Antibody profiles in COVID‐19 convalescent plasma prepared with amotosalen/UVA pathogen reduction treatment

Abstract

Background COVID‐19 convalescent plasma (CCP), from donors recovered from severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection, is one of the limited therapeutic options currently available for the treatment of critically ill patients with COVID‐19. There is growing evidence that CCP may reduce viral loads and disease severity; and reduce mortality. However, concerns about the risk of transfusion‐transmitted infections (TTI) and other complications associated with transfusion of plasma, remain. Amotosalen/UVA pathogen reduction treatment (A/UVA‐PRT) of plasma offers a mitigation of TTI risk, and when combined with pooling has the potential to increase the diversity of the polyclonal SARS‐CoV‐2 neutralizing antibodies. Study design and methods This study assessed the impact of A/UVA‐PRT on SARS‐CoV‐2 antibodies in 42 CCP using multiple complimentary assays including antigen binding, neutralizing, and epitope microarrays. Other mediators of CCP efficacy were also assessed. Results A/UVA‐PRT did not negatively impact antibodies to SARS‐CoV‐2 and other viral epitopes, had no impact on neutralizing activity or other potential mediators of CCP efficacy. Finally, immune cross‐reactivity with other coronavirus antigens was observed raising the potential for neutralizing activity against other emergent coronaviruses. Conclusion The findings of this study support the selection of effective CCP combined with the use of A/UVA‐PRT in the production of CCP for patients with COVID‐19.

Characterization of pathogen‐inactivated COVID‐19 convalescent plasma and responses in transfused patients

“…All five antibody assays indicated no significant impact by PRT consistent with recent observations in a larger data set of dCCP. 67 Specifically, reactivity against the S protein using the ADAP S1 Ab assay and virus neutralization efficacy using two different assays (RVPN NT 50 and ACE‐2 blocking nAb) were unaffected by PRT.…”

“…Based on plasma samples from healthy control donors prior to COVID‐19, the negative cutoff (∆ C t ) values for S1, N, and ACE inhibitors were respectively: 1.5, 4.0, and 0.4. These assays have been used in a larger dCCP data set recently reported 67 …”

Pathogen reduction technologies need to evaluate Fc‐mediated antibody functions

“…The authors have disclosed no conflicts of interest. Daniele Focosi 1 Arturo Casadevall 2 1 North-Western Tuscany Blood Bank, Pisa University Hospital, Pisa, Italy…”

“…The letter of Focosi and Casadevall raises the interesting question of the functionality of the Fc portion of antibodies to SARS-CoV-2 in pathogen reduced COVID convalescent plasma (CCP) with reference to our study of CCP antibody profiles. 1 They note that antibodydependent cellular cytotoxicity (ADCC) and antibodydependent cellular phagocytosis (ADCP) may be important for the clearance of SARS-CoV-2 in infected patients and for disease resolution. Our study focused on the characteristics of antibodies to the S and the N proteins of SARS-CoV-2 using multiple complimentary assays to characterize the neutralization of infectivity targeting the ACE-2 receptor.…”

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Dear Editor, We read with interest the recent article by Bagri et al reporting no detrimental effects of Intercept ® on anti-SARS-CoV-2 antibodies in COVID-19 convalescent plasma (CCP) in terms of antigen binding, neutralizing, and epitope microarrays. 1 We commend the investigators for the careful work done in their study. Such findings are reassuring and needed, since the various pathogen-reduced plasma went through clinical evaluation to assess their hemostatic activity linked to coagulation factors, or, at best, Fc binding to receptors, not their immunological activity.

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