Zanamivir and baloxavir combination to cure persistent influenza and coronavirus infections after hematopoietic stem cell transplant

International Journal of Antimicrobial Agents

Victor Euzen ∗, Aliénor Xhaard ∗, Samar Berreira-Ibraim ∗, Laure Deville, Aude Quentin, Pedro Hendrique De Lima Prata, Viviane Gournay, Matthieu Prot, Yannis Rahou, Marion Barbet, Séverine Mercier-Delarue, Régis Peffault De La Tour, Etienne Simon-Loriere $, Jérôme Legoff

Abstract

Objectives: Immunocompromised patients may experience prolonged shedding of influenza virus poten- tially leading to severe infections. Alternatives to monotherapy with neuraminidase inhibitors should be evaluated to entirely suppress viral replication and prevent drug-resistant mutations.

Methods: We 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.

Results: Successive oseltamivir and zanamivir monotherapies failed to control both infections, with pos- itive 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 im- pacted viral diversity of influenza virus, but not of HCoV-OC43. Considering the patient’s underlying con- dition 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 in- fluenza virus replication and was associated with the clearance of HCoV-OC43, finally resulting in com- prehensive respiratory recovery.

Conclusion: These observations underscore the importance of further investigating combination treat- ments as the primary approach to achieve influenza eradication in immunocompromised patients.

More information at DOI: https://doi.org/10.1016/j.ijantimicag.2024.107281