Manufacturing of convalescent plasma of COVID-19 patients: Aspects of quality

PLoS One. 2020 Dec 22;15(12):e0243967. doi: 10.1371/journal.pone.0243967. eCollection 2020.

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic emerged in December 2019. Convalescent plasma represents a promising COVID-19 treatment. Here, we report on the manufacturing of a plasma-based product containing antibodies specific to SARS-CoV-2 obtained from recently recovered COVID-19 patients. Convalescent plasma donors were screened as follows: 1) previously confirmed SARS-CoV-2 infection (by real-time PCR (RT-PCR)); 2) a subsequent negative PCR test followed by a 2-week waiting period; 3) an additional negative PCR test prior to plasmapheresis; and 4) confirmation of the presence of SARS-CoV-2 specific antibodies. Convalescent plasma was stored fresh (2-6°C) for up to 5 days or frozen (-30°C) for long-term storage. Donor peripheral blood and final plasma product were assayed for binding antibodies targeting the SARS-CoV-2 S-protein receptor-binding domain (RBD) and their titers measured by an enzyme-linked immunosorbent assay (ELISA). We performed 72 plasmaphereses resulting in 248 final products. Convalescent plasma contained an RBD-specific antibody titer (IgG) ranging from 1:100 to 1:3200 (median 1:800). The titer was congruent to the titer of the blood (n = 34) before collection (1:100-1:6400, median 1:800). Levels of IL-8 and LBP of donors were slightly increased. Therapeutic products derived from a human origin must undergo rigorous testing to ensure uniform quality and patient safety. Whilst previous publications recommended RBD-specific binding antibody titers of ≥ 1:320, we selected a minimum titer of 1:800 in order to maximize antibody delivery. Production of highly standardized convalescent plasma was safe, feasible and was readily implemented in the treatment of severely ill COVID-19 patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology
  • COVID-19 / blood
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • COVID-19 / therapy*
  • COVID-19 / virology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunization, Passive
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Male
  • Middle Aged
  • Neutralization Tests
  • Pandemics
  • Plasma / immunology
  • Plasma / virology
  • Plasmapheresis / methods
  • SARS-CoV-2 / immunology
  • Tissue Donors
  • Young Adult

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulin M

Supplementary concepts

  • COVID-19 serotherapy

Grant support

The authors acknowledge financial support through the pandemic responsiveness of The Bavarian Ministry of Science and Art. DP, AS were funded by project EHVA (H2020, Grant 681032 to RW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.