Amotosalen and ultraviolet A light efficiently inactivate MERS-coronavirus in human platelet concentrates

A M Hashem, A M Hassan, A M Tolah, M A Alsaadi, Q Abunada, G A Damanhouri, S A El-Kafrawy, M Picard-Maureau, E I Azhar, S I Hindawi, A M Hashem, A M Hassan, A M Tolah, M A Alsaadi, Q Abunada, G A Damanhouri, S A El-Kafrawy, M Picard-Maureau, E I Azhar, S I Hindawi

Abstract

Objective: This study aimed to assess the efficacy of the INTERCEPT™ Blood System [amotosalen/ultraviolet A (UVA) light] to reduce the risk of Middle East respiratory syndrome-Coronavirus (MERS-CoV) transmission by human platelet concentrates.

Background: Since 2012, more than 2425 MERS-CoV human cases have been reported in 27 countries. The infection causes acute respiratory disease, which was responsible for 838 deaths in these countries, mainly in Saudi Arabia. Viral genomic RNA was detected in whole blood, serum and plasma of infected patients, raising concerns of the safety of blood supplies, especially in endemic areas.

Methods: Four apheresis platelet units in 100% plasma were inoculated with a clinical MERS-CoV isolate. Spiked units were then treated with amotosalen/UVA to inactivate MERS-CoV. Infectious and genomic viral titres were quantified by plaque assay and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). Inactivated samples were successively passaged thrice on Vero E6 cells to exclude the presence of residual replication-competent viral particles in inactivated platelets.

Results: Complete inactivation of MERS-CoV in spiked platelet units was achieved by treatment with Amotosalen/UVA light with a mean log reduction of 4·48 ± 0·3. Passaging of the inactivated samples in Vero E6 showed no viral replication even after nine days of incubation and three passages. Viral genomic RNA titration in inactivated samples showed titres comparable to those in pre-treatment samples.

Conclusion: Amotosalen and UVA light treatment of MERS-CoV-spiked platelet concentrates efficiently and completely inactivated MERS-CoV infectivity (>4 logs), suggesting that such treatment could minimise the risk of transfusion-related MERS-CoV transmission.

Keywords: MERS-CoV; UVA; amotosalen; pathogen inactivation; platelets.

Conflict of interest statement

QA and MPM are employees of the Cerus Corporation. The authors have no competing interests.

© 2019 British Blood Transfusion Society.

Figures

Figure 1
Figure 1
Experimental design. Schematic view of the experimental design.
Figure 2
Figure 2
Inhibition of MERS‐CoV in platelets by amotosalen and UVA treatment. Representative wells from the plaque assay are shown for all tested platelets units.
Figure 3
Figure 3
Complete inactivation of replicative MERS‐CoV by amotosalen and UVA treatment. Vero E6 cells were inoculated with DMEM only (Mock control), positive control, negative control, pre‐treatment sample or inactivated sample and were passaged for three consecutive passages. Both the positive control and the pre‐treatment sample caused extensive CPE by day 3 post‐inoculation in all three passages. Mock control, negative control and inactivated sample did not show any CPE in Vero E6 cells. Photographs (4×) are shown from one representative platelet unit on day 3 post‐inoculation in each passage.

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Source: PubMed

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