ABSTRACT
Background: COVID-19 convalescent plasma (CCP) was shown to reduce disease progression if high-titre CCP is administered in early infection. CCP donors have a risk profile like first time donors, especially with respect to window-period viral transmissions. Pathogen reduction (PR) could mitigate that risk, but may have impact on quality and quantity of plasma proteins, including neutralizing antibodies. It has been shown that different IgG subclasses contribute differently to CCP neutralizing activity, raising the question of a potential impact of PR on different IgG subclasses. Aims: Side-by-side comparison of the impact of 3 commercially available PR technologies on total IgG and subclasses quantity and subclass distribution in CCP. Methods: 36 apheresis CCP donations collected with a MCS+ 9000 plasmapheresis device (Haemonetics S.A., Switzerland), or DigiPla 80 (Sichuan Nigale Biomed, China) plasmapheresis device (650-750 ml) were allocated to 3 study groups with 12 units respectively. The impact of amotosalen/UVA (AS)-treatment (INTERCEPT Blood System, Cerus) against Riboflavin UVB (RB) (Mirasol Pathogen Reduction System, Terumo BCT), AS against Methylene Blue (MB) (Theraflex MB, Macopharma) and RB against MB on the quantity and distribution of IgG and subclasses was assessed in a side-by-side comparison study with a nephelometric analyser (BN II System, Siemens Healthcare). PRtreatment was conducted immediately post collection. All samples for analysis were frozen within 6 h post collection and stored at -75°C until testing. All samples were analysed simultaneously with the same device, the same lot of reagents and the same operator. Results: IgG subclass distributions were not significantly changed post PR-treatment with all 3 technologies (p > 0.05). There was also no significant difference in the median loss of concentration for IgG1 and IgG2 between the three technologies (p > 0.05). The median loss (%) of IgG3 (2.1 and 2.6-fold compared to AS and MBtreatment respectively, p < 0.01) and IgG4 (1.6 and 5.9-fold compared to AS and MB-treatment respectively, p < 0.01) post RBtreatment was significantly higher. The median loss (%) of IgG4 post AS-treatment was significantly higher compared to MB-treatment (3.5-fold, p < 0.01). Summary/Conclusions: The 3 commercially available PR systems do not significantly change the IgG subclass distribution, but impact differently IgG3 and IgG4 post-treatment loss. It was reported that IgG1 and IgG3 play an important role in neutralization, which should be considered when planning PR-treatment for CCP. .