Inactivation of <scp>M</scp>iddle <scp>E</scp>ast respiratory syndrome coronavirus (<scp>MERS‐C</scp>o<scp>V</scp>) in plasma products using a riboflavin‐based and ultraviolet light‐based photochemical treatment

Keil, Shawn D.; Bowen, Richard A.; Marschner, Susanne

doi:10.1111/trf.13860

Cited by 130 publications

(123 citation statements)

References 17 publications

(27 reference statements)

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“…A recent study investigated the inactivation of MERS-CoV in plasma using riboflavin and UV light. 47 The study showed a reduction of at least 4.07 and at least 4.42 log in viral titers for pooled and individual donor plasma, respectively. However, passaging experiments after pathogen reduction were not conducted, so complete inactivation of all infectious particles cannot be taken for granted.…”

Section: Discussionmentioning

confidence: 83%

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

et al. 2017

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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...

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Section: Discussionmentioning

confidence: 83%

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

et al. 2017

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“…It is documented that VB2 significantly improves serum and the histological parameters of hepatocellular damage and neutrophil infiltration following liver ischemia in mice [17]. Recently, many studies have also demonstrated that irradiated riboflavin protects the cisplatin-induced oxidative stress-mediated hepatotoxicity and nephrotoxicity in rodent based studies [47][48][49][50]. Furthermore, VB2 and UV light together were able to reduce the titer of MERS-CoV in human plasma products to a non-detecting level suggesting that the combination may lower the risk of transfusion transmission of MERS-CoV [51].…”

Section: Discussionmentioning

confidence: 98%

Potential effects of the combination of nicotinamide, vitamin B2 and vitamin C on oxidative-mediated hepatotoxicity induced by thioacetamide

et al. 2018

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BackgroundThe liver disease is one of the most important traditional public health problems in Egypt. Oxidative stress is attributed to such pathological condition that further contributes to the initiation and progression of liver injury. In the present study, we have investigated if the strong antioxidant power of Nicotinamide (NA), Vitamin B2 (VB2), and Vitamin C (VC) can ameliorate TAA-induced oxidative stress-mediated liver injury in the rats.MethodsThirty-six albino rats were divided into six groups: Control group; TAA group (IP injection with TAA at a dosage of 200 mg/Kg three times a week for two months); TAA + NA group (rats administered with NA at a dosage of 200 mg/kg daily besides TAA as in the control); TAA + VB2 group (rats administered with vitamin B2 at a dosage of 30 mg/kg daily besides injection with TAA); TAA + VC group (rats administered with vitamin C at a dosage of 200 mg/kg daily along with injection of TAA). TAA + NA + VB + VC group (rats administered the with the three vitamins daily in TAA pre-injected at the respective doses described above).ResultsTreatment of rats with TAA led to a significant elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total bilirubin, cholesterol, triglycerides, low-density lipoprotein (LDL) and tumor necrosis factor-alpha (TNF-α) in the serum samples. Moreover, malondialdehyde (MDA), hydroxyproline and nitic oxide (NO) were also significantly increased in the TAA-treated rats, while reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were significantly compromised in the hepatic samples. Rats administered with NA, VB2, and VC as individually or in combination ameliorated the deleterious effects of TAA that was confirmed by histopathology. However, the combination of the three vitamins was found more effective as compared to each of the vitamins.ConclusionOur work demonstrates that NA, VB2, and VC cross-talk with each other that act as a more potent biochemical chain of antioxidant defense against TAA-induced toxicities in vivo.

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“…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.…”

Section: Inactivation Of Coronavirus In Blood Productsmentioning

confidence: 99%

“…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.…”

Section: Inactivation Of Coronavirus In Blood Productsmentioning

confidence: 99%

Coronavirus Disease 2019: Coronaviruses and Blood Safety

Chang

Yan

Wang

2020

Transfusion Medicine Reviews

591

602

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Inactivation of Middle East respiratory syndrome coronavirus (MERS‐CoV) in plasma products using a riboflavin‐based and ultraviolet light‐based photochemical treatment

Abstract: Riboflavin and UV light effectively reduced the titer of MERS-CoV in human plasma products to below the limit of detection, suggesting that the treatment process may reduce the risk of transfusion transmission of MERS-CoV.

Cited by 130 publications

References 17 publications

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

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

Potential effects of the combination of nicotinamide, vitamin B2 and vitamin C on oxidative-mediated hepatotoxicity induced by thioacetamide

Coronavirus Disease 2019: Coronaviruses and Blood Safety

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