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

Vox Sang. 2021 Jul;116(6):665-672. doi: 10.1111/vox.13056. Epub 2021 Mar 18.

Abstract

Background and objectives: COVID-19 convalescent plasma is an experimental treatment against SARS-CoV-2. The aim of this study is to assess the impact of different pathogen reduction methods on the levels and virus neutralizing activity of the specific antibodies against SARS-CoV2 in convalescent plasma.

Materials and methods: A total of 140 plasma doses collected by plasmapheresis from COVID-19 convalescent donors were subjected to pathogen reduction by three methods: methylene blue (M)/visible light, riboflavin (R)/UVB and amotosalen (A)/UVA. To conduct a paired comparison, individual plasma doses were divided into 2 samples that were subjected to one of these methods. 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: The methods reduced NtAbs titres differently: among units with the initial titre 80 or above, 81% of units remained unchanged and 19% decreased by one step after methylene blue; 60% were unchanged and 40% decreased by one step after amotosalen; after riboflavin 43% were unchanged and 50% (7%, respectively) had a one-step (two-step, respectively) decrease. Paired two-sample comparisons (M vs. A, M vs. R and A vs. R) revealed that the largest statistically significant decrease in quantity and activity of the specific antibodies resulted from the riboflavin treatment.

Conclusion: Pathogen reduction with methylene blue or with amotosalen provides the greater likelihood of preserving the immunological properties of the COVID-19 convalescent plasma compared to riboflavin.

Keywords: COVID-19 convalescent plasma; NtAbs; amotosalen; methylene blue; pathogen reduction; riboflavin.

MeSH terms

  • Antibodies, Neutralizing / blood
  • Blood Safety / methods*
  • Blood-Borne Pathogens / isolation & purification*
  • COVID-19 / immunology
  • COVID-19 / therapy*
  • COVID-19 Serotherapy
  • Furocoumarins
  • Humans
  • Immunization, Passive
  • Methylene Blue
  • Plasma / immunology*
  • Riboflavin
  • SARS-CoV-2 / immunology

Substances

  • Antibodies, Neutralizing
  • Furocoumarins
  • amotosalen
  • Methylene Blue
  • Riboflavin