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 ca...

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Main Authors: Bálint Gergely Szabó, Anna Nagy, Orsolya Nagy, Anita Koroknai, Nikolett Csonka, Dorina Korózs, Krisztina Jeszenszky, Apor Hardi, Nóra Deézsi-Magyar, János Sztikler, Zoltán Bódi, Dániel Cadar, Gábor Endre Tóth, Liliána Veres, Erzsébet Barcsay, Mária Takács, János Sinkó
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Language:English
Published: BMC 2025-07-01
Series:Virology Journal
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Online Access:https://doi.org/10.1186/s12985-025-02890-9
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author Bálint Gergely Szabó
Anna Nagy
Orsolya Nagy
Anita Koroknai
Nikolett Csonka
Dorina Korózs
Krisztina Jeszenszky
Apor Hardi
Nóra Deézsi-Magyar
János Sztikler
Zoltán Bódi
Dániel Cadar
Gábor Endre Tóth
Liliána Veres
Erzsébet Barcsay
Mária Takács
János Sinkó
author_facet Bálint Gergely Szabó
Anna Nagy
Orsolya Nagy
Anita Koroknai
Nikolett Csonka
Dorina Korózs
Krisztina Jeszenszky
Apor Hardi
Nóra Deézsi-Magyar
János Sztikler
Zoltán Bódi
Dániel Cadar
Gábor Endre Tóth
Liliána Veres
Erzsébet Barcsay
Mária Takács
János Sinkó
author_sort Bálint Gergely Szabó
collection DOAJ
description 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.
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spelling doaj-art-b32cbd00790e4897bbb080a88005439f2025-08-20T03:45:45ZengBMCVirology Journal1743-422X2025-07-0122111510.1186/s12985-025-02890-9First documented case of a fatal autochthonous Usutu virus infection in an immunocompromised patient in Hungary: a clinical-virological report and implications from the literatureBálint Gergely Szabó0Anna Nagy1Orsolya Nagy2Anita Koroknai3Nikolett Csonka4Dorina Korózs5Krisztina Jeszenszky6Apor Hardi7Nóra Deézsi-Magyar8János Sztikler9Zoltán Bódi10Dániel Cadar11Gábor Endre Tóth12Liliána Veres13Erzsébet Barcsay14Mária Takács15János Sinkó16Departmental Group of Infectious Diseases, Department of Internal Medicine and Haematology, Semmelweis UniversityNational Reference Laboratory for Viral Zoonoses, National Center for Public Health and PharmacyNational Reference Laboratory for Viral Zoonoses, National Center for Public Health and PharmacyNational Reference Laboratory for Viral Zoonoses, National Center for Public Health and PharmacyNational Reference Laboratory for Viral Zoonoses, National Center for Public Health and PharmacyDoctoral College, Semmelweis UniversityDoctoral College, Semmelweis UniversitySouth Pest Central Hospital, National Institute of Hematology and Infectious DiseasesNational Biosafety Laboratory, National Center for Public Health and PharmacyDepartment of Bacteriological, Mycological and Parasitological Reference Laboratory, National Center for Public Health and PharmacyDepartment of Bacteriological, Mycological and Parasitological Reference Laboratory, National Center for Public Health and PharmacyBernhard Nocht Institute for Tropical MedicineBernhard Nocht Institute for Tropical MedicineFaculty of Medicine, Semmelweis UniversityDepartment of Virology, National Center for Public Health and PharmacyInstitute of Medical Microbiology, Semmelweis UniversitySouth Pest Central Hospital, National Institute of Hematology and Infectious DiseasesAbstract 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.https://doi.org/10.1186/s12985-025-02890-9Usutu virusUSUVOrthoflavivirusZoonotic virusImmunocompromised host
spellingShingle Bálint Gergely Szabó
Anna Nagy
Orsolya Nagy
Anita Koroknai
Nikolett Csonka
Dorina Korózs
Krisztina Jeszenszky
Apor Hardi
Nóra Deézsi-Magyar
János Sztikler
Zoltán Bódi
Dániel Cadar
Gábor Endre Tóth
Liliána Veres
Erzsébet Barcsay
Mária Takács
János Sinkó
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
Virology Journal
Usutu virus
USUV
Orthoflavivirus
Zoonotic virus
Immunocompromised host
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Usutu virus
USUV
Orthoflavivirus
Zoonotic virus
Immunocompromised host
url https://doi.org/10.1186/s12985-025-02890-9
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