| Title: |
Zanamivir and baloxavir combination to cure persistent influenza and coronavirus infections after hematopoietic stem cell transplant |
| Authors: |
Euzen, Victor; Xhaard, Aliénor; Berreira-Ibraim, Samar; Deville, Laure; Quentin, Aude; de Lima Prata, Pedro Hendrique; Gournay, Viviane; Prot, Matthieu; Rahou, Yannis; Barbet, Marion; Mercier-Delarue, Séverine; Peffault de la Tour, Régis; Simon-Loriere, Etienne; Legoff, Jérôme |
| Contributors: |
Laboratoire de Virologie CHU Saint-Louis; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Service Hématologie Transplantation Hôpital Saint Louis, AP-HP; Hopital Saint-Louis AP-HP (AP-HP); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Centre National de Référence des virus respiratoires (dont la grippe et le SARS-CoV2) Paris (CNR - laboratoire associé); Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Pharmacie Hôpital Saint-Louis, AP-HP; Hôpital Jean Jaurès Paris (GROUPE SOS Santé); Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses; The study was funded by Assitance Publique Hôpitaux de Paris (APHP). This study has also received funding from Institut Pasteur and Santé publique France (the French national public health agency). ESL laboratory is funded by the INCEPTION programme (Investissements d'Avenir grant ANR-16-CONV-0005), Laboratoire d'Excellence “Integrative Biology of Emerging Infectious Diseases” (grant n°ANR-10-LABX-62-IBEID), the NIH PICREID programme (Award Number U01AI151758), the HERA European program DURABLE (101102733).; ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016); ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); European Project: 101102733,EU4Health,DURABLE(2023) |
| Source: |
ISSN: 0924-8579. |
| Publisher Information: |
CCSD |
| Publication Year: |
2024 |
| Subject Terms: |
Neuraminidase inhibitor; Baloxavir-marboxil; Influenza; Transplantation; Drug-resistant; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; ObjectivesImmunocompromised patients may experience prolonged shedding of influenza virus potentially leading to severe infections. Alternatives to monotherapy with neuraminidase inhibitors should be evaluated to entirely suppress viral replication and prevent drug-resistant mutations.MethodsWe investigated the clinical and virological evolution in a case of persistent influenza A and human coronavirus OC43 (HCoV-OC43) coinfection in a hematopoietic stem cell transplant recipient after different therapeutic strategies.ResultsSuccessive oseltamivir and zanamivir monotherapies failed to control both infections, with positive results persisting for over 110 days each. This led to the emergence of highly resistant oseltamivir strains due to neuraminidase mutations (E119V and R292K) followed by a deletion (del245-248), while maintaining sensitivity to zanamivir. The intra-host viral diversity data showed that the treatments impacted viral diversity of influenza virus, but not of HCoV-OC43. Considering the patient's underlying condition and the impact of prolonged viral shedding on pulmonary function, eradicating the influenza virus was necessary. A 10-day regimen combining zanamivir and baloxavir-marboxil effectively controlled influenza virus replication and was associated with the clearance of HCoV-OC43, finally resulting in comprehensive respiratory recovery.ConclusionThese observations underscore the importance of further investigating combination treatments as the primary approach to achieve influenza eradication in immunocompromised patients. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39047913; info:eu-repo/grantAgreement//101102733/EU/Delivering a Unified Research Alliance of Biomedical and public health Laboratories against Epidemics/DURABLE; PUBMED: 39047913 |
| DOI: |
10.1016/j.ijantimicag.2024.107281 |
| Availability: |
https://hal.science/hal-04892150; https://hal.science/hal-04892150v1/document; https://hal.science/hal-04892150v1/file/1-s2.0-S0924857924001997-main.pdf; https://doi.org/10.1016/j.ijantimicag.2024.107281 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.A0B9D370 |
| Database: |
BASE |