Inactivation of Middle East respiratory syndrome‐coronavirus in human plasma using amotosalen and ultraviolet A light

Abstract

BACKGROUND: Middle East respiratory syndromecoronavirus (MERS-CoV) is a novel zoonotic pathogen. Although the potential for MERS-CoV transmission through blood transfusion is not clear, MERS-CoV was recognized as a pathogen of concern for the safety of the blood supply especially after its detection in whole blood, serum, and plasma of infected individuals. Here we investigated the efficacy of amotosalen and ultraviolet A light (UVA) to inactivate MERS-CoV in fresh-frozen plasma (FFP). STUDY DESIGN AND METHODS: Pooled FFP unitswere spiked with a recent clinical MERS-CoV isolate. Infectious and genomic viral titers were determined in plasma before and after inactivation with amotosalen/ UVA treatment by plaque assay and reverse transcription-quantitative polymerase chain reaction, respectively. In addition, residual replicating or live virus after inactivation was examined by passaging in the permissive Vero E6 cells. RESULTS:The mean MERS-CoV infectious titer in pretreatment samples was 4.67 6 0.25 log plaqueforming units (pfu)/mL, which was reduced to undetectable levels after inactivation with amotosalen/ UVA demonstrating a mean log reduction of more than 4.67 6 0.25 pfu/mL. Furthermore, inoculation of inactivated plasma on Vero E6 cells did not result in any cytopathic effect (CPE) even after 7 days of incubation and three consecutive passages, nor the detection of MERS RNA compared to pretreatment samples which showed complete CPE within 2 to 3 days postinoculation and log viral RNA titer ranging from 9.48 to 10.22 copies/ mL in all three passages. CONCLUSION:Our data show that amotosalen/UVA treatment is a potent and effective way to inactivate MERS-CoV infectious particles in FFP to undetectable levels and to minimize the risk of any possible transfusion-related MERS-CoV transmission.T ransfusion of blood components saves millions of lives by controlling bleeding due to accidents, surgeries, or other disease complications. However, transmission of pathogens is one of the biggest risks of transfusion of labile blood components. Therefore, a key mission of blood transfusion services is to provide safe blood and blood products. Screening of blood products has reduced the spread of known blood-borne pathogens such as hepatitis B and C viruses (HBV and HCV), human immunodeficiency virus (HIV), and human T-lymphotropic virus (HTLV). unknown pathogens pose a threat to the blood supply with regional differences that is difficult to address. The number of pathogens screened in blood banks is limited by the number of blood screening assays that are commercially available. Therefore, pathogen inactivation offers an appealing alternative to blood screening (serology or nucleic acid testing [NAT]) because of its proactive nature and the broad spectrum of protection it offers without a priori characterization of unknown pathogens. Indeed, pathogen inactivation technologies have been developed to provide safe blood products while reducing the need for the implementation of additional screening assays. 3The Middle East r...

Coronavirus Disease 2019: Coronaviruses and Blood Safety

“…The infectious titer of virus did not show any significant reduction after 25 cycles of thawing and freezing [44]. After the outbreak of SARS and MERS, a few studies investigated pathogen inactivation/reduction technologies (PRTs) based on in-house or commercial methods with the aim to decrease or completely eradicate the potential risk of transmission of coronaviruses via blood products or blood derivatives [45][46][47][48][49][50][51][52][53][54]. These studies are summarized in Table 1.…”

“…Illumination with different wavelengths also influenced activities of SARS and MERS virus in blood. Ultraviolet (UV)-A [46,47,51]and UV-B light [54] in the presence of amotosalen or riboflavin could inactivate the pathogens' nucleic acids, whereas a third PRT method uses UV-C light only [45,48]. These commercial systems could reduce the activities of SARS and MERS virus in plasma or platelet concentrates to different degrees.…”

Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets

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A Systematic Review of therapeutic agents for the treatment of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

“…An Estrogen receptor I antagonist, Toremifene citrate, had activity against MERS-CoV [42]. In addition, MERS-CoV is inactivated by amotosalen and ultraviolet light in fresh frozen plasma [49].…”