Umeå University's logo

umu.sePublications
Change search
Link to record
Permanent link

Direct link
Wigren, Julia
Alternative names
Publications (10 of 16) Show all publications
Waltraud, S., Schmuckenschlager, A., Thunberg, T., Wigren, J., Fors Connolly, A.-M., Assinger, A., . . . Forsell, M. N. E. (2024). Direct and indirect effects of Puumala hantavirus on platelet function. Thrombosis Research, 233, 41-54
Open this publication in new window or tab >>Direct and indirect effects of Puumala hantavirus on platelet function
Show others...
2024 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 233, p. 41-54Article in journal (Refereed) Published
Abstract [en]

Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation. Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration. Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.

Keywords
Hemorrhagic fever with renal syndrome, Immunothrombosis, Infection, Platelet dysfunction, Puumala hantavirus, Thrombocytopenia
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-217532 (URN)10.1016/j.thromres.2023.11.017 (DOI)2-s2.0-85177814613 (Scopus ID)
Funder
Region Västerbotten, RV-967545Region Västerbotten, RV-734361Umeå UniversitySwedish Heart Lung Foundation, 20170334Swedish Research Council, 2020-06235The Kempe Foundations, SMK-1560
Available from: 2023-12-14 Created: 2023-12-14 Last updated: 2023-12-14Bibliographically approved
Rosenbaum, W., Bovinder Ylitalo, E., Castel, G., Sjödin, A., Larsson, P., Wigren Byström, J., . . . Tuiskunen-Bäck, A. (2024). Hybrid capture-based next-generation sequencing of new and old world Orthohantavirus strains and wild-type Puumala isolates from humans and bank voles. Journal of Clinical Virology, 172, Article ID 105672.
Open this publication in new window or tab >>Hybrid capture-based next-generation sequencing of new and old world Orthohantavirus strains and wild-type Puumala isolates from humans and bank voles
Show others...
2024 (English)In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 172, article id 105672Article in journal (Refereed) Published
Abstract [en]

Orthohantaviruses, transmitted primarily by rodents, cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas. These viruses, with documented human-to-human transmission, exhibit a wide case-fatality rate, 0.5–40 %, depending on the virus species, and no vaccine or effective treatment for severe Orthohantavirus infections exists. In Europe, the Puumala virus (PUUV), carried by the bank vole Myodes glareolus, causes a milder form of HFRS. Despite the reliance on serology and PCR for diagnosis, the three genomic segments of Swedish wild-type PUUV have yet to be completely sequenced.

We have developed a targeted hybrid-capture method aimed at comprehensive genomic sequencing of wild-type PUUV isolates and the identification of other Orthohantaviruses. Our custom-designed panel includes >11,200 probes covering the entire Orthohantavirus genus. Using this panel, we sequenced complete viral genomes from bank vole lung tissue, human plasma samples, and cell-cultured reference strains. Analysis revealed that Swedish PUUV isolates belong to the Northern Scandinavian lineage, with nucleotide diversity ranging from 2.8 % to 3.7 % among them. Notably, no significant genotypic differences were observed between the viral sequences from reservoirs and human cases except in the nonstructural protein.

Despite the high endemicity of PUUV in Northern Sweden, these are the first complete Swedish wild-type PUUV genomes and substantially increase our understanding of PUUV evolution and epidemiology. The panel's sensitivity enables genomic sequencing of human samples with viral RNA levels reflecting the natural progression of infection and underscores our panel's diagnostic value, and could help to uncover novel Orthohantavirus transmission routes.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Targeted sequencing, Whole-genome sequencing, Puumala virus, Orthohantaviruses, Hemorrhagic fever with renal syndrome, Diagnostics
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-223355 (URN)10.1016/j.jcv.2024.105672 (DOI)38574565 (PubMedID)2-s2.0-85189510700 (Scopus ID)
Funder
Swedish Research Council, 2020-06235Lars Hierta Memorial Foundation, FO2021-0251O.E. och Edla Johanssons vetenskapliga stiftelseRegion Västerbotten, RV-970009Region Västerbotten, RV-982503Stiftelsen Seth M. Kempes Minnes Stipendiefond, SMK21-0039
Available from: 2024-04-15 Created: 2024-04-15 Last updated: 2024-04-16Bibliographically approved
Wigren, J., Vikström, L., Rosendal, E., Gröning, R., Gwon, Y.-D., Nilsson, E., . . . Forsell, M. N. E. (2023). At-home sampling to meet geographical challenges for serological assessment of SARS-CoV-2 exposure in a rural region of northern Sweden, March to May 2021: a retrospective cohort study. Eurosurveillance, 28(13), Article ID 2200432.
Open this publication in new window or tab >>At-home sampling to meet geographical challenges for serological assessment of SARS-CoV-2 exposure in a rural region of northern Sweden, March to May 2021: a retrospective cohort study
Show others...
2023 (English)In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 28, no 13, article id 2200432Article in journal (Refereed) Published
Abstract [en]

Background: The current SARS-CoV-2 pandemic has highlighted a need for easy and safe blood sampling in combination with accurate serological methodology. Venipuncture for testing is usually performed by trained staff at healthcare centres. Long travel distances to healthcare centres in rural regions may introduce a bias of testing towards relatively large communities with closer access. Rural regions are therefore often not represented in population-based data.

Aim: The aim of this retrospective cohort study was to develop and implement a strategy for at-home testing in a rural region of Sweden during spring 2021, and to evaluate its role to provide equal health care for its inhabitants.

Methods: We developed a sensitive method to measure antibodies to the S-protein of SARS-CoV-2 and optimised this assay for clinical use together with a strategy of at-home capillary blood sampling.

Results: We demonstrated that our ELISA gave comparable results after analysis of capillary blood or serum from SARS-CoV-2-experienced individuals. We demonstrated stability of the assay under conditions that reflected temperature and humidity during winter or summer. By assessment of capillary blood samples from 4,122 individuals, we could show both feasibility of the strategy and that implementation shifted the geographical spread of testing in favour of rural areas.

Conclusion: Implementation of at-home sampling enabled citizens living in remote rural areas access to centralised and sensitive laboratory antibody tests. The strategy for testing used here could therefore enable disease control authorities to get rapid access to information concerning immunity to infectious diseases, even across vast geographical distance.

Place, publisher, year, edition, pages
European Centre for Disease Control and Prevention (ECDC), 2023
Keywords
coronavirus disease (COVID-19), laboratory, surveillance, Sweden
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-206673 (URN)10.2807/1560-7917.ES.2023.28.13.2200432 (DOI)000971868200003 ()36995373 (PubMedID)2-s2.0-85151573640 (Scopus ID)
Available from: 2023-04-14 Created: 2023-04-14 Last updated: 2023-09-05Bibliographically approved
Blom, K., Fjällström, P., Molnár, C., Åberg, M., Vikström, L., Wigren, J., . . . Johansson, A. (2023). SARS-CoV-2-related mortality decrease in nursing home residents given multiple COVID-19 boosters [Letter to the editor]. The Lancet - Infectious diseases, 23(10), e393-e394
Open this publication in new window or tab >>SARS-CoV-2-related mortality decrease in nursing home residents given multiple COVID-19 boosters
Show others...
2023 (English)In: The Lancet - Infectious diseases, ISSN 1473-3099, E-ISSN 1474-4457, Vol. 23, no 10, p. e393-e394Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-215072 (URN)10.1016/S1473-3099(23)00548-0 (DOI)37716359 (PubMedID)2-s2.0-85172367341 (Scopus ID)
Available from: 2023-10-13 Created: 2023-10-13 Last updated: 2024-01-17Bibliographically approved
Vikström, L., Fjällström, P., Gwon, Y.-D., Sheward, D. J., Wigren-Byström, J., Evander, M., . . . Forsell, M. N. E. (2023). Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern: an observational study. The Lancet Regional Health: Europe, 30, Article ID 100646.
Open this publication in new window or tab >>Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern: an observational study
Show others...
2023 (English)In: The Lancet Regional Health: Europe, E-ISSN 2666-7762, Vol. 30, article id 100646Article in journal (Refereed) Published
Abstract [en]

Background: To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal COVID-19 among nursing homes residents.

Methods: We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort of nursing home residents in Sweden. We analyzed immunological and registry data from 16 September 2021 to 31 August 2022 with follow-up of deaths to 30 September 2022. The study period included implementation of the 3rd and 4th mRNA monovalent vaccine doses and Omicron virus waves.

Findings: A total of 3012 nursing home residents with median age 86 were enrolled. The 3rd mRNA dose elicited a 99-fold relative increase of S-binding IgG in blood and corresponding increase of neutralizing antibodies. The 4th mRNA vaccine dose boosted levels 3.8-fold. Half-life of S-binding IgG was 72 days. A total 528 residents acquired their first SARS-CoV-2 infection after the 3rd or the 4th vaccine dose and the associated 30-day mortality was 9.1%. We found no indication that levels of vaccine-induced antibodies protected against infection with Omicron VOCs. In contrast, the risk of death was inversely correlated to levels of S-directed IgG below the 20th percentile. The death risk plateaued at population average above the lower 35th percentile of S-binding IgG.

Interpretation: In the absence of neutralizing antibodies that protect from infection, quantification of S-binding IgG post vaccination may be useful to identify the most vulnerable for fatal COVID-19 among the oldest and frailest. This information is of importance for future strategies to protect vulnerable populations against neutralization resistant variants of concern.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Correlate of protection, COVID-19, Immune monitoring of vulnerable populations, Longevity of vaccination, Open cohort study, Vaccination, Vulnerable population
National Category
Infectious Medicine Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-208263 (URN)10.1016/j.lanepe.2023.100646 (DOI)2-s2.0-85156247971 (Scopus ID)
Funder
Swedish Research CouncilScience for Life Laboratory, SciLifeLabKnut and Alice Wallenberg FoundationVinnovaSwedish Association of Local Authorities and RegionsFamiljen Erling-Perssons Stiftelse
Available from: 2023-05-24 Created: 2023-05-24 Last updated: 2023-07-14Bibliographically approved
Tuiskunen-Bäck, A., Rasmuson, J., Thunberg, T., Rankin, G., Wigren Byström, J., Andersson, C., . . . Ahlm, C. (2022). Clinical and genomic characterisation of a fatal Puumala orthohantavirus case with low levels of neutralising antibodies. Infectious Diseases, 54(10), 766-772
Open this publication in new window or tab >>Clinical and genomic characterisation of a fatal Puumala orthohantavirus case with low levels of neutralising antibodies
Show others...
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.

Keywords
Icatibant, Puumala orthohantavirus, neutralising antibodies, orthohantavirus, viral load, virus sequence
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-201272 (URN)10.1080/23744235.2022.2076904 (DOI)000812658600001 ()35713235 (PubMedID)2-s2.0-85132173959 (Scopus ID)
Funder
Region Västerbotten, RV-938855Region Västerbotten, RV-734361Swedish Heart Lung Foundation, 2017-0334Swedish Research Council, 2020-06235Lars Hierta Memorial Foundation, FO2018- 0470
Available from: 2022-11-25 Created: 2022-11-25 Last updated: 2022-11-28Bibliographically approved
Ljungquist, O., Lundgren, M., Iliachenko, E., Månsson, F., Böttiger, B., Landin-Olsson, M., . . . Holm, K. (2022). Convalescent plasma treatment in severely immunosuppressed patients hospitalized with COVID-19: an observational study of 28 cases. Infectious Diseases, 54(4), 283-291
Open this publication in new window or tab >>Convalescent plasma treatment in severely immunosuppressed patients hospitalized with COVID-19: an observational study of 28 cases
Show others...
2022 (English)In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 54, no 4, p. 283-291Article in journal (Refereed) Published
Abstract [en]

Background: Immunosuppressed patients are particularly vulnerable to severe infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), risking prolonged viremia and symptom duration. In this study we describe clinical and virological treatment outcomes in a heterogeneous group of patients with severe immunosuppression due to various causes suffering from COVID-19 infection, who were all treated with convalescent plasma (CCP) along with standard treatment.

Methods: We performed an observational, retrospective case series between May 2020 to March 2021 at three sites in Skåne, Sweden, with a population of nearly 1.4 million people. All patients hospitalized for COVID-19 who received CCP with the indication severe immunosuppression as defined by the treating physician were included in the study (n = 28).

Results: In total, 28 severely immunocompromised patients, half of which previously had been treated with rituximab, who had received in-hospital convalescent plasma treatment of COVID-19 were identified. One week after CCP treatment, 13 of 28 (46%) patients had improved clinically defined as a decrease of at least one point at the WHO-scale. Three patients had increased score points of whom two had died. For 12 patients, the WHO-scale was unchanged.

Conclusion: As one of only few studies on CCP treatment of COVID-19 in hospitalized patients with severe immunosuppression, this study adds descriptive data. The study design prohibits conclusions on safety and efficacy, and the results should be interpreted with caution. Prospective, randomized trials are needed to investigate this further.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2022
Keywords
Antibodies, convalescent plasma, COVID-19, immunosuppression, lymphoma, pandemic, PCR, rituximab, SARS-CoV-2
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-190857 (URN)10.1080/23744235.2021.2013528 (DOI)000728648300001 ()34878955 (PubMedID)2-s2.0-85121359656 (Scopus ID)
Available from: 2021-12-29 Created: 2021-12-29 Last updated: 2023-04-25Bibliographically approved
Mittler, E., Wec, A. Z., Tynell, J., Guardado-Calvo, P., Wigren, J., Polanco, L. C., . . . Chandran, K. (2022). Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses. Science Translational Medicine, 14(636), Article ID eabl5399.
Open this publication in new window or tab >>Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses
Show others...
2022 (English)In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 14, no 636, article id eabl5399Article in journal (Refereed) Published
Abstract [en]

The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.

Place, publisher, year, edition, pages
American Association for the Advancement of Science, 2022
National Category
Microbiology in the medical area Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-193408 (URN)10.1126/scitranslmed.abl5399 (DOI)000772459100003 ()35294259 (PubMedID)2-s2.0-85126716233 (Scopus ID)
Funder
Swedish Research Council, 2020-06235Region Västerbotten, LL-579011
Available from: 2022-03-31 Created: 2022-03-31 Last updated: 2023-09-05Bibliographically approved
Beser, J., Galanis, I., Enkirch, T., Kühlmann Berenzon, S., van Straten, E., Duracz, J., . . . Bråve, A. (2022). Seroprevalence of SARS-CoV-2 in Sweden, April 26 to May 9, 2021. Scientific Reports, 12(1), Article ID 10816.
Open this publication in new window or tab >>Seroprevalence of SARS-CoV-2 in Sweden, April 26 to May 9, 2021
Show others...
2022 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 10816Article in journal (Refereed) Published
Abstract [en]

A national point seroprevalence study of SARS-CoV-2 was conducted in Sweden in April–May 2021. In total, 2860 individuals 3 to 90 years old from a probability-based web panel were included. Results showed that an estimated 32.6% of the population in Sweden had detectable levels of antibodies, and among non-vaccinated 20.1% had detectable levels of antibodies. We tested for differences in seroprevalence between age groups and by sex and estimated seroprevalence among previously infected participants by time since reporting.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-203320 (URN)10.1038/s41598-022-15183-w (DOI)000815641500016 ()35752708 (PubMedID)2-s2.0-85132991961 (Scopus ID)
Funder
Public Health Agency of Sweden , S2020/0281/FSPublic Health Agency of Sweden , S2020/08532 FS
Available from: 2023-01-18 Created: 2023-01-18 Last updated: 2023-01-18Bibliographically approved
Holm, K., Lundgren, M. N., Kjeldsen-Kragh, J., Ljungquist, O., Böttiger, B., Wikén, C., . . . Rasmussen, M. (2021). Convalescence plasma treatment of COVID-19: results from a prematurely terminated randomized controlled open-label study in Southern Sweden. BMC Research Notes, 14(1), Article ID 440.
Open this publication in new window or tab >>Convalescence plasma treatment of COVID-19: results from a prematurely terminated randomized controlled open-label study in Southern Sweden
Show others...
2021 (English)In: BMC Research Notes, E-ISSN 1756-0500, Vol. 14, no 1, article id 440Article in journal (Refereed) Published
Abstract [en]

Objective: Convalescent plasma has been tried as therapy for various viral infections. Early observational studies of convalescent plasma treatment for hospitalized COVID-19 patients were promising, but randomized controlled studies were lacking at the time. The objective of this study was to investigate if convalescent plasma is beneficial to hospitalized patients with COVID-19.

Results: Hospitalized patients with confirmed COVID-19 and an oxygen saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to standard of care or standard of care only. The primary outcome was number of days of oxygen treatment to keep saturation above 93% within 28 days from inclusion. The study was prematurely terminated when thirty-one of 100 intended patients had been included. The median time of oxygen treatment among survivors was 11 days (IQR 6–15) for the convalescent plasma group and 7 days (IQR 5–9) for the standard of care group (p = 0.4, median difference -4). Two patients in the convalescent plasma group and three patients in the standard of care group died (p = 0.64, OR 0.49, 95% CI 0.08–2.79). Thus no significant differences were observed between the groups.

Place, publisher, year, edition, pages
BioMed Central, 2021
Keywords
Convalescent plasma, COVID-19, Desaturation, Oxygen therapy, SARS-CoV2
National Category
Infectious Medicine Anesthesiology and Intensive Care
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-190414 (URN)10.1186/s13104-021-05847-7 (DOI)000726267300001 ()34863304 (PubMedID)2-s2.0-85120748357 (Scopus ID)
Available from: 2021-12-17 Created: 2021-12-17 Last updated: 2024-01-17Bibliographically approved
Organisations

Search in DiVA

Show all publications