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SAMJ: South African Medical Journal
versão On-line ISSN 2078-5135
versão impressa ISSN 0256-9574
SAMJ, S. Afr. med. j. vol.110 no.7 Pretoria Jul. 2020
http://dx.doi.org/10.7196/SAMJ.2020.v110i7.14983
CORRESPONDENCE
COVID-19: Convalescent plasma as a potential therapy
To the Editor: SARS-CoV-2, the cause of COVID-19, has posed a significant threat to global health. No specific treatment or effective prophylaxis has been established, and care of severely ill patients is largely supportive, with poor outcomes in those requiring ICU admission. Experimental therapies include antiviral agents such as remdesivir,[1] lopinavir/ritonavir[2] and favipiravir,[3-hydroxychloroquine/chloroquine,[4] interleukin-6 inhibitors such as tocilizumab,[5] siltuximab[6] and sarilumab,[7] and COVID-19 convalescent plasma (CCP).[8]
CCP has been included in the treatment guidelines for severe COVID-19 in China,[9] and the Food and Drug Administration has recently approved its use for critically ill COVID-19 patients in the context of clinical trials and through the expanded access programme in the USA.[10] Interest has been expressed in the use of CCP for COVID-19 treatment in South Africa (SA).
CCP refers to plasma collected from donors who have recovered from COVID-19 and are likely to have produced neutralising antibodies to SARS-CoV-2. It is hypothesised that the infusion of plasma with virus-specific antibodies confers immediate transfer of passive immunity to the recipient and may improve the clinical course and outcomes by accelerating viral clearance and antibody-dependent cell-mediated cytotoxicity of infected cells.[11]
The use of convalescent plasma (CP) as passive immunisation to treat viral infections is not novel.[12] Early administration of CP has proved successful in reducing mortality from severe influenza[13,14] as well as the related epidemic coronavirus severe acute respiratory syndrome (SARS)-CoV,[15] and has been used successfully in Middle East respiratory syndrome (MERS)-CoV[16] and Ebola virus disease.[17] Studies using CP in various viral infections have shown improvement of both laboratory and clinical parameters,[13,18-22] including a reduction in the hyperinflammatory cytokine response, which appears to be a critical driver of morbidity and mortality in COVID-19.[23,24] Where CP was used to treat SARS-CoV infections, the absolute risk reduction in mortality ranged between 7% and 23%,[25-30] and CP was associated with earlier discharge from hospital.[15,26,27,30] It is because of the positive results of these trials, in addition to the lack of successful treatment options available at present, that the use of CCP has been considered in the current SARS-CoV-2 pandemic.
Studies of the use of CCP from China have shown potential benefit, including improved survival,[31,32] reductions in viral load[31-33] and improved radiological features.[31,32,34] These studies have various limitiations, including small numbers of patients, lack of blinded, randomised or placebo-controlled trials, and patients receiving a multitude of different therapies. One study involving 6 critically ill patients[33] found that although all the patients became SARS-CoV-2 RNA-negative within 3 days of CCP infusion, 5 eventually died. Consequently, before CCP can be considered as an effective treatment option, testing of its safety and efficacy in large randomised controlled trials has been recommended,[8,35] and trials are underway in the USA, the UK, Canada, Brazil and Italy, as well as several other European countries. Early safety[36] and treatment[37] outcomes appear encouraging, with non-ventilated patients benefiting more than those requiring ventilation. Historical use of CP has shown that it is most effective when used as prophylaxis or early in treatment, and these findings need to be established for CCP.
There are unique challenges around the collection of CP during a pandemic. These include biological, such as ensuring that donors are clinically and virally free of SARS-CoV-2 and with a sufficient antibody titre to be therapeutically effective; logistical, such as travel/movement bans; legal, such as donor consent and eligibility, and regulatory requirements for administration of CP in a clinical trial; and scientific, such as limited commercial availability of validated assays for antibody titre testing. National blood services are uniquely positioned to address and manage these challenges, as they are likely to already have appropriate infrastructure and networks to support the rapid collection, testing and storage of blood products such as CP. While studies have shown that CP is safe, the theoretical risks of receiving any blood products need to be considered, including transfusion-transmissible infections and transfusion-related acute lung injury (TRALI), specifically in the setting of a respiratory virus. These risks need to be mitigated by ensuring that CCP donors comply with all standard eligibility and testing criteria established for regular blood donations; excluding parous female donors to reduce the incidence of TRALI; and using pathogen reduction to target transfusion-transmissible infections. Furthermore, there is a theoretical risk that other non-anti-SARS-CoV-2-neutralising antibodies may cause antibody-dependent enhancement of infection. Internationally, the willingness of recovered patients to donate CCP has ensured a sustainable CCP supply.
With no proven effective therapy against COVID-19 available in SA, and in the context of limited resources to provide care to patients with critical illness, it is a research priority to evaluate potential therapeutic interventions in an SA population. An effective vaccine is required for sustained population immunity, but development, manufacture and scale-up are likely to be several months away. It is therefore appealing to consider CCP, which may offer immediate passive immunity, and production of which could be rapidly scaled to be widely available throughout the country in a matter of weeks. However, we would caution that given the current paucity of data and potential risks and complexities, before the use of CCP can be recommended, randomised controlled trials are needed to establish therapeutic efficacy and safe use for COVID-19 disease.
Conflicts of interest. VJL is non-executive director of the Board of the Western Cape Blood Service.
Karin van den Berg
Translational Research, Medical Division, South African National Blood Service, Roodepoort, South Africa; and Division of Clinical Haematology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa karin.vandenberg@sanbs.org.za
Marion Vermeulen
Operations Testing, Operations Division, South African National Blood Service, Roodepoort, South Africa
Tanya Nadia Glatt
Director, Cellular Therapy Laboratory, South African National Blood Service, Roodepoort, South Africa
Sean Wasserman
Division of Infectious Diseases and HIV Medicine, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa; and Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa
Claire L Barrett
School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
Jonny Peter
Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa; and Allergy and Immunology Unit, University of Cape Town Lung Institute, South Africa
David Brittain
Alberts Cellular Therapy, Netcare Pretoria East Hospital, South Africa
Vernon J Louw
Division of Clinical Haematology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa
References
1. Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med 2020 (epub 10 April 2020). https://doi.org/10.1056/NEJMoa2007016 [ Links ]
2. Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020;382(21):e68. https://doi.org/10.1056/NEJMc2008043 volume and issue: 382:e68 [ Links ]
3. Cai Q, Yang M, Liu D, et al. Experimental treatment with favipiravir for COVID-19: An open-label control study. Engineering (Beijing) 2020 (epub 18 March 2020). https://doi.org/10.1016/j.eng.2020.03.007 [ Links ]
4. Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents 2020;55(4):105932. https://doi.org/10.1016/j.ijantimicag.2020.105932 [ Links ]
5. Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc NatlAcad Sci U S A 2020;117(20):10970-10975. https://doi.org/10.1073/pnas.2005615117 [ Links ]
6. ClinicalTrials.gov. An observational study of the use of siltuximab (SYLVANT) in patients diagnosed with COVID-19 infection who have developed serious respiratory complications (SISCO). ClinicalTrials.gov Identifier: NCT04322188. 26 March 2020. https://clinicaltrials.gov/ct2/show/NCT04322188 (accessed 10 May 2020). [ Links ]
7. ClinicalTrials.gov. Sarilumab COVID-19. ClinicalTrials.gov Identifier: NCT04327388. 31 March 2020. https://clinicaltrials.gov/ct2/show/NCT04327388 (accessed 10 May 2020). [ Links ]
8. Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis 2020;20(4):398-400. https://doi.org/10.1016/S1473-3099(20)30141-9 [ Links ]
9. Treatment guide of COVID-19 pneumonia caused by new coronavirus infection. 7th ed. 3 March 2020. Translated to English. http://www.gov.cn/zhengce/zhengceku/2020-03/04/content_5486705.htm (accessed 10 May 2020). [ Links ]
10. Tanne JH. Covid-19: FDA approves use of convalescent plasma to treat critically ill patients. BMJ 2020;368:m1256. https://doi.org/10.1136/bmj.m1256 [ Links ]
11. Rojas M, Rodriguez Y, Monsalve DM, et al. Convalescent plasma in Covid-19: Possible mechanisms of action. Autoimmun Rev 2020;19(7):102554. https://doi.org/10.1016/j.autrev.2020.102554 [ Links ]
12. Marano G, Vaglio S, Pupella S, et al. Convalescent plasma: New evidence for an old therapeutic tool? Blood Transfus 2016;14(2):152-157. https://doi.org/10.2450/2015.0131-15 [ Links ]
13. Hung IF, To KK, Lee CK, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis 2011;52(4):447-456. https://doi.org/10.1093/cid/ciq106 [ Links ]
14. Hung IFN, To KKW, Lee CK, et al. Hyperimmune IV immunoglobulin treatment: A multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest 2013;144(2):464-473. https://doi.org/10.1378/chest.12-2907 [ Links ]
15. Cheng Y, Wong R, Soo YO, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 2005;24(1):44-46. https://doi.org/10.1007/s10096-004-1271-9 [ Links ]
16. Ko JH, Seok H, Cho SY, et al. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: A single centre experience. Antivir Ther 2018;23(7):617-622. https://doi.org/10.3851/IMP3243 [ Links ]
17. Van Griensven J, Edwards T, de Lamballerie X, et al. Evaluation of convalescent plasma for Ebola virus disease in Guinea. N Engl J Med 2016;374(1):33-42. https://doi.org/10.1056/NEJMoa1511812 [ Links ]
18. Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest 2020;130(4):1545-1548. https://doi.org/10.1172/JCI138003 [ Links ]
19. Casadevall A, Scharff MD. Return to the past: The case for antibody-based therapies in infectious diseases. Clin Infect Dis 1995;21(1):150-161. https://doi.org/10.1093/clinids/21.1.150 [ Links ]
20. Casadevall A, Dadachova E, Pirofski LA. Passive antibody therapy for infectious diseases. Nat Rev Microbiol 2004;2(9):695-703. https://doi.org/10.1038/nrmicro974 [ Links ]
21. Sahr F, Ansumana R, Massaquoi TA, et al Evaluation of convalescent whole blood for treating Ebola virus disease in Freetown, Sierra Leone. J Infect 2017;74(3):302-309. https://doi.org/10.1016/j.jinf.2016.11.009 [ Links ]
22. Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med 2007;357(14):1450-1451. https://doi.org/10.1056/NEJMc070359 [ Links ]
23. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020 (epub 13 March 2020). https://doi.org/10.1001/jamainternmed.2020.0994 [ Links ]
24. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497-506. https://doi.org/10.1016/S0140-6736(20)30183-5 [ Links ]
25. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: A systematic review and exploratory meta-analysis. J Infect Dis 2015;211(1):80-90. https://doi.org/10.1093/infdis/jiu396 [ Links ]
26. Soo YO, Cheng Y, Wong R, et al. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect 2004;10(7):676-678. https://doi.org/10.1111/j.1469-0691.2004.00956.x [ Links ]
27. Zhou XZ, Zhao M, Wang FS, et al. [Epidemiologic features, clinical diagnosis and therapy of first cluster of patients with severe acute respiratory syndrome in Beijing area]. Zhonghua Yi Xue Za Zhi 2003;83(12):1018-1022. [ Links ]
28. Nie QH, Luo XD, Hui WL. Advances in clinical diagnosis and treatment of severe acute respiratory syndrome. World J Gastroenterol 2003;9(6):1139-1143. https://doi.org/10.3748/wjg.v9.i6.1139 [ Links ]
29. Wong VW, Dai D, Wu AK, Sung JJ. Treatment of severe acute respiratory syndrome with convalescent plasma. Hong Kong Med J 2003;9(3):199-201. [ Links ]
30. Yeh KM, Chiueh TS, Siu LK, et al. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother 2005;56(5):919-922. https://doi.org/10.1093/jac/dki346 [ Links ]
31. Duan K, Liu B, Li C, et al Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A 2020;117(17):9490-9496. https://doi.org/10.1073/pnas.2004168117 [ Links ]
32. Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020;323(16):1582-1589. https://doi.org/10.1001/jama.2020.4783 [ Links ]
33. Zeng QL, Yu ZJ, Gou JJ, et al. Effect of convalescent plasma therapy on viral shedding and survival in COVID-19 patients. J Infect Dis 2020;jiaa228. https://doi.org/10.1093/infdis/jiaa228 [ Links ]
34. Xinhua. China puts 245 COVID-19 patients on convalescent plasma therapy. http://www.xinhuanet.com/english/2020-02/28/c_138828177.htm (accessed 23 April 2020). [ Links ]
35. Bloch EM, Shoham S, Casadevall A, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest 2020;130(6):2757-2765. https://doi.org/10.1172/JCI138745 [ Links ]
36. Joyner M, Scott Wright R, Fairweather D, et al. Early safety indicators of COVID-19 convalescent plasma in 5,000 patients. Medrxiv, 14 May 2020. https://doi.org/10.1101/2020.05.12.20099879 (accessed 3 June 2020). [ Links ]
37. Liu STH, Lin H-M, Baine I, et al. Convalescent plasma treatment of severe COVID-19: A matched control study. Medrxiv, 22 May 2020. https://doi.org/10.1101/2020.05.20.20102236 (accessed 3 June 2020). [ Links ]