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Clinical and genomic characterisation of a fatal Puumala orthohantavirus case with low levels of neutralising antibodies
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.ORCID iD: 0000-0002-8753-830x
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2022 (English)In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 54, no 10, p. 766-772Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Orthohantaviruses are rodent-borne emerging viruses that cause haemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in America. Transmission between humans have been reported and the case-fatality rate ranges from 0.4% to 40% depending on virus strain. There is no specific and efficient treatment for patients with severe HFRS. Here, we characterised a fatal case of HFRS and sequenced the causing Puumala orthohantavirus (PUUV).

METHODS: PUUV RNA and virus specific neutralising antibodies were quantified in plasma samples from the fatal case and other patients with non-fatal PUUV infection. To investigate if the causing PUUV strain was different from previously known strains, Sanger sequencing was performed directly from the patient's plasma. Biopsies obtained from autopsy were stained for immunohistochemistry.

RESULTS: The patient had approximately tenfold lower levels of PUUV neutralising antibodies and twice higher viral load than was normally seen for patients with less severe PUUV infection. We could demonstrate unique mutations in the S and M segments of the virus that could have had an impact on the severity of infection. Due to the severe course of infection, the patient was treated with the bradykinin receptor inhibitor icatibant to reduce bradykinin-mediated vessel permeability and maintain vascular circulation.

CONCLUSIONS: Our data suggest that bradykinin receptor inhibitor may not be highly efficient to treat patients that are at an advanced stage of HFRS. Low neutralising antibodies and high viral load at admission to the hospital were associated with the fatal outcome and may be useful for future predictions of disease outcome.

Place, publisher, year, edition, pages
2022. Vol. 54, no 10, p. 766-772
Keywords [en]
Icatibant, Puumala orthohantavirus, neutralising antibodies, orthohantavirus, viral load, virus sequence
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-201272DOI: 10.1080/23744235.2022.2076904ISI: 000812658600001PubMedID: 35713235Scopus ID: 2-s2.0-85132173959OAI: oai:DiVA.org:umu-201272DiVA, id: diva2:1713391
Funder
Region Västerbotten, RV-938855Region Västerbotten, RV-734361Swedish Heart Lung Foundation, 2017-0334Swedish Research Council, 2020-06235Lars Hierta Memorial Foundation, FO2018- 0470Available from: 2022-11-25 Created: 2022-11-25 Last updated: 2022-11-28Bibliographically approved

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Tuiskunen-Bäck, AnneRasmuson, JohanThunberg, ThereseRankin, GregoryWigren Byström, JuliaAndersson, CharlottaForsell, MattiasAhlm, Clas

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Tuiskunen-Bäck, AnneRasmuson, JohanThunberg, ThereseRankin, GregoryWigren Byström, JuliaAndersson, CharlottaSjödin, AndreasForsell, MattiasAhlm, Clas
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