Impact of pathogen reduction methods on immunological properties of the COVID-19 convalescent plasma

Abstract

Background and Objectives In the absence of a vaccine or specific antiviral drugs against SARS-CoV-2 COVID-19 convalescent plasma became one of the experimental treatment options in many countries. Aim of this study was to assess the impact of different pathogen reduction technologies on the immunological properties of COVID-19 convalescent plasma. Materials and Methods In our experiment 140 doses of plasma collected by plasmapheresis from COVID-19 convalescent donors were subjected to pathogen reduction with one of three different methods: methylene blue (M), riboflavin (R), and amotosalen (A). To conduct a paired two-sample comparison each plasma dose was divided into 2 that were treated by one of these technologies. The titres of SARS-CoV2 neutralizing antibodies (NtAbs) and levels of specific immunoglobulins to RBD, S- and N- proteins of SARS-CoV-2 were measured before and after pathogen reduction. Results All methods reduced NtAbs titers significantly but not at the same grade: among units with the initial titre 80 or above, 81% of units had unchanged titres while 19% decreased by 1 step after methylene blue; 60% unchanged and 40% - decreased by 1 step after amotosalen; 43% unchanged, 67% a one-step decrease and 6% - a two-step decrease after riboflavin. Pairwise two-sample comparisons (M vs A, M vs R and A vs R) revealed the most prominent and statistically significant decrease in all studied parameters (except anti-RBD) following pathogen reduction with riboflavin. Conclusion Pathogen reduction with amotosalen and methylene blue provides the greater likelihood of preserving the immunological properties of the COVID-19 convalescent plasma compared to riboflavin.

High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial

“…Methylene blue is a method of pathogen inactivation for plasma that is widely used in some countries in Europe. A study from Russia showed that some units of plasma lost neutralising activity with methylene blue inactivation, 34 whereas other studies found no difference. 35,36 We analysed the neutralising activity of stored donor samples (ie, before methylene blue treatment) compared with the plasma unit (ie, after methylene blue treatment) in a subgroup of plasma units and we found no differences in neutralising antibody titres (median ID50 1:1256 [IQR 1:709-1:2712] vs 1:1287 [1:349-1:3333]; p=0•32).…”

Efficacy of early transfusion of convalescent plasma with high‐titer SARS‐CoV‐2 neutralizing antibodies in hospitalized patients with COVID‐19

“…Prior studies have shown that photoinactivation with methylene blue does not significantly reduce the titers of SARS-CoV-2 antibodies. [36][37] In fact, the methylene blue method has been reported to be less detrimental to anti-SARS-CoV2-2 titers than other pathogen-reduction technologies currently applied to donated plasma. 36 However, we cannot certainly disregard some decrease in the in vivo neutralizing capacity due to pathogen-reduction.…”

“…Donor CCP was submitted to pathogen‐reduction to minimize the hypothetical risk of SARS‐CoV‐2 transmission and comply with the Spanish Government requirements for plasma transfusion. Prior studies have shown that photoinactivation with methylene blue does not significantly reduce the titers of SARS‐CoV‐2 antibodies 36–37 . In fact, the methylene blue method has been reported to be less detrimental to anti‐SARS‐CoV2‐2 titers than other pathogen‐reduction technologies currently applied to donated plasma 36 .…”

Methylene Blue Inhibits the Interaction Between Heparan Sulfate and Sars-Cov-2 Spike Protein; A Review of Evidence for a Hypothesis.

“…In line with the aforementioned findings, heparan sulfatehas been recognized as an important attachment factor for SARS-CoV-2 infection in human lung damage, hyper-inflammatory reaction, etc (Pardo Andreu, 2021). Moreover, MB has other potential applications in the COVID-19 pandemic, including decontamination of personal protective equipment (Lendvay et al, 2021), and pathogen reduction of COVID-19 convalescent plasma (Kostin et al, 2021). Additionally, some studies suggest the prospective use of photodynamic therapy as an effective method for the prevention and treatment of COVID-19 (Svyatchenko et al, 2021).…”