Hamostaseologie 2023; 43(01): 067-074
DOI: 10.1055/a-1987-3682
Review Article

Immune Plasma for the Treatment of COVID-19: Lessons Learned so far

Hubert Schrezenmeier
1   Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany
2   Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
,
Simone Hoffmann
1   Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany
2   Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
,
Henrike Hofmann
1   Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany
2   Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
,
Thomas Appl
1   Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany
2   Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
,
Bernd Jahrsdörfer
1   Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany
2   Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
,
Erhard Seifried
3   Institute of Transfusion Medicine and Immunohematology, German Red Cross Blood Transfusion Service Baden-Württemberg – Hessen, Frankfurt, Germany
,
Sixten Körper
1   Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, and, University Hospital Ulm, Ulm, Germany
2   Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
› Institutsangaben

Abstract

COVID-19 convalescent plasma (CCP) has been explored as one of the treatment options for COVID-19. Results of many cohort studies and clinical trials have been recently published. At first glance, the results of the CCP studies appear to be inconsistent. However, it became clear that CCP is not beneficial if CCP with low anti-SARS-CoV-2 antibody concentrations is used, if it is administered late in advanced disease stages, and to patients who already mounted an antibody response against SARS-CoV-2 at the time of CCP transfusion. On the other hand, CCP may prevent progression to severe COVID-19 when very high-titer CCP is given early in vulnerable patients. Immune escape of new variants is a challenge for passive immunotherapy. While new variants of concern developed resistance to most clinically used monoclonal antibodies very rapidly, immune plasma from individuals immunized by both a natural SARS-CoV-2 infection and SARS-CoV-2 vaccination retained neutralizing activity against variants. This review briefly summarizes the evidence on CCP treatment to date and identifies further research needs. Ongoing research on passive immunotherapy is not only relevant for improving care for vulnerable patients in the ongoing SARS-CoV-2 pandemic, but even more as a model for passive immunotherapy in case of future pandemics with a newly evolving pathogen. Compared to other drugs, which must be newly developed in a pandemic (e.g., monoclonal antibodies, antiviral drugs), convalescent plasma is rapidly available, inexpensive to produce, and can be adaptive to viral evolution by selection of contemporary convalescent donors.



Publikationsverlauf

Eingereicht: 28. Oktober 2022

Angenommen: 24. November 2022

Artikel online veröffentlicht:
20. Februar 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Shah V, Ko Ko T, Zuckerman M. et al. Poor outcome and prolonged persistence of SARS-CoV-2 RNA in COVID-19 patients with haematological malignancies; King's College Hospital experience. Br J Haematol 2020; 190 (05) e279-e282
  • 2 Sahu T, Verma HK, Lvks B. Management of SARS-CoV-2 infection is a major challenge in patients with lymphoid malignancies: warrants a clear therapeutic strategy. World J Virol 2022; 11 (04) 204-207
  • 3 Khoury E, Nevitt S, Madsen WR, Turtle L, Davies G, Palmieri C. Differences in outcomes and factors associated with mortality among patients with SARS-CoV-2 infection and cancer compared with those without cancer: a systematic review and meta-analysis. JAMA Netw Open 2022; 5 (05) e2210880
  • 4 Langerbeins P, Hallek M. COVID-19 in patients with hematologic malignancy. Blood 2022; 140 (03) 236-252
  • 5 Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest 2020; 130 (04) 1545-1548
  • 6 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 (06) 2757-2765
  • 7 Tiberghien P, de Lamballerie X, Morel P, Gallian P, Lacombe K, Yazdanpanah Y. Collecting and evaluating convalescent plasma for COVID-19 treatment: why and how?. Vox Sang 2020; 115 (06) 488-494
  • 8 Mair-Jenkins J, Saavedra-Campos M, Baillie JK. et al; 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; 211 (01) 80-90
  • 9 Joyner MJ, Carter RE, Senefeld JW. et al. Convalescent plasma antibody levels and the risk of death from COVID-19. N Engl J Med 2021; 384 (11) 1015-1027
  • 10 US Food and Drug Administration (FDA). FDA issues emergency use authorization for convalescent plasma as potential promising COVID-19 treatment, another achievement in administration's fight against pandemic. Accessed December 10, 2022 at: https://www.Fda.gov/news-events/press-announcements/fda-issuesemergency-use-authorization-convalescentplasma-potential-promising-covid-19-treatment
  • 11 Estcourt LJ, Roberts DJ. Convalescent plasma for COVID-19. BMJ 2020; 370: m3516
  • 12 Tao K, Tzou PL, Kosakovsky Pond SL, Ioannidis JPA, Shafer RW. Susceptibility of SARS-CoV-2 omicron variants to therapeutic monoclonal antibodies: systematic review and meta-analysis. Microbiol Spectr 2022; 10 (04) e0092622
  • 13 McConnell D, Harte M, Walsh C. et al. Comparative effectiveness of neutralising monoclonal antibodies in high risk COVID-19 patients: a Bayesian network meta-analysis. Sci Rep 2022; 12 (01) 17561
  • 14 Jayk Bernal A, Gomes da Silva MM, Musungaie DB. et al; MOVe-OUT Study Group. Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients. N Engl J Med 2022; 386 (06) 509-520
  • 15 Hammond J, Leister-Tebbe H, Gardner A. et al; EPIC-HR Investigators. Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. N Engl J Med 2022; 386 (15) 1397-1408
  • 16 Gottlieb RL, Vaca CE, Paredes R. et al; GS-US-540-9012 (PINETREE) Investigators. Early remdesivir to prevent progression to severe COVID-19 in Outpatients. N Engl J Med 2022; 386 (04) 305-315
  • 17 Focosi D, Franchini M. Passive immunotherapies for COVID-19: The subtle line between standard and hyperimmune immunoglobulins is getting invisible. Rev Med Virol 2022; 32 (04) e2341
  • 18 ITAC (INSIGHT 013) Study Group. Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial. Lancet 2022; 399 (10324): 530-540
  • 19 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 (05) 460-470
  • 20 Estcourt LJ, Turgeon AF, McQuilten ZK. et al; Writing Committee for the REMAP-CAP Investigators. Effect of convalescent plasma on organ support-free days in critically ill patients with COVID-19: a randomized clinical trial. JAMA 2021; 326 (17) 1690-1702
  • 21 Bar KJ, Shaw PA, Choi GH. et al. A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia. J Clin Invest 2021; 131 (24) 131
  • 22 De Santis GC, Oliveira LC, Garibaldi PMM. et al. High-dose convalescent plasma for treatment of severe COVID-19. Emerg Infect Dis 2022; 28 (03) 548-555
  • 23 Agarwal A, Mukherjee A, Kumar G, Chatterjee P, Bhatnagar T, Malhotra P. PLACID Trial Collaborators. 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; 371: m3939
  • 24 Avendano-Sola C, Ramos-Martinez A, Munez-Rubio E. et al. Convalescent plasma for COVID-19: a multicenter, randomized clinical trial. medRxiv 2020:2020.08.26.20182444
  • 25 AlQahtani M, Abdulrahman A, Almadani A. et al. Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease. Sci Rep 2021; 11 (01) 9927
  • 26 Simonovich VA, Burgos Pratx LD, Scibona P. et al; PlasmAr Study Group. A randomized trial of convalescent plasma in COVID-19 severe pneumonia. N Engl J Med 2021; 384 (07) 619-629
  • 27 Holm K, Lundgren MN, Kjeldsen-Kragh J. et al. Convalescence plasma treatment of COVID-19: results from a prematurely terminated randomized controlled open-label study in Southern Sweden. BMC Res Notes 2021; 14 (01) 440
  • 28 Menichetti F, Popoli P, Puopolo M. et al; TSUNAMI Study Group. Effect of high-titer convalescent plasma on progression to severe respiratory failure or death in hospitalized patients with COVID-19 pneumonia: a randomized clinical trial. JAMA Netw Open 2021; 4 (11) e2136246
  • 29 Kirenga B, Byakika-Kibwika P, Muttamba W. et al. Efficacy of convalescent plasma for treatment of COVID-19 in Uganda. BMJ Open Respir Res 2021; 8 (01) 8
  • 30 Korley FK, Durkalski-Mauldin V, Yeatts SD. et al; SIREN-C3PO Investigators. Early convalescent plasma for high-risk outpatients with COVID-19. N Engl J Med 2021; 385 (21) 1951-1960
  • 31 Gharbharan A, Jordans CCE, Geurtsvankessel C. et al. Convalescent plasma for COVID-19. A randomized clinical trial. medRxiv 2020:2020.10.25.20219337
  • 32 Ray Y, Paul SR, Bandopadhyay P. et al. Clinical and immunological benefits of convalescent plasma therapy in severe COVID-19: insights from a single center open label randomised control trial. medRxiv 2020; 16957608
  • 33 Devos T, Van Thillo Q, Compernolle V. et al; DAWn-Plasma Investigators. Early high antibody titre convalescent plasma for hospitalised COVID-19 patients: DAWn-plasma. Eur Respir J 2022; 59 (02) 2101724
  • 34 Ortigoza MB, Yoon H, Goldfeld KS. et al; CONTAIN COVID-19 Consortium for the CONTAIN COVID-19 Study Group. Efficacy and safety of COVID-19 convalescent plasma in hospitalized patients: a randomized clinical trial. JAMA Intern Med 2022; 182 (02) 115-126
  • 35 Körper S, Weiss M, Zickler D. et al; CAPSID Clinical Trial Group. Results of the CAPSID randomized trial for high-dose convalescent plasma in patients with severe COVID-19. J Clin Invest 2021; 131 (20) e152264
  • 36 Sekine L, Arns B, Fabro BR. et al; PLACOVID Study Group. Convalescent plasma for COVID-19 in hospitalised patients: an open-label, randomised clinical trial. Eur Respir J 2022; 59 (02) 2101471
  • 37 Bégin P, Callum J, Jamula E. et al; CONCOR-1 Study Group. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial. Nat Med 2021; 27 (11) 2012-2024
  • 38 RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet 2021; 397 (10289): 2049-2059
  • 39 Balcells ME, Rojas L, Le Corre N. et al. Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: a randomized phase II clinical trial. PLoS Med 2021; 18 (03) e1003415
  • 40 O'Donnell MR, Grinsztejn B, Cummings MJ. et al. A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19. J Clin Invest 2021; 131 (13) e150646
  • 41 Bajpai M, Maheshwari A, Dogra V. et al. Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial). BMJ Open 2022; 12 (04) e055189
  • 42 Thorlacius-Ussing L, Brooks PT, Nielsen H. et al. A randomized placebo-controlled trial of convalescent plasma for adults hospitalized with COVID-19 pneumonia. Sci Rep 2022; 12 (01) 16385
  • 43 van den Berg K, Glatt TN, Vermeulen M. et al. Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial). Sci Rep 2022; 12 (01) 2552
  • 44 Libster R, Marc GPR, Wappner D. et al. Prevention of severe COVID-19 in the elderly by early high-titer plasma. medRxiv 2020; DOI: 10.1101/2020.11.20.20234.
  • 45 Sullivan DJ, Gebo KA, Shoham S. et al. Early outpatient treatment for COVID-19 with convalescent plasma. N Engl J Med 2022; 386 (18) 1700-1711
  • 46 Millat-Martinez P, Gharbharan A, Alemany A. et al; CoV-Early Study Group, COnV-ert Study Group. Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients. Nat Commun 2022; 13 (01) 2583
  • 47 Alemany A, Millat-Martinez P, Corbacho-Monné M. et al; CONV-ERT Group. High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial. Lancet Respir Med 2022; 10 (03) 278-288
  • 48 Gharbharan A, Jordans C, Zwaginga L. et al; CoV-Early Study Group. Outpatient convalescent plasma therapy for high-risk patients with early COVID-19: a randomized placebo-controlled trial. Clin Microbiol Infect 2022:S1198-743X(22)00421-9
  • 49 Estcourt LJ, Cohn CS, Pagano MB. et al. Clinical practice guidelines from the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 convalescent plasma. Ann Intern Med 2022; 175 (09) 1310-1321
  • 50 Klassen SA, Senefeld JW, Johnson PW. et al. Evidence favoring the efficacy of convalescent plasma for COVID-19 therapy. medRxiv 2020; DOI: 10.1101/2020.07.29.20162917.
  • 51 de Candia P, Prattichizzo F, Garavelli S. et al. Effect of time and titer in convalescent plasma therapy for COVID-19. iScience 2021; 24 (08) 102898
  • 52 Libster R, Pérez Marc G, Wappner D. et al; Fundación INFANT–COVID-19 Group. Early high-titer plasma therapy to prevent severe COVID-19 in older adults. N Engl J Med 2021; 384 (07) 610-618
  • 53 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 (01) 3189
  • 54 Nguyen D, Simmonds P, Steenhuis M. et al. SARS-CoV-2 neutralising antibody testing in Europe: towards harmonisation of neutralising antibody titres for better use of convalescent plasma and comparability of trial data. Euro Surveill 2021; 26 (27) 26
  • 55 Wouters E, Steenhuis M, Schrezenmeier H. et al. Evaluation of SARS-CoV-2 antibody titers and potency for convalescent plasma donation: a brief commentary. Vox Sang 2021; 116 (05) 493-496
  • 56 Weinreich DM, Sivapalasingam S, Norton T. et al; Trial Investigators. REGEN-COV antibody combination and outcomes in outpatients with COVID-19. N Engl J Med 2021; 385 (23) e81
  • 57 Rijnders BJA, Huygens S, Mitjà O. Evidence-based dosing of convalescent plasma for COVID-19 in future trials. Clin Microbiol Infect 2022; 28 (05) 667-671
  • 58 Körper S, Grüner B, Zickler D. et al. One-year follow-up of the CAPSID randomized trial for high-dose convalescent plasma in severe COVID-19 patients. J Clin Invest 2022; e163657
  • 59 Salazar E, Perez KK, Ashraf M. et al. Treatment of coronavirus disease 2019 (COVID-19) patients with convalescent plasma. Am J Pathol 2020; 190 (08) 1680-1690
  • 60 Marconato M, Abela IA, Hauser A. et al. Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response. J Clin Invest 2022; 132 (12) e158190
  • 61 Horby PW, Estcourt L, Eto L. et al. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. medRxiv 2021:2020.06.22.20137273
  • 62 Avendaño-Solá C, Ramos-Martínez A, Muñez-Rubio E. et al; ConPlas-19 Study Group. A multicenter randomized open-label clinical trial for convalescent plasma in patients hospitalized with COVID-19 pneumonia. J Clin Invest 2021; 131 (20) e152740
  • 63 Aydillo T, Gonzalez-Reiche AS, Aslam S. et al. Shedding of viable SARS-CoV-2 after immunosuppressive therapy for cancer. N Engl J Med 2020; 383 (26) 2586-2588
  • 64 DeWolf S, Laracy JC, Perales MA, Kamboj M, van den Brink MRM, Vardhana S. SARS-CoV-2 in immunocompromised individuals. Immunity 2022; 55 (10) 1779-1798
  • 65 Shah V, Ko Ko T, Zuckerman M. et al. Poor outcome and prolonged persistence of SARS-CoV-2 RNA in COVID-19 patients with haematological malignancies; King's College Hospital experience. Br J Haematol 2020; 190 (05) e279-e282
  • 66 Thompson MA, Henderson JP, Shah PK. et al; COVID-19 and Cancer Consortium. Association of convalescent plasma therapy with survival in patients with hematologic cancers and COVID-19. JAMA Oncol 2021; 7 (08) 1167-1175
  • 67 Hueso T, Godron AS, Lanoy E. et al. Convalescent plasma improves overall survival in patients with B-cell lymphoid malignancy and COVID-19: a longitudinal cohort and propensity score analysis. Leukemia 2022; 36 (04) 1025-1034
  • 68 Biernat MM, Kolasińska A, Kwiatkowski J. et al. Early administration of convalescent plasma improves survival in patients with hematological malignancies and COVID-19. Viruses 2021; 13 (03) 13
  • 69 Lanza F, Monaco F, Ciceri F. et al. Lack of efficacy of convalescent plasma in COVID-19 patients with concomitant hematological malignancies: an Italian retrospective study. Hematol Oncol 2022
  • 70 Cristelli MP, Langhi Junior DM, Viana LA. et al. Efficacy of convalescent plasma to treat mild to moderate COVID-19 in kidney transplant patients: a propensity score matching analysis. Transplantation 2022; 106 (01) e92-e94
  • 71 Müller-Tidow C, Janssen M, Schäkel U. et al. A randomized controlled clinical trial demonstrates that plasma from convalescent and vaccinated donors improves outcome of COVID-19 in patients with hematological disease, cancer or immunosuppression. [abstract]. EHA Library 2022; 357146
  • 72 Lacombe K, Hueso T, Porcher R. et al. Efficacy and safety of convalescent plasma to treat hospitalised COVID-19 patients with or without underlying immunodeficiency: a randomized clinical trial. medRxiv 2022; http://medrxiv.org/content/early/2022/08/10/2022.08.09.22278329.abstract:2022
  • 73 Senefeld JW, Franchini M, Mengoli C. et al. COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review. medRxiv 2022;2022
  • 74 Wang Z, Muecksch F, Schaefer-Babajew D. et al. Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection. Nature 2021; 595 (7867): 426-431
  • 75 Lustig Y, Nemet I, Kliker L. et al. Neutralizing response against variants after SARS-CoV-2 infection and one dose of BNT162b2. N Engl J Med 2021; 384 (25) 2453-2454
  • 76 Stamatatos L, Czartoski J, Wan YH. et al. mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection. Science 2021; 372 (6549): 1413-1418
  • 77 Rössler A, Riepler L, Bante D, von Laer D, Kimpel J. SARS-CoV-2 omicron variant neutralization in serum from vaccinated and convalescent persons. N Engl J Med 2022; 386 (07) 698-700
  • 78 Wilhelm A, Widera M, Grikscheit K. et al. Limited neutralisation of the SARS-CoV-2 omicron subvariants BA.1 and BA.2 by convalescent and vaccine serum and monoclonal antibodies. EBioMedicine 2022; 82: 104158
  • 79 Liu L, Iketani S, Guo Y. et al. Striking antibody evasion manifested by the omicron variant of SARS-CoV-2. Nature 2022; 602 (7898): 676-681
  • 80 Planas D, Saunders N, Maes P. et al. Considerable escape of SARS-CoV-2 omicron to antibody neutralization. Nature 2022; 602 (7898): 671-675
  • 81 Cameroni E, Bowen JE, Rosen LE. et al. Broadly neutralizing antibodies overcome SARS-CoV-2 omicron antigenic shift. Nature 2022; 602 (7898): 664-670
  • 82 Seidel A, Jahrsdörfer B, Körper S. et al. SARS-CoV-2 vaccination of convalescents boosts neutralization capacity against SARS-CoV-2 delta and omicron that can be predicted by anti-S antibody concentrations in serological assays. medRxiv 2022; http://medrxiv.org/content/early/2022/01/17/2022.01.17.22269201
  • 83 Nguyen D, Simmonds P, Steenhuis M. et al. SARS-CoV-2 neutralising antibody testing in Europe: towards harmonisation of neutralising antibody titres for better use of convalescent plasma and comparability of trial data. Euro Surveill 2021; 26 (27) 26