Plasma from donors recovered from the new Coronavirus 2019 as therapy for critical patients with COVID-19 (COVID-19 plasma study): a multicentre study protocol

Cesare Perotti, Claudia Del Fante, Fausto Baldanti, Massimo Franchini, Elena Percivalle, Edoardo Vecchio Nepita, Elena Seminari, Annalisa De Silvestri, Raffele Bruno, Catherine Klersy, Cesare Perotti, Claudia Del Fante, Fausto Baldanti, Massimo Franchini, Elena Percivalle, Edoardo Vecchio Nepita, Elena Seminari, Annalisa De Silvestri, Raffele Bruno, Catherine Klersy

Abstract

Since the end of 2019, a new coronavirus strain has been reported in the Chinese province of Wuhan, indicated as 2019-nCoV or SARS-CoV-2. In February 2020, the first case of transmission on Italian soil was reported. On March 09, 2020, at the time of protocol design, the Italian Ministry of Health reported 10,149 people who had contracted the virus; of these, 8514 were positive, of which 5038 were hospitalized with symptoms (59.2%) and 877 in intensive care (10.3%), while the remaining 2599 were in home isolation; 631 were deceased (6.2%) and 1004 healed (9.9%). To date there are no studies in the literature that demonstrate its feasibility and efficacy in the context of the worldwide SARS-CoV-2 epidemic. Based upon the little existing evidence, we planned to assess the efficacy of the infusion of hyperimmune plasma in COVID-19 patients in a one-arm proof-of-concept clinical trial. The primary objective of our study is to evaluate the efficacy of the administration of plasma taken from convalescent donors of COVID-19 to critically ill patients with COVID-19 in terms of their survival. Death from any cause will be considered. The main limit of this study is its one-arm proof-of-concept design with only 43 patients enrolled. However, in the absence of previous evidence, larger and/or randomized trials did not appear to be ethically acceptable. Moreover, the results from this study, if encouraging, will allow us to plan further informed large clinical trials. Trial registration: NCT04321421 March 23, 2020.

Keywords: COVID-19; Hyperimmune plasma; Plasmapheresis.

Conflict of interest statement

The authors declared that they have no conflict of interest.

References

    1. World Health Organization (2020) Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. . Accessed 20 Feb 2020.
    1. Clark DR, Jonathan EM, JKB Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020 doi: 10.1016/S0140-6736(20)30317-2.
    1. Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020 doi: 10.1056/NEJMoa2001191.
    1. Marano G, Vaglio S, Pupella S, et al. Convalescent plasma: new evidence for an old therapeutic tool? Blood Transfus. 2016;14(2):152–157. doi: 10.2450/2015.0131-15.
    1. Lu CL, Murakowski DK, Bournazos S, et al. Enhanced clearance ofHIV-1 infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science. 2016;352(6288):1001–1004. doi: 10.1126/science.aaf1279.
    1. Schoofs T, Klein F, Braunschweig M, et al. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science. 2016;352(6288):997–1001. doi: 10.1126/science.aaf0972.
    1. Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically Ill patients with COVID-19 with convalescent plasma. JAMA. 2020 doi: 10.1001/jama.2020.4783.
    1. Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006;145(8):599–609. doi: 10.7326/0003-4819-145-8-200610170-00139.
    1. Hung IF, To KK, Lee C, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011;52:447–456. doi: 10.1093/cid/ciq106.
    1. 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. doi: 10.1378/chest.12-2907.
    1. Mair-Jenkins J, Saavedra-Campos M, Baillie J, 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. 2014;211:80–90. doi: 10.1093/infdis/jiu396.
    1. Lai S. Treatment of severe acute respiratory syndrome. Eur J Clin Microbiol Infect Dis. 2005;24:583–591. doi: 10.1007/s10096-005-0004-z.
    1. 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;10:676–678. doi: 10.1111/j.1469-0691.2004.00956.x.
    1. 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. doi: 10.1016/s1473-3099(20)30141-9.
    1. Rajam G, Sampson J, Carlone GM, Ades EW. An augmented passive immune therapy to treat fulminant bacterial infections. Recent Pat Antiinfect Drug Discov. 2010;5(2):157–167. doi: 10.2174/157489110791233496.
    1. Keller MA, Stiehm ER. Passive immunity in prevention and treatment of infectious diseases. Clin Microbiol Rev. 2000;13(4):602–614. doi: 10.1128/cmr.13.4.602.
    1. Rojas M, Rodriguez Y, Monsalve DM, et al. Convalescent plasma in Covid-19: possible mechanisms of action. Autoimmun Rev. 2020 doi: 10.1016/j.autrev.2020.102554.
    1. . Accessed 11 May 2020.
    1. . Accessed 11 May 2020.

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