Evidence-based dosing of convalescent plasma for COVID-19 in future trials

Bart J.A. Rijnders*, Sammy Huygens, Oriol Mitjà

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

Background: Two years into the pandemic, convincing evidence in favour of convalescent plasma (ConvP) as a treatment for coronavirus disease 2019 (COVID-19) is still lacking. This contrasts sharply with the efficacy of potent virus-neutralizing monoclonal antibodies. However, resistance of the Omicron variant against almost all licensed monoclonals turns back the clock, and we can expect that ConvP will regain interest. Indeed, the efficacy of virus-neutralizing monoclonal antibodies supports the premise that ConvP will work when used at the right time, at the right dose, and containing antibodies with the right affinity. Objectives: This study aimed to review available evidence on dosing of ConvP for COVID-19 and provide guidance for future trials or patient care. Sources: Because no dose-finding human trials were ever performed, we reviewed COVID-19 animal model studies and human trials that provide (in)direct data on the pharmacokinetics and pharmacodynamics of ConvP. We also discuss the identification of appropriate ConvP donors in the context of emerging severe acute respiratory syndrome coronavirus 2 variants. Content: Compared with dosing in animal studies, almost all human trials used substantially lower doses. Identifying donors with sufficiently high virus-neutralizing antibody titres is challenging, in particular when new variants escape immunity induced by ancestral variants. Ways to avoid underdosing are (a) use of ConvP from two different donors, (b) use only ConvP known to neutralize the variant with which the patient is infected, (c) use two ConvP units with a neutralizing antibody titre ≥1/1250 (when only one plasma unit is available, neutralizing antibody titre of ≥1/2500 is recommended), (d) use an antibody test that correlates well with virus neutralization (use of international units per ml (IU/ml) for virus neutralization is strongly encouraged), and (e) use of donors shortly after a third mRNA vaccination may simplify the donor selection process. Implications: In future trials on ConvP for COVID-19, more stringent donor selection criteria and/or higher volume transfusions should be used.

Original languageEnglish
Pages (from-to)667-671
Number of pages5
JournalClinical Microbiology and Infection
Volume28
Issue number5
Early online date9 Feb 2022
DOIs
Publication statusPublished - May 2022

Bibliographical note

Funding Information:
Bart Rijnders received funding from ZonMw (Dutch financing organization for innovation and research in health sciences) under project numbers 10430062010002 and 10430062010001. Sammy Huygens and Oriol Mitjà have no conflicts of interest to declare.

Publisher Copyright:
© 2022 The Author(s)

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