Pathogen Reduction of SARS-CoV-2 Virus in Plasma and Whole Blood using Riboflavin and UV Light
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Abstract
BACKGROUND
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently been identified as the causative agent for Coronavirus Disease 2019 (COVID-19). The ability of this agent to be transmitted by blood transfusion has not been documented, although viral RNA has been detected in serum. Exposure to treatment with riboflavin and ultraviolet light (R + UV) reduces blood-borne pathogens while maintaining blood product quality. Here, we report on the efficacy of R + UV in reducing SARS-CoV-2 infectivity when tested in human plasma and whole blood products.
STUDY DESIGN AND METHODS
SARS-CoV-2 (isolate USA-WA1/2020) was used to inoculate plasma and whole blood units that then underwent treatment with riboflavin and UV light (Mirasol Pathogen Reduction Technology System, Terumo BCT, Lakewood, CO). The infectious titers of SARS-CoV-2 in the samples before and after R + UV treatment were determined by plaque assay on Vero cells. Each plasma pool (n=9) underwent R + UV treatment performed in triplicate using individual units of plasma and then repeated using individual whole blood donations (n=3).
RESULTS
Riboflavin and UV light reduced the infectious titer of SARS-CoV-2 below the limit of detection for plasma products at 60-100% of the recommended energy dose. At the UV light dose recommended by the manufacturer, the mean log reductions in the viral titers were ≥ 4.79 ± 0.15 Logs in plasma and 3.30 ± 0.26 in whole blood units.
CONCLUSION
Riboflavin and UV light effectively reduced the titer of SARS-CoV-2 to the limit of detection in human plasma and by 3.30 ± 0.26 on average in whole blood. Two clades of SARS-CoV-2 have been described and questions remain about whether exposure to one strain confers strong immunity to the other. Pathogen-reduced blood products may be a safer option for critically ill patients with COVID-19, particularly those in high-risk categories.
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SciScore for 10.1101/2020.05.03.074971: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Plaque assays were performed using Vero cells at confluency in 6-well cell culture plates. Verosuggested: NoneSoftware and Algorithms Sentences Resources Riboflavin solution (35 mL, 500 μmol/L) was added to each product, followed by inoculation with 5 mL SARS-CoV-2 virus, and the bags were placed into the Illuminator (Mirasol PRT System, Terumo BCT, Lakewood, CO) for treatment with UV light. Illuminatorsuggested: (Illuminator, RRID:SCR_0010…SciScore for 10.1101/2020.05.03.074971: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Plaque assays were performed using Vero cells at confluency in 6-well cell culture plates. Verosuggested: NoneSoftware and Algorithms Sentences Resources Riboflavin solution (35 mL, 500 μmol/L) was added to each product, followed by inoculation with 5 mL SARS-CoV-2 virus, and the bags were placed into the Illuminator (Mirasol PRT System, Terumo BCT, Lakewood, CO) for treatment with UV light. Illuminatorsuggested: (Illuminator, RRID:SCR_001019)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has limitations. Other blood components such as platelets and red blood cells were not assessed. Plasma and whole blood from infected patients were not assessed for infectivity. The capacity of transfused blood products from an animal infected with SARS-CoV-2 to cause disease was not assessed but is the focus of ongoing studies in our labs. The limit of detection was reached in the plasma experiments thus the full range of pathogen inactivation was not measured but is greater than 4.79 ± 0.15 logs at the UV dose recommended by the manufacturer. SARS-CoV-2 has demonstrated frequent mutations since it was first recognized in December of 2019, evolving into two different strains (designated L and S), suggesting a possible propensity to develop subtypes that could result in seasonal variability and lack of immunity to the new strains for those exposed to the previous strains (16). To date, the differences in the two strains appear to be related to infectivity and the impact on conferred immunity is not clear. In the setting of this rapidly expanding pandemic, a significant number of severely ill patients, and unclear transmissibility in blood, experts are advising caution. Even though a mere month has passed since the article by Drs. Dodd and Stramer were published, it is becoming clear that deferment is becoming increasing untenable as a strategy to address the risk (6). Pathogen reduction may be the only viable solution to protect the blood supply during this crisis.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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