Pathogen reduction with methylene blue does not have an impact on the clinical effectiveness of COVID‐19 convalescent plasma

Author:

Romera Martínez Irene12ORCID,Bueno Cabrera José Luis12,Domingo‐Morera José María3,López Aguilar Juan Carlos4,Villegas Da Ros Carolina5,García Erce José Antonio678,Sáez Serrano Isabel9,Flores Ballester Elena10,Maglio Laura Analía11,Arbona Castaño Cristina12,Sola Lapeña Carlos13,Guerra Domínguez Luisa14,Berberana Fernández Margarita15,Madrigal Sánchez María Elena16,Rubio Batllés Martín17,Pérez‐Olmeda Mayte1819,Ramos‐Martínez Antonio20,Velasco‐Iglesias Ana21,Avendaño‐Solá Cristina2223,Duarte Rafael F.12

Affiliation:

1. Department of Hematology Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain

2. Instituto de Investigación Sanitaria Hospital Puerta de Hierro‐Segovia de Arana Madrid Spain

3. Banco de Sangre y Tejidos de Aragón Zaragoza Spain

4. Centro de Transfusión de las Fuerzas Armadas Madrid Spain

5. Department of Hematology Hospital Universitario 12 de Octubre Madrid Spain

6. Banco de Sangre y Tejidos de Navarra Servicio Navarro de Salud, Osasunbidea Pamplona Spain

7. Grupo Español de Rehabilitación Multimodal (GERM) Instituto Aragonés de Ciencias de la Salud Zaragoza Spain

8. PBM Group Hospital La Paz Institute for Health Research (IdiPAZ) Madrid Spain

9. Department of Hematology Hospital Universitario Clínico San Carlos Madrid Spain

10. Department of Hematology Hospital Universitario Príncipe de Asturias Madrid Spain

11. Banco de Sangre y Tejidos de Manresa Barcelona Spain

12. Centro de Transfusión de la Comunidad Valenciana Valencia Spain

13. Centro de Transfusión‐Banco de Sangre de La Rioja Logroño Spain

14. Department of Hematology Hospital Universitario de Gran Canaria Doctor Negrín Las Palmas Spain

15. Department of Hematology Hospital Universitario Severo Ochoa Madrid Spain

16. Centro de Transfusión de Ciudad Real Hospital General Universitario de Ciudad Real Ciudad Real Spain

17. Centro Transfusión de Albacete y Cuenca Albacete Spain

18. Laboratorio de Serología Centro Nacional de Microbiología, Instituto de Salud Carlos III Madrid Spain

19. Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) Instituto de Salud Carlos III (ISCIII) Madrid Spain

20. Infectious Diseases Unit, Department of Internal Medicine Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain

21. Spanish Clinical Research Network (ISCIII) IIS ‐Hospital Puerta de Hierro‐Segovia de Arana Madrid Spain

22. Clinical Pharmacology Department Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain

23. Instituto de Investigación Sanitaria Hospital Puerta de Hierro‐Segovia de Arana, SCReN Clinical Trials Platform Madrid Spain

Abstract

AbstractBackground and ObjectivesThere is a concern about a possible deleterious effect of pathogen reduction (PR) with methylene blue (MB) on the function of immunoglobulins of COVID‐19 convalescent plasma (CCP). We have evaluated whether MB‐treated CCP is associated with a poorer clinical response compared to other inactivation systems at the ConPlas‐19 clinical trial.Materials and MethodsThis was an ad hoc sub‐study of the ConPlas‐19 clinical trial comparing the proportion of patients transfused with MB‐treated CCP who had a worsening of respiration versus those treated with amotosalen (AM) or riboflavin (RB).ResultsOne‐hundred and seventy‐five inpatients with SARS‐CoV‐2 pneumonia were transfused with a single CCP unit. The inactivation system of the CCP units transfused was MB in 90 patients (51.4%), RB in 60 (34.3%) and AM in 25 (14.3%). Five out of 90 patients (5.6%) transfused with MB‐treated CCP had worsening respiration compared to 9 out of 85 patients (10.6%) treated with alternative PR methods (p = 0.220). Of note, MB showed a trend towards a lower rate of respiratory progressions at 28 days (risk ratio, 0.52; 95% confidence interval, 0.18–1.50).ConclusionOur data suggest that MB‐treated CCP does not provide a worse clinical outcome compared to the other PR methods for the treatment of COVID‐19.

Funder

Instituto de Salud Carlos III

Publisher

Wiley

Subject

Hematology,General Medicine

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