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

• Published in: International journal of antimicrobial agents 2024-09, Vol.64 (3), p.107281, Article 107281
• Main 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
• Format: Article
• Language: English
• Subjects: Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Baloxavir-marboxil; Coronavirus Infections - drug therapy; Coronavirus Infections - virology; Coronavirus OC43, Human - drug effects; Coronavirus OC43, Human - genetics; Dibenzothiepins - therapeutic use; Drug Resistance, Viral - genetics; Drug Therapy, Combination; Drug-resistant; Female; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Immunocompromised Host; Influenza; Influenza A virus - drug effects; Influenza A virus - genetics; Influenza, Human - drug therapy; Influenza, Human - virology; Male; Middle Aged; Morpholines - therapeutic use; Neuraminidase inhibitor; Pyridones - therapeutic use; Transplantation; Triazines - pharmacology; Triazines - therapeutic use; Virus Replication - drug effects; Virus Shedding - drug effects; Zanamivir - pharmacology; Zanamivir - therapeutic use
• ISSN: 0924-8579; 1872-7913; 1872-7913
• DOI: 10.1016/j.ijantimicag.2024.107281

•Transplant patients experience prolonged respiratory virus infections.•Monotherapy with neuraminidase inhibitors failed to cure influenza virus infection.•Neuraminidase inhibitor monotherapy led to the emergence of drug-resistant strains.•The combination of zanamivir and baloxavir marboxil suppressed persistent Influenza infection.•The clearance of Influenza and HCoV-OC43 resulted in full respiratory recovery. Immunocompromised 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. 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. Successive 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. These observations underscore the importance of further investigating combination treatments as the primary approach to achieve influenza eradication in immunocompromised patients.