Clinical Trial

. 2022 Feb 15;12(1):2552.

doi: 10.1038/s41598-022-06221-8.

Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial)

Karin van den Berg^{1

2

3}, Tanya Nadia Glatt⁴, Marion Vermeulen^{5

6}, Francesca Little⁷, Ronel Swanevelder⁴, Claire Barrett⁸, Richard Court^{9

10}, Marise Bremer¹⁰, Cynthia Nyoni⁴, Avril Swarts⁴, Cordelia Mmenu⁶, Thomas Crede¹¹, Gerdien Kritzinger¹², Jonathan Naude¹¹, Patryk Szymanski¹¹, James Cowley¹³, Thandeka Moyo-Gwete^{14

15}, Penny L Moore^{14

15}, John Black¹⁶, Jaimendra Singh¹⁷, Jinal N Bhiman^{18

19}, Prinita Baijnath²⁰, Priyesh Mody²⁰, Jacques Malherbe⁸, Samantha Potgieter²¹, Cloete van Vuuren²², Shaun Maasdorp²³, Robert J Wilkinson^{10

24

25}, Vernon J Louw^#¹², Sean Wasserman^#^{10

26}

Affiliations

¹ Medical Division, Translational Research Department, South African National Blood Service, 1 Constantia Blvd, Roodepoort, 1715, South Africa. Karin.vandenberg@sanbs.org.za.
² Division of Clinical Haematology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa. Karin.vandenberg@sanbs.org.za.
³ Division of Clinical Haematology, Department of Internal Medicine, University of the Free State, Bloemfontein, South Africa. Karin.vandenberg@sanbs.org.za.
⁴ Medical Division, Translational Research Department, South African National Blood Service, 1 Constantia Blvd, Roodepoort, 1715, South Africa.
⁵ Division of Clinical Haematology, Department of Internal Medicine, University of the Free State, Bloemfontein, South Africa.
⁶ Operations Division, Operations Testing Department, South African National Blood Service, Roodepoort, South Africa.
⁷ Department of Statistical Sciences, University of Cape Town, Observatory, South Africa.
⁸ School of Clinical Medicine, University of the Free State, Bloemfontein, South Africa.
⁹ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory, South Africa.
¹⁰ Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa.
¹¹ Mitchells Plain Hospital and the University of Cape Town's Department of Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa.
¹² Division of Clinical Haematology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa.
¹³ Operations Division, Processing Department, South African National Blood Service, Roodepoort, South Africa.
¹⁴ National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
¹⁵ MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁶ Department of Medicine, Walter Sisulu University, Livingstone Hospital, Gqeberha, South Africa.
¹⁷ Capital Haematology Hospital and Bone Marrow Transplant Unit, Durban, South Africa.
¹⁸ Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases, Johannesburg, South Africa.
¹⁹ Department of Virology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²⁰ Life Westville Hospital, Westville, South Africa.
²¹ Division of Infectious Diseases, Department of Internal Medicine, University of the Free State, Bloemfontein, South Africa.
²² 3 Military Hospital and Department of Internal Medicine, University of the Free State, Bloemfontein, South Africa.
²³ Pulmonology and Critical Care, Universitas Academic Hospital and Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.
²⁴ Francis Crick Institute, London, NW1 1AT, UK.
²⁵ Department of Infectious Diseases, Imperial College London, London, W12 0NN, UK.
²⁶ Division of Infectious Diseases and HIV Medicine, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Observatory, South Africa.

^# Contributed equally.

PMID: 35169169
PMCID: PMC8847351
DOI: 10.1038/s41598-022-06221-8

Clinical Trial

Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial)

Karin van den Berg et al. Sci Rep. 2022.

. 2022 Feb 15;12(1):2552.

doi: 10.1038/s41598-022-06221-8.

Authors

Affiliations

¹ Medical Division, Translational Research Department, South African National Blood Service, 1 Constantia Blvd, Roodepoort, 1715, South Africa. Karin.vandenberg@sanbs.org.za.
² Division of Clinical Haematology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa. Karin.vandenberg@sanbs.org.za.
³ Division of Clinical Haematology, Department of Internal Medicine, University of the Free State, Bloemfontein, South Africa. Karin.vandenberg@sanbs.org.za.
⁴ Medical Division, Translational Research Department, South African National Blood Service, 1 Constantia Blvd, Roodepoort, 1715, South Africa.
⁵ Division of Clinical Haematology, Department of Internal Medicine, University of the Free State, Bloemfontein, South Africa.
⁶ Operations Division, Operations Testing Department, South African National Blood Service, Roodepoort, South Africa.
⁷ Department of Statistical Sciences, University of Cape Town, Observatory, South Africa.
⁸ School of Clinical Medicine, University of the Free State, Bloemfontein, South Africa.
⁹ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory, South Africa.
¹⁰ Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa.
¹¹ Mitchells Plain Hospital and the University of Cape Town's Department of Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa.
¹² Division of Clinical Haematology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa.
¹³ Operations Division, Processing Department, South African National Blood Service, Roodepoort, South Africa.
¹⁴ National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
¹⁵ MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁶ Department of Medicine, Walter Sisulu University, Livingstone Hospital, Gqeberha, South Africa.
¹⁷ Capital Haematology Hospital and Bone Marrow Transplant Unit, Durban, South Africa.
¹⁸ Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases, Johannesburg, South Africa.
¹⁹ Department of Virology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²⁰ Life Westville Hospital, Westville, South Africa.
²¹ Division of Infectious Diseases, Department of Internal Medicine, University of the Free State, Bloemfontein, South Africa.
²² 3 Military Hospital and Department of Internal Medicine, University of the Free State, Bloemfontein, South Africa.
²³ Pulmonology and Critical Care, Universitas Academic Hospital and Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.
²⁴ Francis Crick Institute, London, NW1 1AT, UK.
²⁵ Department of Infectious Diseases, Imperial College London, London, W12 0NN, UK.
²⁶ Division of Infectious Diseases and HIV Medicine, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Observatory, South Africa.

^# Contributed equally.

PMID: 35169169
PMCID: PMC8847351
DOI: 10.1038/s41598-022-06221-8

Abstract

There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

**Figure 1**
Consort diagram illustrating numbers of participants with moderate-severe COVID-19 randomized (1:1) to treatment with convalescent plasma or placebo.

**Figure 2**
Proportion of clinical outcomes for 103 participants with moderate-severe COVID-19 randomized to treatment with convalescent plasma versus placebo at day 28 post recruitment.

**Figure 3**
Kaplan–Meier survival analysis of time to death and separately for improvement by ≥ 2 BOSCI points in 103 participants with moderate-severe COVID-19 randomized treatment with convalescent plasma versus placebo. *BOSCI: World Health Organization Blueprint Ordinal Scale for Clinical Improvement.

**Figure 4**
Correlation of neutralizing antibody titer and spike optical density, partitioned by clinical improvement status in patients who received CCP.

See this image and copyright information in PMC

References

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Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial)

Affiliations

Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial)

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous