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

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.