J Fungi (Basel) . Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis

[tetano]

J Fungi (Basel)


. 2021 Dec 21;8(1):1.
doi: 10.3390/jof8010001.
Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis


Laura Seldeslachts ¹ , Cato Jacobs ² , Birger Tielemans ¹ , Eliane Vanhoffelen ¹ , Lauren Van der Sloten ² , Stephanie Humblet-Baron ³ , Lieve Naesens ⁴ , Katrien Lagrou ⁵ , Erik Verbeken ⁶ , Joost Wauters ² , Greetje Vande Velde ¹



Affiliations

• PMID: 35049941
• DOI: 10.3390/jof8010001

Abstract

Influenza-associated pulmonary aspergillosis (IAPA) is a global recognized superinfection in critically ill influenza patients. Baloxavir marboxil, a cap-dependent endonuclease inhibitor, is a newly approved anti-influenza therapeutic. Although the benefits as a treatment for influenza are clear, its efficacy against an influenza-A. fumigatus co-infection has yet to be determined. We investigated the therapeutic effect of baloxavir marboxil in a murine model for IAPA. Immunocompetent mice received intranasal instillation of influenza A followed by orotracheal inoculation with Aspergillus fumigatus 4 days later. Administration of baloxavir marboxil or sham was started at day 0, day 2 or day 4. Mice were monitored daily for overall health status, lung pathology with micro-computed tomography (µCT) and fungal burden with bioluminescence imaging (BLI). In vivo imaging was supplemented with virological, mycological and biochemical endpoint investigations. We observed an improved body weight, survival and viral clearance in baloxavir marboxil treated mice. µCT showed less pulmonary lesions and bronchial dilation after influenza and after Aspergillus co-infection in a treatment-dependent pattern. Furthermore, baloxavir marboxil was associated with effective inhibition of fungal invasion. Hence, our results provide evidence that baloxavir marboxil mitigates severe influenza thereby decreasing the susceptibility to a lethal invasive Aspergillus superinfection.

Keywords: Aspergillus fumigatus; baloxavir marboxil; influenza; influenza-associated pulmonary aspergillosis (IAPA); multimodal preclinical imaging-supported mouse model.