Background: Highly pathogenic avian influenza A (H5N6) virus poses a continuous threat to human health since 2014. Although neuraminidase inhibitors (NAIs) are prescribed in most patients infected with the H5N6 virus, the fatality remains high, indicating the need for an improved treatment regimen. Sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), has been reported to reduce viral replication and improve clinical outcomes in severe H1N1 infections when combined with oseltamivir. Here, we report the first case of severe H5N6 pneumonia successfully treated by sirolimus and NAIs.

Case description: A 22-year-old man developed high fever and chills on September 24, 2018 (Day-0) and was hospitalized on Day-3. Influenza A (H5N6) was identified on Day-6 from a throat swab specimen. Despite the administration of NAIs and other supportive measures, the patient´s clinical conditions and lung images showed continued deterioration, accompanied by persistently high viral titers. Consequently, sirolimus administration (rapamycin; 2 mg per day for 14 days) was started on Day-12. His PaO2/FiO2 values and Sequential Organ Failure Assessment (SOFA) score gradually improved, and imaging outcomes revealed the resolution of bilateral lung infiltrations. The viral titer gradually decreased and turned negative on Day-25. Sirolimus and NAIs were stopped on the same day. The patient was discharged on Day-65. Based on observations from a 2-year follow-up, the patient was found to be in a good condition without complications.

Conclusions: In conclusion, sirolimus might be a novel and practical therapeutic approach to severe H5N6-associated pneumonia in humans.