Pathogen reduction of monkeypox virus in plasma and whole blood using riboflavin and UV light

Abstract

Background Monkeypox virus has recently emerged from endemic foci in Africa and, since October 20, 2022, more than 73,000 human infections have been reported by the CDC from over 100 countries that historically have not reported monkeypox cases. The detection of virus in skin lesions, blood, semen, and saliva of infected patients with monkeypox infections raises the potential for disease transmission via routes that have not been previously documented, including by blood and plasma transfusions. Methods for protecting the blood supply against the threats of newly emerging disease agents exist and include Pathogen Reduction Technologies (PRT) which utilize photochemical treatment processes to inactivate pathogens in blood while preserving the integrity of plasma and cellular components. Such methods have been employed broadly for over 15 years, but effectiveness of these methods under routine use conditions against monkeypox virus has not been reported. Study design and methods Monkeypox virus (strain USA_2003) was used to inoculate plasma and whole blood units that were then treated with riboflavin and UV light (Mirasol Pathogen Reduction Technology System, Terumo BCT, Lakewood, CO). The infectious titers of monkeypox virus in the samples before and after riboflavin + UV treatment were determined by plaque assay on Vero cells. Results The levels of spiked virus present in whole blood and plasma samples exceeded 103 infectious particles per dose, corresponding to greater than 105 DNA copies per mL. Treatment of whole blood and plasma units under standard operating procedures for the Mirasol PRT System resulted in complete inactivation of infectivity to the limits of detection. This is equivalent to a reduction of ≥ 2.86 +/- 0.73 log10 pfu/mL of infectivity in whole blood and ≥ 3.47 +/-0.19 log10 pfu/mL of infectivity in plasma under standard operating conditions for those products. Conclusion Based on this data and corresponding studies on infectivity in patients with monkeypox infections, use of Mirasol PRT would be expected to significantly reduce the risk of transfusion transmission of monkeypox.

Virological characterization of the 2022 outbreak‐causing monkeypox virus using human keratinocytes and colon organoids

“…Virus infectious titers were determined by plaque assay 31 . One day before infection, VeroE6 cells (0.2 million cells) were seeded into a 12‐well plate and infected with MPXV.…”

“…Virus infectious titers were determined by plaque assay. 31 One day before infection, VeroE6 cells (0.2 million cells) were seeded into a 12-well plate and infected with MPXV. Before infection, the culture medium was changed to DMEM (low glucose) containing 2% FBS, and 1% penicillin−streptomycin.…”

Emerging Pathogen Threats in Transfusion Medicine: Improving Safety and Confidence with Pathogen Reduction Technologies

“…To evaluate the effectiveness of the Mirasol PRT System against the mpox virus that emerged in 2022, plasma and whole blood products (n = three of each) were inoculated with the mpox virus (USA_2003), with pre-treatment titers of 3.50 and 3.08 log10 pfu/mL, respectively [ 127 ]. These pre-treatment viral titers were clinically relevant based on the amount of the virus detected in the patients infected with the mpox virus.…”

Transfusion-Transmitted Disorders 2023 with Special Attention to Bone Marrow Transplant Patients

“…While transfusion transmission of monkeypox virus (MPXV) has not been reported, the potential of transfusion transmission seems to be supported by evidence [ 92 , 93 , 94 ]. However, it is currently not recommended for blood banks to ask donors specific questions about possible exposure to the monkeypox virus or to use diagnostic tests to screen patients and blood products for monkeypox virus [ 95 ].…”

“…New-generation inactivation methods became standard elements of European preparative transfusiology standards, in which chemical intervention combined with ultraviolet light became a widely applied method in many European countries [ 1 , 4 , 22 , 41 , 42 , 94 , 96 , 102 ].…”