Efficacy of convalescent plasma for treatment of COVID-19 in Uganda

Bruce Kirenga, Pauline Byakika-Kibwika, Winters Muttamba, Alex Kayongo, Namakula Olive Loryndah, Levicatus Mugenyi, Noah Kiwanuka, John Lusiba, Angella Atukunda, Raymond Mugume, Francis Ssali, Henry Ddungu, Winceslaus Katagira, Rogers Sekibira, Cissy Kityo, Dorothy Kyeyune, Susan Acana, Hellen Aanyu-Tukamuhebwa, Wilberforce Kabweru, Fred Nakwagala, Bernard Sentalo Bagaya, Ivan Kimuli, Rebecca Nantanda, Esther Buregyeya, Baterana Byarugaba, Charles Olaro, Henry Mwebesa, Moses Lutaakome Joloba, Trishul Siddharthan, William Bazeyo, Bruce Kirenga, Pauline Byakika-Kibwika, Winters Muttamba, Alex Kayongo, Namakula Olive Loryndah, Levicatus Mugenyi, Noah Kiwanuka, John Lusiba, Angella Atukunda, Raymond Mugume, Francis Ssali, Henry Ddungu, Winceslaus Katagira, Rogers Sekibira, Cissy Kityo, Dorothy Kyeyune, Susan Acana, Hellen Aanyu-Tukamuhebwa, Wilberforce Kabweru, Fred Nakwagala, Bernard Sentalo Bagaya, Ivan Kimuli, Rebecca Nantanda, Esther Buregyeya, Baterana Byarugaba, Charles Olaro, Henry Mwebesa, Moses Lutaakome Joloba, Trishul Siddharthan, William Bazeyo

Abstract

Rationale: Convalescent plasma (CCP) has been studied as a potential therapy for COVID-19, but data on its efficacy in Africa are limited.

Objective: In this trial we set out to determine the efficacy of CCP for treatment of COVID-19 in Uganda.

Measurements: Patients with a positive SARS-CoV-2 reverse transcriptase (RT)-PCR test irrespective of disease severity were hospitalised and randomised to receive either COVID-19 CCP plus standard of care (SOC) or SOC alone. The primary outcome was time to viral clearance, defined as having two consecutive RT-PCR-negative tests by day 28. Secondary outcomes included time to symptom resolution, clinical status on the modified WHO Ordinal Clinical Scale (≥1-point increase), progression to severe/critical condition (defined as oxygen saturation <93% or needing oxygen), mortality and safety.

Main results: A total of 136 patients were randomised, 69 to CCP+SOC and 67 to SOC only. The median age was 50 years (IQR: 38.5-62.0), 71.3% were male and the median duration of symptom was 7 days (IQR=4-8). Time to viral clearance was not different between the CCP+SOC and SOC arms (median of 6 days (IQR=4-11) vs 4 (IQR=4-6), p=0.196). There were no statistically significant differences in secondary outcomes in CCP+SOC versus SOC: time to symptom resolution (median=7 (IQR=5-7) vs 7 (IQR=5-10) days, p=0.450), disease progression (9 (22.0%) vs 7 (24.0%) patients, p=0.830) and mortality (10 (14.5%) vs 8 (11.9%) deaths, p=0.476).

Conclusion: In this African trial, CCP therapy did not result in beneficial virological or clinical improvements. Further trials are needed to determine subgroups of patients who may benefit from CCP in Africa.Trial registration number NCT04542941.

Keywords: COVID-19; respiratory infection; viral infection.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Enrolment and randomisation into the trial. CCP, convalescent plasma; SOC, standard of care.
Figure 2
Figure 2
Kaplan-Meier curve showing time to viral clearance by intervention group (p=0.378). CCP, convalescent plasma; SOC, standard of care.
Figure 3
Figure 3
Kaplan-Meier curves showing time to first deterioration (A) and death (B) by intervention group. There were no significant differences: first deterioration (p=0.372) and death (p=0.633). CCP, convalescent plasma; SOC, standard of care.

References

    1. Uganda Ministry of health Covid 19 pandemic. Available: [Accessed 20 Mar 2021].
    1. Liu Y, Morgenstern C, Kelly J, et al. . The impact of non-pharmaceutical interventions on SARS-CoV-2 transmission across 130 countries and territories. BMC Med 2021;19:1–12. 10.1186/s12916-020-01872-8
    1. Callaway E, Ledford H. How to redesign COVID vaccines so they protect against variants. Nature 2021;590:15–16. 10.1038/d41586-021-00241-6
    1. Mahase E. Covid-19: what new variants are emerging and how are they being investigated? BMJ 2021;372:n158. 10.1136/bmj.n158
    1. Government of Uganda . National Guidelines for Management of Covid-19 - Ministry of Health. Available: [Accessed 10 Mar 2021].
    1. Xu X, Han M, Li T, et al. . Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A 2020;117:10970–5. 10.1073/pnas.2005615117
    1. Medicine R-CIJNEJo . Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N Engl J Med 2021. 10.1056/NEJMoa2100433
    1. Horby PW, Pessoa-Amorim G, Peto L. Tocilizumab in patients admitted to hospital with COVID-19 (recovery): preliminary results of a randomised, controlled, open-label, platform trial. Medrxiv 2021. 10.1101/2021.02.11.21249258
    1. NIo H. The COVID-19 treatment guidelines panel’s statement on the emergency use authorization of convalescent plasma for the treatment of COVID-19, 2020.
    1. Medicine RCGJNEJo . Dexamethasone in hospitalized patients with Covid-19—preliminary report, 2020.
    1. Wang Y, Zhang D, Du G, et al. . Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395:1569–78. 10.1016/S0140-6736(20)31022-9
    1. RAMBAR AC. Convalescent serum and pooled plasma in communicable diseases. U S Nav Med Bull 1946;46:93–6.
    1. Garraud O, Heshmati F, Pozzetto B, et al. . Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow. Transfus Clin Biol 2016;23:39–44. 10.1016/j.tracli.2015.12.003
    1. Winkler AM, Koepsell SA, SAJCoih K. The use of convalescent plasma to treat emerging infectious diseases. Curr Opin Hematol 2015;22:521–6. 10.1097/MOH.0000000000000191
    1. Budhiraja S, Dewan A, Aggarwal R, et al. . Effectiveness of convalescent plasma in Indian patients with COVID-19. Blood Cells Mol Dis 2021;88:102548. 10.1016/j.bcmd.2021.102548
    1. Olivares-Gazca JC, Priesca-Marín JM, Ojeda-Laguna M, et al. . Infusion of convalescent plasma is associated with clinical improvement in critically ill patients with COVID-19: a pilot study. RIC 2020;72:159–64. 10.24875/RIC.20000237
    1. Simonovich VA, Burgos Pratx LD, Scibona P, et al. . A randomized trial of convalescent plasma in Covid-19 severe pneumonia. N Engl J Med 2021;384:619–29. 10.1056/NEJMoa2031304
    1. Libster R, Pérez Marc G, Wappner D. Early high-titer plasma therapy to prevent severe Covid-19 in older adults 2021.
    1. Li L, Zhang W, Hu Y, et al. . Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19. JAMA 2020;324:460. 10.1001/jama.2020.10044
    1. Joyner MJ, Senefeld JW, Klassen SA, et al. . Effect of convalescent plasma on mortality among hospitalized patients with COVID-19: initial three-month experience. medRxiv 2020. 10.1101/2020.08.12.20169359. [Epub ahead of print: 12 Aug 2020].
    1. Gharbharan A, Jordans CCE, GeurtsvanKessel C, et al. . Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection. Nat Commun 2021;12:1–12. 10.1038/s41467-021-23469-2
    1. Agarwal A, Mukherjee A, Kumar G, et al. . Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID trial). BMJ 2020;151:m3939. 10.1136/bmj.m3939
    1. Dai W, Gu H, Hao S. Potential benefits, mechanisms, and uncertainties of convalescent plasma therapy for COVID-19. Blood Sci 2020;2:71–5. 10.1097/BS9.0000000000000047
    1. Flyak AI, Ilinykh PA, Murin CD, et al. . Mechanism of human antibody-mediated neutralization of Marburg virus. Cell 2015;160:893–903. 10.1016/j.cell.2015.01.031
    1. Lu C-L, Murakowski DK, Bournazos S, et al. . Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science 2016;352:1001–4. 10.1126/science.aaf1279
    1. Liu Q, Fan C, Li Q, et al. . Antibody-dependent-cellular-cytotoxicity-inducing antibodies significantly affect the post-exposure treatment of Ebola virus infection. Sci Rep 2017;7:1–11. 10.1038/srep45552
    1. Muttamba W, Lusiba J, Namakula LO, et al. . Feasibility of collecting and processing of COVID-19 convalescent plasma for treatment of COVID-19 in Uganda. PLoS One 2021;16:e0252306. 10.1371/journal.pone.0252306
    1. Muttamba W, Lusiba J, Namakula LO. Feasibility of collecting and processing of COVID-19 convalescent plasma for treatment of COVID-19 in Uganda 2020.
    1. SARS-CoV-2 (COVID-19) antibody titer assay kit (Spike protein RBD) - ACROBiosystems. Available: [Accessed 05 Sep 2020].
    1. Borghesi A, Maroldi R, RJLrm M. COVID-19 outbreak in Italy: experimental chest X-ray scoring system for quantifying and monitoring disease progression. Radiol Med 2020;125:509–13. 10.1007/s11547-020-01200-3
    1. Rajendran K, Krishnasamy N, Rangarajan J, et al. . Convalescent plasma transfusion for the treatment of COVID-19: systematic review. J Med Virol 2020;92:1475–83. 10.1002/jmv.25961
    1. Li L, Zhang W, Hu Y, et al. . Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. JAMA 2020;324:460–70. 10.1001/jama.2020.10044
    1. Cheng Y, Wong R, Soo YOY, et al. . Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 2005;24:44–6. 10.1007/s10096-004-1271-9
    1. Abolghasemi H, Eshghi P, Cheraghali AM, et al. . Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: results of a multicenter clinical study. Transfus Apher Sci 2020;59:102875. 10.1016/j.transci.2020.102875
    1. Ko J-H, Joo E-J, Park S-J, et al. . Neutralizing antibody production in asymptomatic and mild COVID-19 patients, in comparison with pneumonic COVID-19 patients. J Clin Med 2020;9:2268. 10.3390/jcm9072268
    1. Gharbharan A, Jordans CC, GeurtsvanKessel C. Convalescent plasma for COVID-19. A randomized clinical trial. Medrxiv 2020. 10.1101/2020.07.01.20139857

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться