First documented case of a fatal autochthonous Usutu virus infection in an immunocompromised patient in Hungary: a clinical-virological report and implications from the literature

Abstract

Abstract Background Usutu virus (USUV) is a mosquito-borne neurotropic orthoflavivirus, endemic to Europe. Although incidental human infections have been recognized, comprehensive descriptions remain scarce. Herein, we report the clinical-virological analysis of the first documented autochthonous case of fatal USUV infection in a severely immunocompromised adult from Hungary. Clinical presentation A 61-year-old female with relapsed acute myelomonocytic leukemia developed progressive neurological symptoms, accompanied by high-grade fever, during post-chemotherapy aplasia. Initial cranial MRI revealed symmetric thalamic and brainstem abnormalities, while cerebrospinal fluid analysis showed mildly elevated protein levels. Despite empirical antimicrobial therapy, her status deteriorated with new-onset dysarthria and somnolence by day + 29 post-chemotherapy, requiring admission to the intensive care unit. Subsequent EEG demonstrated diffuse background slowing, and follow-up MRI confirmed further progression of the lesions. Despite supportive care and extensive microbiological testing, the patient died on day + 37 post-chemotherapy. Virological investigation USUV RNA was detected in CSF, blood, urine, and post-mortem tissues by RT-qPCR, using validated in-house protocols. Virus isolation was successfully achieved via intracranial inoculation of newborn mice and subsequent culture in Vero E6 cell cultures. Whole-genome sequencing and phylogenetic analysis confirmed infection with the USUV Europe 2 lineage, closely related to other Hungarian and Italian strains. No other pathogens from the central nervous system were identified. Conclusions We highlight the challenges of USUV infection in immunocompromised patients. The phylogenetic link between European strains shows the regional emergence of high-risk viral lineages. Surveillance, donor screening, and research into antiviral therapies are needed to mitigate the impact of this emerging arbovirus.

Keywords

• Usutu virus
• USUV
• Orthoflavivirus
• Zoonotic virus
• Immunocompromised host