Stability and neutralising capacity of SARS-CoV-2-specific antibodies in convalescent plasma (2020)

Convalescent plasma is a promising therapeutic strategy that might have benefit in patients with COVID-19,1Shen C Wang Z Zhao F et al.Treatment of 5 critically ill patients with COVID-19 with convalescent Plasma.JAMA. 2020; 323: 1582-1589Crossref PubMed Scopus (1686) Google Scholar, 2Duan K Liu B Li C et al.Effectiveness of convalescent plasma therapy in severe COVID-19 patients.PNAS. 2020; 117: 9490-9496Crossref PubMed Scopus (1358) Google Scholar despite unproven safety and efficacy. Although randomised clinical trials are ongoing, decision making with regard to the transfusion of convalescent plasma from patients who have recovered from COVID-19 should follow a risk-based approach, whereby the potential risks are minimised in favour of not yet proven therapeutic benefits. WHO Blood Regulators Network and several other stakeholders, such as the International Society of Blood Transfusion, recommend risk mitigation for transfusion-transmissible disease through pathogen inactivation.3WHO Blood Regulators NetworkPosition paper on use of convalescent plasma, serum or immune globulin concentrates as an element in response to an emerging virus.https://www.who.int/bloodproducts/brn/2017_BRN_PositionPaper_ConvalescentPlasma.pdf?ua=1Date: 2017Date accessed: May 15, 2020Google Scholar, 4Epstein J Burnouf T Points to consider in the preparation and transfusion of COVID-19 convalescent plasma.https://isbtweb.org/fileadmin/user_upload/Points_to_consider_in_the_preparation_of_COVID_convalescent_plasma_-_200331_ISBT_WP_GBS_Final.pdfDate accessed: May 15, 2020Google Scholar However, at present no data exist regarding the effect of pathogen-inactivation methods or cryopreservation on the stability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibodies. We therefore analysed the effect of psoralen and ultraviolet light pathogen inactivation (Intercept Blood System; Cerus, Concord, CA USA) on the total SARS-CoV-2 IgG titre (IgG ELISA; Euroimmun, Lubeck, Germany) and neutralising capacity (life virus assay)5Wölfel R Corman VM Guggemos W et al.Virological assessment of hospitalized patients with COVID-2019.Nature. 2020; (published online April 1.)DOI:10.1038/s41586-020-2196-xCrossref PubMed Scopus (4499) Google Scholar in convalescent plasma obtained from patients who have recovered from COVID-19. Our data show that pathogen inactivation of convalescent plasma does not impair the stability and neutralising capacity of SARS-CoV-2-specific antibodies compared with non-pathogen-inactivated controls. Although SARS-CoV-2 IgG titre and neutralising capacity seem to correlate, initial observations from our ongoing convalescent plasma programme at University Hospital Carl-Gustav Carus (Dresden, Germany) have shown that some individual cases have moderate neutralising capacity despite high anti-SARS-CoV-2-IgG titres (appendix). The stability of SARS-CoV-2 IgG and the overall neutralising capacity was also preserved at 100% when the plasma was shock frozen at −30°C after pathogen-inactivation (appendix) or stored as liquid plasma for up to 9 days (data not shown). Our data suggest that pathogen-inactivation of convalescent plasma from patients who have recovered from COVID-19 does not alter the potential therapeutic potency and should be recommended to mitigate the risk for transfusion associated viral transmission. Considering the currently unproven clinical benefit of convalescent plasma obtained from patients who have had COVID-19, a shift in the risk–benefit ratio towards benefit by means of pathogen-inactivation should be employed in all cases, in settings where the use of pathogen inactivation methods are available and established. We declare no competing interests. Download .pdf (.2 MB) Help with pdf files Supplementary appendix