tetano
Editor, Senior Moderator
PLoS One
. 2020 Dec 22;15(12):e0243967.
doi: 10.1371/journal.pone.0243967. eCollection 2020.
Manufacturing of convalescent plasma of COVID-19 patients: Aspects of quality
Viola H?hnel[SUP] 1 [/SUP], David Peterhoff[SUP] 2 [/SUP], Veronika B?uerlein[SUP] 1 [/SUP], Andreas-Michael Brosig[SUP] 1 [/SUP], Irene Pamler[SUP] 1 [/SUP], Christian Johnson[SUP] 1 [/SUP], Adelina Bica[SUP] 1 [/SUP], Monica Totir[SUP] 1 [/SUP], Thomas Ossner[SUP] 1 [/SUP], Barbara Stemmer[SUP] 1 [/SUP], Martina Toelge[SUP] 2 [/SUP], Anja Sch?tz[SUP] 2 [/SUP], Hans-Helmut Niller[SUP] 2 3 [/SUP], Barbara Schmidt[SUP] 2 3 [/SUP], Ralf Wagner[SUP] 2 3 [/SUP], Andr? Gessner[SUP] 2 3 [/SUP], Ralph Burkhard[SUP] 1 [/SUP], Robert Offner[SUP] 1 [/SUP]
Affiliations
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.
. 2020 Dec 22;15(12):e0243967.
doi: 10.1371/journal.pone.0243967. eCollection 2020.
Manufacturing of convalescent plasma of COVID-19 patients: Aspects of quality
Viola H?hnel[SUP] 1 [/SUP], David Peterhoff[SUP] 2 [/SUP], Veronika B?uerlein[SUP] 1 [/SUP], Andreas-Michael Brosig[SUP] 1 [/SUP], Irene Pamler[SUP] 1 [/SUP], Christian Johnson[SUP] 1 [/SUP], Adelina Bica[SUP] 1 [/SUP], Monica Totir[SUP] 1 [/SUP], Thomas Ossner[SUP] 1 [/SUP], Barbara Stemmer[SUP] 1 [/SUP], Martina Toelge[SUP] 2 [/SUP], Anja Sch?tz[SUP] 2 [/SUP], Hans-Helmut Niller[SUP] 2 3 [/SUP], Barbara Schmidt[SUP] 2 3 [/SUP], Ralf Wagner[SUP] 2 3 [/SUP], Andr? Gessner[SUP] 2 3 [/SUP], Ralph Burkhard[SUP] 1 [/SUP], Robert Offner[SUP] 1 [/SUP]
Affiliations
- PMID: 33351831
- DOI: 10.1371/journal.pone.0243967
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.