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  • 1.
    Beser, Jessica
    et al.
    Public Health Agency of Sweden, Solna, Sweden; European Centre for Disease Prevention and Control (ECDC), European Public Health Microbiology Training Programme (EUPHEM), Solna, Sweden.
    Galanis, Ilias
    Public Health Agency of Sweden, Solna, Sweden.
    Enkirch, Theresa
    Public Health Agency of Sweden, Solna, Sweden.
    Kühlmann Berenzon, Sharon
    Public Health Agency of Sweden, Solna, Sweden.
    van Straten, Edward
    Public Health Agency of Sweden, Solna, Sweden.
    Duracz, Jan
    Public Health Agency of Sweden, Solna, Sweden.
    Rapp, Marie
    Public Health Agency of Sweden, Solna, Sweden.
    Zakikhany, Katherina
    Public Health Agency of Sweden, Solna, Sweden.
    Mansjö, Mikael
    Public Health Agency of Sweden, Solna, Sweden.
    Wigren, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Groenheit, Ramona
    Public Health Agency of Sweden, Solna, Sweden.
    Tegmark Wisell, Karin
    Public Health Agency of Sweden, Solna, Sweden.
    Bråve, Andreas
    Public Health Agency of Sweden, Solna, Sweden.
    Seroprevalence of SARS-CoV-2 in Sweden, April 26 to May 9, 20212022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 10816Article in journal (Refereed)
    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.

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  • 2.
    Blom, Kim
    et al.
    Public Health Agency of Sweden, Sweden.
    Fjällström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Molnár, Christian
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Familjeläkarna AB, Stockholm, Sweden.
    Åberg, Mikael
    Department of Medical Sciences, Clinical Chemistry and SciLifeLab Affinity Proteomics, Uppsala University, Uppsala, Sweden.
    Vikström, Linnea
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Wigren, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Bennet, Louise
    Clinical Studies Sweden, Forum South, Skåne University Hospital and Department of Clinical Sciences, Lund University, Lund, Sweden.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Rasmussen, Gunlög
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Klingström, Jonas
    Department of Biomedical Clinical Sciences, Linköping University, Linköping, Sweden.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    SARS-CoV-2-related mortality decrease in nursing home residents given multiple COVID-19 boosters2023In: The Lancet - Infectious diseases, ISSN 1473-3099, E-ISSN 1474-4457, Vol. 23, no 10, p. e393-e394Article in journal (Other academic)
  • 3.
    Holm, Karin
    et al.
    Department of Infectious diseases, Skåne University Hospital, Lund, Sweden.
    Lundgren, Maria N.
    Department of Clinical Immunology and Transfusion Medicine, University and Regional Laboratories, Region Skåne, Sweden.
    Kjeldsen-Kragh, Jens
    Department of Clinical Immunology and Transfusion Medicine, University and Regional Laboratories, Region Skåne, Sweden.
    Ljungquist, Oskar
    Clinical Infection Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden.
    Böttiger, Blenda
    Department of Clinical Microbiology, University and Regional Laboratories, Region Skåne, Sweden.
    Wikén, Christian
    Department of Infectious diseases, Skåne University Hospital, Lund, Sweden.
    Öberg, Jonas
    Department of Infectious diseases, Skåne University Hospital, Lund, Sweden.
    Fernström, Nils
    Department of Infectious diseases, Skåne University Hospital, Lund, Sweden.
    Rosendal, Ebba
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Wigren, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Landin-Olsson, Mona
    Department of Endocrinology, Skåne University Hospital, Lund, Sweden.
    Rasmussen, Magnus
    Department of Infectious diseases, Skåne University Hospital, Lund, Sweden.
    Convalescence plasma treatment of COVID-19: results from a prematurely terminated randomized controlled open-label study in Southern Sweden2021In: BMC Research Notes, E-ISSN 1756-0500, Vol. 14, no 1, article id 440Article in journal (Refereed)
    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.

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  • 4.
    Kerkman, Priscilla
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Dernstedt, Andy
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Tadala, Lalitha
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Mittler, Eva
    Dannborg, Mirjam
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Sundling, Christopher
    Maleki, Kimia T.
    Tauriainen, Johanna
    Tuiskunen-Bäck, Anne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Wigren Byström, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Ocaya, Pauline
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Thunberg, Therese
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Jangra, Rohit K
    Román-Sosa, Gleyder
    Guardado-Calvo, Pablo
    Rey, Feilx A.
    Klingström, Jonas
    Chandran, Kartik
    Puhar, Andrea
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Generation of plasma cells and CD27-IgD- B cells during hantavirus infection is associated with distinct pathological findings2021In: Clinical & Translational Immunology (CTI), E-ISSN 2050-0068, Vol. 10, article id e1313Article in journal (Refereed)
    Abstract [en]

    Objective: Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms arenot fully understood, nor if they affect the humoral immune system. The objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction.

    Methods: We performed a comprehensive characterisation of longitudinal antiviral B-cell responses of 26 hantavirus patients and combined this with paired clinical data. In addition, we measured extracellular adenosine triphosphate (ATP)and its breakdown products in circulation and performed in vitro stimulations to address its effect on B cells.

    Results: We found that thrombocytopenia was correlated to an elevated frequency of plasmablasts in circulation. In contrast, kidney dysfunction was indicative of an accumulation of CD27-IgD- B cells and CD27/low plasmablasts. Finally, we provide evidence that high levels of extracellular ATP and matrix metalloproteinase 8 can contribute to shedding of CD27 during human hantavirus infection.

    Conclusion:  Our findings demonstrate that thrombocytopenia and kidneydysfunction associate with distinctly different effects on the humoral immune system. Moreover, hantavirus-infectedindividuals have significantly elevated levels of extracellular ATP incirculation.

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  • 5.
    Kerkman, Priscilla
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Tuiskunen-Bäck, Anne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Dernstedt, Andy
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Wigren, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    The B cell response towards Puumala virus infection: can B cells be infected?2017In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, no 4, p. 260-260Article in journal (Other academic)
    Abstract [en]

    Hantavirus infections are rodent-borne viruses causing potential lethal infections in humans. Different hantaviruses exist worldwide, reporting a fatality rate of up to 40%. The Puumala hantavirus (PUUV) is endemic in northern Sweden. This hantavirus strain has a relatively low fatality rate but the hospitalisation rate is high. No vaccine to the virus and no treatment for the disease exist. Despite differences in severity, the immune-mediated pathogenesis of Puumala virus infection is similar to that of highly lethal strains of hantavirus. It is currently unknown how the humoral immune system is affected during hantavirus infection.

    The aim of this study is to characterise how the humoral immune response is affected during Puumala virus infection. A large number of longitudinal patient samples have been collected. Here, we demonstrate the longitudinal kinetics of the B cell response during Puumala virus infection and show that there is a change in B cell populations during the course of the disease. Furthermore we show that B cells carry known hantavirus receptors. This suggests that Puumala virus may directly infect B cells. Infection of the B cells could affect their function and or phenotype explaining a different immune response. Importantly, in approximately 10–15% of Puumala infected patients we could detect antibodies that could neutralise other hantaviruses in vitro. Samples from these patients could help to generate a monoclonal antibody treatment potentially treating diseases caused by several hantavirus.

  • 6.
    Lagerqvist, Nina
    et al.
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
    Maleki, Kimia T.
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Verner-Carlsson, Jenny
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
    Olausson, Mikaela
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
    Dillner, Joakim
    Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wigren Byström, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Monsen, Tor J.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Eriksson, Jenny
    Region Västmanland, Västerås, Sweden.
    Bogdanovic, Gordana
    Karolinska University Hospital, Stockholm, Sweden.
    Muschiol, Sandra
    Karolinska University Hospital, Stockholm, Sweden.
    Ljunggren, Joel
    Region Västernorrland, County Hospital of Västernorrland, Sundsvall, Sweden.
    Repo, Johanna
    Region Västernorrland, County Hospital of Västernorrland, Sundsvall, Sweden.
    Kjerstadius, Torbjörn
    Region Värmland, Centralsjukhuset, Karlstad, Sweden.
    Muradrasoli, Shaman
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
    Brytting, Mia
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
    Szekely Björndal, Åsa
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
    Åkerlund, Thomas
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
    Nilsson, Charlotta
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Klingström, Jonas
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Evaluation of 11 SARS-CoV-2 antibody tests by using samples from patients with defined IgG antibody titers2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 7614Article in journal (Refereed)
    Abstract [en]

    We evaluated the performance of 11 SARS-CoV-2 antibody tests using a reference set of heat-inactivated samples from 278 unexposed persons and 258 COVID-19 patients, some of whom contributed serial samples. The reference set included samples with a variation in SARS-CoV-2 IgG antibody titers, as determined by an in-house immunofluorescence assay (IFA). The five evaluated rapid diagnostic tests had a specificity of 99.0% and a sensitivity that ranged from 56.3 to 81.6% and decreased with low IFA IgG titers. The specificity was > 99% for five out of six platform-based tests, and when assessed using samples collected ≥ 22 days after symptom onset, two assays had a sensitivity of > 96%. These two assays also detected samples with low IFA titers more frequently than the other assays. In conclusion, the evaluated antibody tests showed a heterogeneity in their performances and only a few tests performed well with samples having low IFA IgG titers, an important aspect for diagnostics and epidemiological investigations.

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  • 7.
    Ljungquist, Oskar
    et al.
    Department of Translational Medicine, Clinical Infection Medicine, Faculty of Medicine, Lund University, Malmö, Sweden; Department of Infectious Diseases, Helsingborg Hospital, Helsingborg, Sweden.
    Lundgren, Maria
    Department of Clinical Immunology and Transfusion Medicine, Office of Medical Services, Lund, Sweden.
    Iliachenko, Elena
    Department of Clinical Immunology and Transfusion Medicine, Office of Medical Services, Lund, Sweden.
    Månsson, Fredrik
    Department of Translational Medicine, Clinical Infection Medicine, Faculty of Medicine, Lund University, Malmö, Sweden; Skåne University Hospital, Malmö, Sweden.
    Böttiger, Blenda
    Department of Clinical Microbiology, University and Regional Laboratories, Lund, Sweden.
    Landin-Olsson, Mona
    Skåne University Hospital, Malmö, Sweden; Department of Clinical Science, Division of Internal Medicine, Lund University, Lund, Sweden.
    Wikén, Christian
    Skåne University Hospital, Malmö, Sweden; Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden.
    Rosendal, Ebba
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Wigren, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Kjeldsen-Kragh, Jens
    Department of Clinical Immunology and Transfusion Medicine, Office of Medical Services, Lund, Sweden.
    Rasmussen, Magnus
    Skåne University Hospital, Malmö, Sweden; Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden.
    Kahn, Fredrik
    Skåne University Hospital, Malmö, Sweden; Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden.
    Holm, Karin
    Skåne University Hospital, Malmö, Sweden; Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden.
    Convalescent plasma treatment in severely immunosuppressed patients hospitalized with COVID-19: an observational study of 28 cases2022In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 54, no 4, p. 283-291Article in journal (Refereed)
    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.

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  • 8.
    Maleki, Kimia T.
    et al.
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Tauriainen, Johanna
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    García, Marina
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Kerkman, Priscilla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Christ, Wanda
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Dias, Joana
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Wigren, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Leeansyah, Edwin
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, China; Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ljunggren, Hans-Gustaf
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Björkström, Niklas K.
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Sandberg, Johan K.
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Klingström, Jonas
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    MAIT cell activation is associated with disease severity markers in acute hantavirus infection2021In: Cell Reports Medicine, E-ISSN 2666-3791 , Vol. 2, no 3, article id 100220Article in journal (Refereed)
    Abstract [en]

    Hantaviruses are zoonotic RNA viruses that cause severe acute disease in humans. Infected individuals have strong inflammatory responses that likely cause immunopathology. Here, we studied the response of mucosal-associated invariant T (MAIT) cells in peripheral blood of individuals with hemorrhagic fever with renal syndrome (HFRS) caused by Puumala orthohantavirus, a hantavirus endemic in Europe. We show that MAIT cell levels decrease in the blood during HFRS and that residual MAIT cells are highly activated. This activation correlates with HFRS severity markers. In vitro activation of MAIT cells by hantavirus-exposed antigen-presenting cells is dependent on type I interferons (IFNs) and independent of interleukin-18 (IL-18). These findings highlight the role of type I IFNs in virus-driven MAIT cell activation and suggest a potential role of MAIT cells in the disease pathogenesis of viral infections.

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  • 9.
    Mittler, Eva
    et al.
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
    Wec, Anna Z.
    Adimab, LLC, United States.
    Tynell, Janne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland.
    Guardado-Calvo, Pablo
    Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France.
    Wigren, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Polanco, Laura C.
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
    O'Brien, Cecilia M.
    U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States; The Geneva Foundation, Tacoma, WA 98402, USA.
    Slough, Megan M.
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
    Abelson, Dafna M.
    Mapp Biopharmaceutical Inc., San Diego, CA 92121, USA.
    Serris, Alexandra
    Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France.
    Sakharkar, Mrunal
    Adimab, LLC, United States.
    Pehau-Arnaudet, Gerard
    Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France.
    Bakken, Russell R.
    U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States.
    Geoghegan, James C.
    Adimab, LLC, United States.
    Jangra, Rohit K.
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
    Keller, Markus
    Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany.
    Zeitlin, Larry
    Mapp Biopharmaceutical Inc., San Diego, CA 92121, USA.
    Vapalahti, Olli
    Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland; Veterinary Biosciences, Veterinary Faculty, University of Helsinki, Helsinki, Finland.
    Ulrich, Rainer G.
    Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany; Deutsches Zentrum für Infektionsforschung, Partner site Hamburg-Lübeck- Borstel-Riems, Greifswald-Insel Riems, Germany.
    Bornholdt, Zachary A.
    Mapp Biopharmaceutical Inc., San Diego, CA 92121, USA.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Rey, Felix A.
    Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France.
    Dye, John M.
    U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States.
    Bradfute, Steven B.
    Center for Global Health, Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, United States.
    Strandin, Tomas
    Zoonosis Unit, Department of Virology, Medical Faculty, University of Helsinki, Helsinki, Finland.
    Herbert, Andrew S.
    U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, United States; The Geneva Foundation, Tacoma, WA 98402, USA.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Walker, Laura M.
    Adimab, LLC, United States.
    Chandran, Kartik
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
    Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses2022In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 14, no 636, article id eabl5399Article in journal (Refereed)
    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.

  • 10.
    Rankin, Gregory
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Byström, Julia Wigren
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Gustafsson, Rasmus
    Hansson, Magnus
    Thunberg, Therese
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Connolly, Anne-Marie Fors
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    MMP9 Associates with Endothelial Glycocalyx Degradation During Haemorrhagic Fever with Renal Syndrome2019In: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 56, p. 35-35Article in journal (Other academic)
    Abstract [en]

    Introduction: Haemorrhagic fever with renal syndrome (HFRS) is characterized by fever, hypotension, vascular leakage, thrombocytopenia and renal failure. HFRS in Sweden is caused by the Puumala hantavirus and is spread by viral-infested droppings from bank voles. The health care system has little to offer these patients since there is no antiviral treatment and as of yet there is no vaccine prophylaxis available. We previously showed that a marker of endothelial glycocalyx degradation (Syndecan-1) was associated with disease severity and disseminated intravascular coagulation during HFRS (Connolly-Andersen et al., 2014, Open Forum Infect Dis.).

    Methods: We analysed the levels of other endothelial glycocalyx degradation markers (heparan sulfate, soluble thrombomodulin, albumin), a potential “sheddase”: Matrix Metalloproinase 9 (MMP9) and neutrophil activation/tissue damage (neutrophil gelatinase-associated lipocalin, NGAL) in patient plasma from 44 HFRS patients collected consecutively following disease onset. We used the generalized estimating equation to analyse the association between endothelial glycocalyx degradation, MMP9 levels, neutrophil activation/tissue damage and HFRS disease outcome (need for oxygen, transfusion with blood components, need for intensive care unit (ICU) treatment and renal damage).

    Results: 44 HFRS patients were included in this study (29 females (66%)); need for oxygen: 11 (25%); transfusion with blood components: 3 (7%) and stay at ICU: 2 (5%)). The levels of MMP9 were significantly associated with all markers of endothelial glycocalyx degradation. Neutrophil activation/tissue damage (NGAL) was also significantly associated with MMP9 and endothelial glycocalyx degradation markers (apart from albumin (p = 0.053). In addition degradation of endothelial glycocalyx associated with HFRS disease outcome.

    Conclusion: Degradation of the endothelial glycocalyx could be a potential mechanism of HFRS pathogenesis, and potentially MMP9 could contribute to degradation of the endothelial glycocalyx

  • 11.
    Rosenbaum, William
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Bovinder Ylitalo, Erik
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Castel, Guillaume
    CBGP, INRAE, CIRAD, Institut Agro, IRD, Univ Montpellier, Montpellier, France.
    Sjödin, Andreas
    CBRN Security and Defence, Swedish Defence Research Agency - FOI, Umeå, Sweden.
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Wigren Byström, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Pettersson, Lisa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Tuiskunen-Bäck, Anne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Hybrid capture-based next-generation sequencing of new and old world Orthohantavirus strains and wild-type Puumala isolates from humans and bank voles2024In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 172, article id 105672Article in journal (Refereed)
    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.

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  • 12.
    Tuiskunen-Bäck, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Rasmuson, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Thunberg, Therese
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Rankin, Gregory
    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.
    Wigren Byström, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Andersson, Charlotta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sjödin, Andreas
    CBRN Security and Defence, Swedish Defence Research Agency - FOI, Umeå, Sweden.
    Forsell, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Clinical and genomic characterisation of a fatal Puumala orthohantavirus case with low levels of neutralising antibodies2022In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 54, no 10, p. 766-772Article in journal (Refereed)
    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.

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  • 13.
    Vikström, Linnea
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Fjällström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Gwon, Yong-Dae
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Sheward, Daniel J.
    The Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
    Wigren-Byström, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Bladh, Oscar
    The Department of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Molnar, Christian
    Familjeläkarna, Stockholm, Sweden.
    Rasmussen, Gunlög
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Bennet, Louise
    Department of Clinical Sciences, Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund University, Lund, Sweden.
    Åberg, Mikael
    The Department of Medical Sciences, Clinical Chemistry and SciLifeLab, Uppsala University, Uppsala, Sweden.
    Björk, Jonas
    The Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Tevell, Staffan
    Faculty of Medicine and Health, The Department of Infectious Diseases, Karlstad Hospital and Centre for Clinical Research and Education, Region Värmland, Örebro University, Örebro, Sweden.
    Thålin, Charlotte
    The Department of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden.
    Blom, Kim
    The Swedish Public Health Agency, Stockholm, Sweden.
    Klingström, Jonas
    The Department of Biomedical Clinical Sciences, Linköpings University, Linköping, Sweden.
    Murrell, Ben
    The Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Johansson, Anders F.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Vaccine-induced correlate of protection against fatal COVID-19 in older and frail adults during waves of neutralization-resistant variants of concern: an observational study2023In: The Lancet Regional Health: Europe, E-ISSN 2666-7762, Vol. 30, article id 100646Article in journal (Refereed)
    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.

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  • 14.
    Waltraud, Schrottmaier
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
    Schmuckenschlager, Anna
    Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
    Thunberg, Therese
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Wigren, Julia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Fors Connolly, Anne-Marie
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Assinger, Alice
    Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Direct and indirect effects of Puumala hantavirus on platelet function2024In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 233, p. 41-54Article in journal (Refereed)
    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.

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  • 15.
    Wigren Byström, Julia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Näslund, Jonas
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Trulsson, Fredrik
    Umeå University, Faculty of Science and Technology, European CBRNE Center. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wesula Lwande, Olivia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bucht, Göran
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Quantification and kinetics of viral RNA transcripts produced in Orthohantavirus infected cells2018In: Virology Journal, E-ISSN 1743-422X, Vol. 15, article id 18Article in journal (Refereed)
    Abstract [en]

    Background: Rodent borne viruses of the Orthohantavirus genus cause hemorrhagic fever with renal syndrome among people in Eurasia, and hantavirus cardiopulmonary syndrome in the Americas. At present, there are no specific treatments or efficient vaccines against these diseases. Improved understanding of viral transcription and replication may instigate targeted treatment of Orthohantavirus infections. For this purpose, we investigated the kinetics and levels of viral RNA transcription during an ongoing infection in-vitro.

    Methods: Vero E6 cells were infected with Puumala Orthohantavirus (strain Kazan) before cells and supernatants were collected at different time points post infection for the detection of viral RNAs. A plasmid containing primer binding sites of the three Orthohantavirus segments small (S), medium (M) and large (L) was constructed and standard curves were generated to calculate the copy numbers of the individual transcripts in the collected samples.

    Results: Our results indicated a rapid increase in the copy number of viral RNAs after 9 h post infection. At peak days, 2-6 days after infection, the S- and M-segment transcripts became thousand and hundred-fold more abundant than the copy number of the L-segment RNA, respectively. The presence of viral RNA in the cell culture media was detected at later time-points.

    Conclusions: We have developed a method to follow RNA transcription in-vitro after synchronous infection of Vero cells. The obtained results may contribute to the understanding of the viral replication, and may have implications in the development of antiviral drugs targeting transcription or replication of negative stranded RNA viruses.

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  • 16.
    Wigren, Julia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Xerum AB, Umeå, Sweden.
    Vikström, Linnea
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Rosendal, Ebba
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Gröning, Remigius
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Gwon, Yong-Dae
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Nilsson, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Sharma, Atin
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Espaillat, Akbar
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Hanke, Leo
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    McInerney, Gerald
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Puhar, Andrea
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Cava, Felipe
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Karlsson Hedestam, Gunilla B.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Thunberg, Therese
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Johansson, Anders F.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    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 study2023In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 28, no 13, article id 2200432Article in journal (Refereed)
    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.

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