk of nosocomial infection needs to be considered. Moreover, transfusion-associated lung injury after PEX has been reported.[12] In septic shock, a condition typically associated with cytokine storm, extracorporeal blood purification techniques have been shown to improve the hemodynamic status, but robust data from clinical trials showing improvements in outcome are lacking.[13] Preliminary reports of improved respiratory function and reduction in immunological mediators in patients following blood purification therapies with ARDS secondary to varied etiologies[14],[15],[16],[17] suggest a potential role for PEX, but large scale studies are required to assess the safety and efficacy.

Based on the currently available evidence, PEX cannot be recommended for the routine management of COVID-19 patients. Trials of convalescent plasma are being planned, but there are no registered trials of PEX in COVID-19 on clinicaltrials.gov.[2] Further understanding of the pathobiology of COVID-19 coupled with clinical reports of rescue PEX will provide the foundations for the planning of future clinical trials of blood purification therapies in this disease.



 
  References Top

1.
1. Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses 2020;12. pii: E372.  Back to cited text no. 1
    
2.
Available from: http://www.clinicaltrials.gov. [Last accessed on 2020 Apr 11].  Back to cited text no. 2
    
3.
Alexander V, Zachariah U, Goel A, Kandasamy S, Chacko B, Punitha JV, et al. Low-volume plasma exchange and low-dose steroid to treat secondary hemophagocytic lymphohistiocytosis: A potential treatment for severe COVID-19? Curr Med Issues 2020;18:77-82.  Back to cited text no. 3
  [Full text]  
4.
Vendramin C, Scully M. Indications of plasma exchanges in combination with intravenous immunoglobulins or therapeutic monoclonal antibodies. How to combine them? Presse Med 2019;48:354-9.  Back to cited text no. 4
    
5.
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunologic features in severe and moderate coronavirus disease 2019. J Clin Invest 2020. pii: 137244.  Back to cited text no. 5
    
6.
Mao WL, Chen Y, Chen YM, Li LJ. Changes of serum cytokine levels in patients with acute on chronic liver failure treated by plasma exchange. J Clin Gastroenterol 2011;45:551-5.  Back to cited text no. 6
    
7.
McGonagle D, Sharif K, O'Regan A, Bridgewood C. Interleukin-6 use in COVID-19 pneumonia related macrophage activation syndrome. Autoimmun Rev 2020:102537.   Back to cited text no. 7
    
8.
Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med 2020;382:e38.  Back to cited text no. 8
    
9.
Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020. [Epub ahead of print]. PMID: 32219428.  Back to cited text no. 9
    
10.
Koch B, Schult-Dietrich P, Büttner S, Dilmaghani B, Lohmann D, Baer PC, et al. Lectin affinity plasmapheresis for middle east respiratory syndrome-coronavirus and Marburg virus glycoprotein elimination. Blood Purif 2018;46:126-33.  Back to cited text no. 10
    
11.
Ma J, Xia P, Zhou Y, Liu Z, Zhou X, Wang J, et al. Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19. Clin Immunol 2020;214:108408.  Back to cited text no. 11
    
12.
Mateen FJ, Gastineau D. Transfusion related acute lung injury (TRALI) after plasma exchange in myasthenic crisis. Neurocrit Care 2008;8:280-2.  Back to cited text no. 12
    
13.
Putzu A, Schorer R, Lopez-Delgado JC, Cassina T, Landoni G. Blood Purification and Mortality in Sepsis and Septic Shock: A Systematic Review and Meta-analysis of Randomized Trials. Anesthesiology 2019;131:580-93.  Back to cited text no. 13
    
14.
Matsuda K, Moriguchi T, Oda S, Hirasawa H. Efficacy of continuous hemodiafiltration with a cytokine-adsorbing hemofilter in the treatment of acute respiratory distress syndrome. Contrib Nephrol 2010;166:83-92.  Back to cited text no. 14
    
15.
Fonseka CL, Lekamwasam S. Role of plasmapheresis and extracorporeal membrane oxygenation in the treatment of leptospirosis complicated with pulmonary hemorrhages. J Trop Med 2018:4520185.  Back to cited text no. 15
    
16.
Geri G, Terrier B, Heshmati F, Moussaoui H, Massot J, Mira JP, et al. Effect of plasma exchange in acute respiratory failure due to Anti-neutrophil cytoplasmic antibody-associated vasculitis. Crit Care 2018;22:328.  Back to cited text no. 16
    
17.
Patel P, Nandwani V, Vanchiere J, Conrad SA, Scott LK. Use of therapeutic plasma exchange as a rescue therapy in 2009 pH1N1 influenza A-an associated respiratory failure and hemodynamic shock. Pediatr Crit Care Med 2011;12:e87-9.  Back to cited text no. 17
    




 

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