Convalescent Plasma vs Human Immunoglobulin to Treat COVID-19 Pneumonia

Summary

Background: On December 2019, a new human coronavirus infection (COVID-19) was detected in China. Its infectivity and virulence characteristics caused a rapid spread, being declared pandemic on March 2020. The mortality attributed to the infection ranges between 3 and 10%. Main risk factors are age, male sex, and chronic degenerative comorbidities. Due to the absence of therapeutic options, potential alternatives such as human immunoglobulin or plasma from convalescent patients have been administered. Due to the severity of the disease and the associated mortality, it is urgent to find therapeutic alternatives. Objective: To assess the safety and efficacy of the administration of Convalescent plasma vs human immunoglobulin in critically ill patients with COVID-19 infection. Material and methods: Randomized Controlled trial of patients diagnosed with respiratory infection by COVID-19, with severe respiratory failure without indication of mechanical ventilation, or those who due to their severity are intubated upon admission. Randomization will be performed 2:1 to receive plasma from convalescent patients or human immunoglobulin. Outcomes: The primary outcome will be time to discharge from hospital for improvement. The safety outcomes will be: Kirby index (PaO2/FiO2) evolution and dead.

Timeline

Start

2020-05-06

Primary completion

2020-11-26

Completion

2020-11-26

Publications

• Background Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
• Background Lv DF, Ying QM, Weng YS, Shen CB, Chu JG, Kong JP, Sun DH, Gao X, Weng XB, Chen XQ. Dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a Coronavirus Disease 2019 patient. Clin Chim Acta. 2020 Jul;506:172-175. doi: 10.1016/j.cca.2020.03.032. Epub 2020 Mar 27.
• Background Munster VJ, Koopmans M, van Doremalen N, van Riel D, de Wit E. A Novel Coronavirus Emerging in China - Key Questions for Impact Assessment. N Engl J Med. 2020 Feb 20;382(8):692-694. doi: 10.1056/NEJMp2000929. Epub 2020 Jan 24. No abstract available.
• Background Correction to Lancet Infect Dis 2020; published online March 11, https://doi.org/10.1016/ S1473-3099(20)30144-4. Lancet Infect Dis. 2020 May;20(5):e79. doi: 10.1016/S1473-3099(20)30251-6. Epub 2020 Mar 25. No abstract available.
• Background Cao W, Liu X, Bai T, Fan H, Hong K, Song H, Han Y, Lin L, Ruan L, Li T. High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019. Open Forum Infect Dis. 2020 Mar 21;7(3):ofaa102. doi: 10.1093/ofid/ofaa102. eCollection 2020 Mar.
• Background Xie Y, Cao S, Dong H, Li Q, Chen E, Zhang W, Yang L, Fu S, Wang R. Effect of regular intravenous immunoglobulin therapy on prognosis of severe pneumonia in patients with COVID-19. J Infect. 2020 Aug;81(2):318-356. doi: 10.1016/j.jinf.2020.03.044. Epub 2020 Apr 10. No abstract available.
• Background Wang JT, Sheng WH, Fang CT, Chen YC, Wang JL, Yu CJ, Chang SC, Yang PC. Clinical manifestations, laboratory findings, and treatment outcomes of SARS patients. Emerg Infect Dis. 2004 May;10(5):818-24. doi: 10.3201/eid1005.030640.
• Background Bloch EM, Shoham S, Casadevall A, Sachais BS, Shaz B, Winters JL, van Buskirk C, Grossman BJ, Joyner M, Henderson JP, Pekosz A, Lau B, Wesolowski A, Katz L, Shan H, Auwaerter PG, Thomas D, Sullivan DJ, Paneth N, Gehrie E, Spitalnik S, Hod EA, Pollack L, Nicholson WT, Pirofski LA, Bailey JA, Tobian AA. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest. 2020 Jun 1;130(6):2757-2765. doi: 10.1172/JCI138745.
• Background Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, Liao P, Qiu JF, Lin Y, Cai XF, Wang DQ, Hu Y, Ren JH, Tang N, Xu YY, Yu LH, Mo Z, Gong F, Zhang XL, Tian WG, Hu L, Zhang XX, Xiang JL, Du HX, Liu HW, Lang CH, Luo XH, Wu SB, Cui XP, Zhou Z, Zhu MM, Wang J, Xue CJ, Li XF, Wang L, Li ZJ, Wang K, Niu CC, Yang QJ, Tang XJ, Zhang Y, Liu XM, Li JJ, Zhang DC, Zhang F, Liu P, Yuan J, Li Q, Hu JL, Chen J, Huang AL. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020 Jun;26(6):845-848. doi: 10.1038/s41591-020-0897-1. Epub 2020 Apr 29.
• Background Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.
• Background Zeng QL, Yu ZJ, Gou JJ, Li GM, Ma SH, Zhang GF, Xu JH, Lin WB, Cui GL, Zhang MM, Li C, Wang ZS, Zhang ZH, Liu ZS. Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients With Coronavirus Disease 2019. J Infect Dis. 2020 Jun 16;222(1):38-43. doi: 10.1093/infdis/jiaa228.
• Background Chun S, Chung CR, Ha YE, Han TH, Ki CS, Kang ES, Park JK, Peck KR, Cho D. Possible Transfusion-Related Acute Lung Injury Following Convalescent Plasma Transfusion in a Patient With Middle East Respiratory Syndrome. Ann Lab Med. 2016 Jul;36(4):393-5. doi: 10.3343/alm.2016.36.4.393. No abstract available.
• Background Burnouf T, Radosevich M. Treatment of severe acute respiratory syndrome with convalescent plasma. Hong Kong Med J. 2003 Aug;9(4):309; author reply 310. No abstract available.
• Background Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.
• Background Kong L. Severe acute respiratory syndrome (SARS). Transfus Apher Sci. 2003 Aug;29(1):101. doi: 10.1016/s1473-0502(03)00109-5. No abstract available.
• Background Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. 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 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16.
• Background Soo YO, Cheng Y, Wong R, Hui DS, Lee CK, Tsang KK, Ng MH, Chan P, Cheng G, Sung JJ. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect. 2004 Jul;10(7):676-8. doi: 10.1111/j.1469-0691.2004.00956.x.
• Background Yeh KM, Chiueh TS, Siu LK, Lin JC, Chan PK, Peng MY, Wan HL, Chen JH, Hu BS, Perng CL, Lu JJ, Chang FY. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother. 2005 Nov;56(5):919-22. doi: 10.1093/jac/dki346. Epub 2005 Sep 23.
• Background Beigel JH, Tebas P, Elie-Turenne MC, Bajwa E, Bell TE, Cairns CB, Shoham S, Deville JG, Feucht E, Feinberg J, Luke T, Raviprakash K, Danko J, O'Neil D, Metcalf JA, King K, Burgess TH, Aga E, Lane HC, Hughes MD, Davey RT; IRC002 Study Team. Immune plasma for the treatment of severe influenza: an open-label, multicentre, phase 2 randomised study. Lancet Respir Med. 2017 Jun;5(6):500-511. doi: 10.1016/S2213-2600(17)30174-1. Epub 2017 May 15.
• Background Narick C, Triulzi DJ, Yazer MH. Transfusion-associated circulatory overload after plasma transfusion. Transfusion. 2012 Jan;52(1):160-5. doi: 10.1111/j.1537-2995.2011.03247.x. Epub 2011 Jul 18.
• Background Sheridan C. Convalescent serum lines up as first-choice treatment for coronavirus. Nat Biotechnol. 2020 Jun;38(6):655-658. doi: 10.1038/d41587-020-00011-1. No abstract available.
• Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 May 10;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub6.
• Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 Feb 1;2(2):CD013600. doi: 10.1002/14651858.CD013600.pub5.
• Piechotta V, Iannizzi C, Chai KL, Valk SJ, Kimber C, Dorando E, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 20;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub4.

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