Inactivation of three emerging viruses - severe acute respiratory syndrome coronavirus, Crimean-Congo haemorrhagic fever virus and Nipah virus - in platelet concentrates by ultraviolet C light and in plasma by methylene blue plus visible light

Markus Eickmann, Ute Gravemann, Wiebke Handke, Frank Tolksdorf, Stefan Reichenberg, Thomas H Müller, Axel Seltsam, Markus Eickmann, Ute Gravemann, Wiebke Handke, Frank Tolksdorf, Stefan Reichenberg, Thomas H Müller, Axel Seltsam

Abstract

Background: Emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV), Crimean-Congo haemorrhagic fever virus (CCHFV) and Nipah virus (NiV) have been identified to pose a potential threat to transfusion safety. In this study, the ability of the THERAFLEX UV-Platelets and THERAFLEX MB-Plasma pathogen inactivation systems to inactivate these viruses in platelet concentrates and plasma, respectively, was investigated.

Materials and methods: Blood products were spiked with SARS-CoV, CCHFV or NiV, and then treated with increasing doses of UVC light (THERAFLEX UV-Platelets) or with methylene blue (MB) plus increasing doses of visible light (MB/light; THERAFLEX MB-Plasma). Samples were taken before and after treatment with each illumination dose and tested for residual infectivity.

Results: Treatment with half to three-fourths of the full UVC dose (0·2 J/cm2 ) reduced the infectivity of SARS-CoV (≥3·4 log), CCHFV (≥2·2 log) and NiV (≥4·3 log) to the limit of detection (LOD) in platelet concentrates, and treatment with MB and a fourth of the full light dose (120 J/cm2 ) decreased that of SARS-CoV (≥3·1 log), CCHFV (≥3·2 log) and NiV (≥2·7 log) to the LOD in plasma.

Conclusion: Our study demonstrates that both THERAFLEX UV-Platelets (UVC) and THERAFLEX MB-Plasma (MB/light) effectively reduce the infectivity of SARS-CoV, CCHFV and NiV in platelet concentrates and plasma, respectively.

Keywords: methylene blue; pathogen inactivation; plasma; platelet concentrates; ultraviolet light.

Conflict of interest statement

FT and SR are employees of Macopharma, manufacturer and distributor of the THERAFLEX pathogen inactivation (PI) system. UG, WH, THM and AS received project grants from the German Red Cross Blood Services and Macopharma for the development of the UVC‐based PI technology for platelets. ME has no conflicts of interest to disclose.

© 2020 International Society of Blood Transfusion.

References

    1. Stramer SL, Hollinger FB, Katz LM, et al: Emerging infectious disease agents and their potential threat to transfusion safety. Transfusion 2009; 49:1S–29S
    1. Stramer SL: Current perspectives in transfusion‐transmitted infectious diseases: emerging and re‐emerging infections. ISBT Sci Ser 2014; 9:30–6
    1. Bahar B, Schulz WL, Gokhale A, et al: Blood utilisation and transfusion reactions in adult patients transfused with conventional or pathogen‐reduced platelets. Br J Haematol 2019. 10.1111/bjh.16187 [Epub ahead of print].
    1. Seltsam A, Muller TH: Update on the use of pathogen‐reduced human plasma and platelet concentrates. Br J Haematol 2013; 162:442–54
    1. Mohr H, Steil L, Gravemann U, et al: A novel approach to pathogen reduction in platelet concentrates using short‐wave ultraviolet light. Transfusion 2009; 49:2612–24
    1. Seltsam A, Muller TH: UVC irradiation for pathogen reduction of platelet concentrates and plasma. Transfus Med Hemother 2011; 38:43–54
    1. Kim S, Handke W, Gravemann U, et al: Mitochondrial DNA multiplex real‐time polymerase chain reaction inhibition assay for quality control of pathogen inactivation by ultraviolet C light in platelet concentrates. Transfusion 2018; 58:758–65
    1. Mohr H, Lambrecht B, Selz A: Photodynamic virus inactivation of blood components. Immunol Invest 1995; 24:73–85
    1. Seghatchian J, Walker WH, Reichenberg S: Updates on pathogen inactivation of plasma using Theraflex methylene blue system. Transfus Apher Sci 2008; 38:271–80
    1. Politis C, Kavallierou L, Hantziara S, et al: Haemovigilance data on the use of methylene blue virally inactivated fresh frozen plasma with the Theraflex MB‐Plasma System in comparison to quarantine plasma: 11 years' experience. Transfus Med 2014; 24:316–20
    1. Williamson LM, Cardigan R, Prowse CV: Methylene blue‐treated fresh‐frozen plasma: what is its contribution to blood safety? Transfusion 2003; 43:1322–9
    1. Faddy HM, Fryk JJ, Prow NA, et al: Inactivation of dengue, chikungunya, and Ross River viruses in platelet concentrates after treatment with ultraviolet C light. Transfusion 2016; 56:1548–55
    1. Fryk JJ, Marks DC, Hobson‐Peters J, et al: Reduction of Zika virus infectivity in platelet concentrates after treatment with ultraviolet C light and in plasma after treatment with methylene blue and visible light. Transfusion 2017; 57:2677–82
    1. Eickmann M, Gravemann U, Handke W, et al: Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively. Transfusion 2018; 58:2202–7
    1. Arnason NA, Johannson F, Landro R, et al: Pathogen inactivation with amotosalen plus UVA illumination minimally impacts microRNA expression in platelets during storage under standard blood banking conditions. Transfusion 2019; 59:3727–3735
    1. Castro E, Girones N, Guerrero N, et al: The effectiveness of UVC pathogen inactivation system on reducing the Trypansosoma cruzi and Leishmania infantum burden in platelets. Vox Sang 2008; 95:290
    1. Castro E, Gonzalez LM, Rubio JM, et al: The efficacy of the ultraviolet C pathogen inactivation system in the reduction of Babesia divergens in pooled buffy coat platelets. Transfusion 2014; 54:2207–16
    1. Gravemann U, Handke W, Lambrecht B, et al: Ultraviolet C light efficiently inactivates nonenveloped hepatitis A virus and feline calicivirus in platelet concentrates. Transfusion 2018; 58:2669–74
    1. Gravemann U, Handke W, Muller TH, et al: Bacterial inactivation of platelet concentrates with the THERAFLEX UV‐Platelets pathogen inactivation system. Transfusion 2019; 59:1324–32
    1. Seghatchian J, Struff WG, Reichenberg S: Main properties of the THERAFLEX MB‐plasma system for pathogen reduction. Transf Med Hemother 2011; 38:55–64
    1. Spearman C: The method of "right and wrong cases" ("constant stimuli") without Gauss's formulae. Br J Psychol 1908; 2:277–82
    1. Kaerber G: Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol 1931; 162:480–3
    1. Agafonov AP, Gus'kov AA, Ternovoi VA, et al: Primary characterization of SARS coronavirus strain Frankfurt 1. Dokl Biol Sci 2004; 394:58–60
    1. Olschlager S, Gabriel M, Schmidt‐Chanasit J, et al: Complete sequence and phylogenetic characterisation of Crimean‐Congo hemorrhagic fever virus from Afghanistan. J Clin Virol 2011; 50:90–2
    1. Wild TF: Henipaviruses: a new family of emerging Paramyxoviruses. Pathol Biol (Paris) 2009; 57:188–96
    1. Woolhouse ME, Haydon DT, Antia R: Emerging pathogens: the epidemiology and evolution of species jumps. Trends Ecol Evol 2005; 20:238–44
    1. de Wit E, van Doremalen N, Falzarano D, et al: SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 2016; 14:523–34
    1. Dunstan RA, Seed CR, Keller AJ: Emerging viral threats to the Australian blood supply. Aust N Z J Public Health 2008; 32:354–60
    1. Bente DA, Forrester NL, Watts DM, et al: Crimean‐Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity. Antiviral Res 2013; 100:159–89
    1. Conger NG, Paolino KM, Osborn EC, et al: Health care response to CCHF in US soldier and nosocomial transmission to health care providers, Germany, 2009. Emerg Infect Dis 2015; 21:23–31
    1. Sharma V, Kaushik S, Kumar R, et al: Emerging trends of Nipah virus: A review. Rev Med Virol 2019; 29:e2010
    1. Ang BSP, Lim TCC, Wang L: Nipah virus infection. J Clin Microbiol 2018. 56(6):e01875‐17
    1. Nikolay B, Salje H, Hossain MJ, et al: Transmission of nipah virus ‐ 14 years of investigations in Bangladesh. N Engl J Med 2019; 380:1804–14
    1. McCullough J, Alter HJ, Ness PM: Interpretation of pathogen load in relationship to infectivity and pathogen reduction efficacy. Transfusion 2019; 59:1132–46

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