| 1. |
- Gröning, Remigius, et al.
(författare)
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Intravenous immunoglobulin therapy for COVID-19 in immunocompromised patients : A retrospective cohort study
- 2024
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Ingår i: International Journal of Infectious Diseases. - : Elsevier. - 1201-9712 .- 1878-3511. ; 144
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the effectiveness of intravenous immunoglobulin (IVIG) as treatment for COVID-19 in immunocompromised patients. Methods: This retrospective study investigated outcomes for immunocompromised, vaccine non-responsive, patients that between September 2022 and April 2023 received IVIG as treatment for COVID-19 in the region of Västerbotten, Sweden. We analyzed clinical data, viral load, and anti-SARS-CoV-2 IgG binding and neutralization levels of patient serum samples and IVIG production batches. Primary and secondary outcomes were clinical cure and viral clearance, respectively.Results: Sixteen patients were analyzed. After a median COVID-19 duration of 4 weeks, a median 60 g IVIG infusion increased SARS-CoV-2 binding and neutralizing antibody levels, with broad in vitro activity against tested variants. The treatment resulted in abrogation of viremia in all patients and general improvement in 15 survivors that all met the primary endpoint. Thirteen patients met the secondary endpoint at follow-up after a median of four months. Two subjects with persistent SARS-CoV-2 carriage relapsed but were successfully retreated with IVIG.Conclusions: Antibodies in IVIG efficiently neutralized several SARS-CoV-2 variants. Treatment with IVIG was associated with clinical cure and viral clearance in immunocompromised patients. Our data suggests that IVIG could be a novel treatment alternative for COVID-19 for this patient category.
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| 2. |
- Tuiskunen-Bäck, Anne, et al.
(författare)
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Clinical and genomic characterisation of a fatal Puumala orthohantavirus case with low levels of neutralising antibodies
- 2022
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 54:10, s. 766-772
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 3. |
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| 4. |
- Darelius, Anders, 1977, et al.
(författare)
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Fluid dynamics simulation of the high shear mixing process
- 2010
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Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947. ; 164:2-3, s. 418-424
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Tidskriftsartikel (refereegranskat)abstract
- The Eulerian-Eulerian two-fluid approach for modelling multiphase flows is used to simulate the flow in a high shear mixer. The results are compared with experimental velocity profiles for the solids phase at the wall in the mixer obtained using a high speed camera (Darelius et al. Chem. Eng. Sci. 62 (2007) 2366).The governing equations are closed using relations from the Kinetic Theory of Granular Flow (KTGF) combined with a frictional stress model due to Johnson and Jackson and Schaeffer and inter-phase drag due to Wen and Yu. In addition, calculations are presented for a model with a constant particle phase viscosity (CPV). Free slip and partial slip boundary conditions for the solid phase velocity at the vessel wall and the impeller have been utilized.The results show that the bed height could be well predicted by the partial slip model, whereas the free slip model could not capture the experimentally found bed height satisfactorily. For the KTGF model, the swirling motion of the rotating torus that is formed by the moving powder bed was over-predicted and the tangential wall velocity was under-predicted, probably due to the fact that the frictional stress model needs to be further developed, e.g. to tackle cohesive particles in dense flow. The CPV model gave predictions in good agreement with the experiments for a solids viscosity of 0.1. Pa. s and a wall slip parameter of 0.005. m/Pa. s. However, for a very low or very high value of the particle phase viscosity and for a high value of the wall slip parameter the agreement with experiments was poor. Interestingly, values of the viscosity that are commonly employed for fluidized beds seem applicable also in the present case. © 2009 Elsevier B.V.
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| 5. |
- Eidevåg, Tobias, 1987, et al.
(författare)
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Angle of repose of snow: An experimental study on cohesive properties
- 2022
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Ingår i: Cold Regions Science and Technology. - : Elsevier BV. - 0165-232X .- 1872-7441. ; 194
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Tidskriftsartikel (refereegranskat)abstract
- The angle of repose is a measure reflecting the internal friction and cohesion properties of a granular material. In this paper, we present an experimental setup and measurements for the angle of repose of snow for seven different snow samples over a large range of temperatures. The results show that the angle of repose is dependent on the fall height, the temperature, and the grain size of the snow. These variables are quantified, and their interdependencies are separately studied. With increased snow temperature, the angle of repose increases, and this can be explained by the presence of a liquid layer on ice that can be thermodynamically stable at temperatures below the melting point of water. With decreasing grain size the angle of repose also increases which is expected since the cohesive energy decreases more slowly than the grain mass. For increasing fall height, the snow grains generally accelerate to larger collisional velocities, yielding a smaller angle of repose. In general, the dimensionless cohesion number was found to largely reflect the dependencies of the variables and is therefore useful for understanding what affects the angle of repose. The results demonstrate that the drag force and collision dynamics of ice grains are important for understanding how snow accumulates on a surface, for example if one desires predicting snow accretion by simulating a dispersed cloud of snow. © 2021
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| 6. |
- Eidevåg, Tobias, 1987, et al.
(författare)
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Collisional damping of spherical ice particles
- 2021
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Ingår i: Powder Technology. - : Elsevier BV. - 0032-5910 .- 1873-328X. ; 383, s. 318-327
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents experimental values for the coefficient of restitution (e(n)) for millimeter-sized ice particles colliding with massive walls at different temperatures. Three different wall materials are tested: hardened glass, ice and Acrylonitrile butadiene styrene (ABS) polymer. The results show a high sensitivity to impact velocity V-i, where e(n) decreases rapidly with increasing V-i. The results also show a decrease in e(n) with increasing temperature T. A novel model that predicts e(n) based on the assumption of collisional melting and viscous damping caused by an increased premelted liquid-layer, is proposed. The model predicts both the velocity and the temperature trends seen in the experiments. The difference obtained in experiments between wall materials is also captured by the new model. A generalized regime map for ice particle collisions is proposed to combine the new model with previous work. (C) 2021 The Author(s).
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| 7. |
- Eidevåg, Tobias, 1987, et al.
(författare)
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Snow Contamination of Simplified Automotive Bluff Bodies: A Comparison between Wind Tunnel Experiments and Numerical Modeling
- 2022
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Ingår i: SAE Technical Paper Series. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 2641-9637 .- 0148-7191 .- 2688-3627.
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Konferensbidrag (refereegranskat)abstract
- We describe experiments and numerical modeling of snow surface contamination on two simplified automotive bluff bodies: The Ahmed body and a wedge. The purpose was twofold: 1) To obtain well defined experimental results of snow contamination on simple geometries; 2) To propose a numerical modeling approach for snow contamination. The experiments were performed in a climatic wind tunnel using a snow cannon at −15 °C and the results show that the snow accumulation depends on the aerodynamics of the studied bluff bodies. Snow accumulates on surfaces in proximity to the aerodynamic wakes of the bodies and characteristic snow patterns are obtained on side surfaces. The numerical modeling approach consisted of an aerodynamic setup coupled with Lagrangian particle tracking. Particles were determined to adhere or rebound depending on an adhesion model combined with a resuspension criterion. The adhesion model was based on adhesive-elastic contact theory and the resuspension criterion is derived from the balance between the aerodynamic forces acting on a particle and the critical force for onset of resuspension. The results show that the numerical method can predict certain characteristic snow patterns obtained from the experiments and we also highlight deviations obtained between experimental and simulation results. The simulation results show that the snow accumulation patterns on a bluff body will depend on the smallest ice particles in a snow sample which implies that samples with larger ice particle (for example natural snow) could produce different snow patterns than the fine machine-made snow used in this study.
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| 8. |
- Rasmuson, Johan, 1977-, et al.
(författare)
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Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection
- 2016
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 35:4, s. 713-721
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Tidskriftsartikel (refereegranskat)abstract
- Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8+ T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments.
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| 9. |
- Rasmuson, Johan, 1977-, et al.
(författare)
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Presence of activated airway T lymphocytes in human puumala hantavirus disease
- 2011
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Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 140:3, s. 715-722
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hantaviruses cause two clinical syndromes; hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The clinical spectrum in HFRS also often involves respiratory symptoms. As information of the pulmonary pathogenesis in HFRS is limited, we aimed to further study the local airway immune response in the lower airways.METHODS: In 15 hospitalized HFRS patients, bronchoscopy was performed with sampling of endobronchial mucosal biopsies and bronchoalveolar lavage (BAL) fluid. Biopsies were stained for leukocytes, lymphocyte subsets and vascular endothelial adhesion molecules. BAL fluid and blood lymphocyte subsets were determined using flow cytometry. Fourteen healthy volunteers acted as control group.RESULTS: Compared to controls, endobronchial mucosal biopsies from HFRS patients revealed increased numbers of CD8(+) T cells in both epithelium and submucosa (p≤0.001), along with an increase in submucosal CD4(+) T cells (p=0.001). In contrast, patients' submucosal neutrophil and eosinophil numbers were reduced (p<0.001). The expression of vascular cell adhesion molecule-1 (VCAM-1) was enhanced in HFRS patients (p<0.001). In HFRS patients, analyses of T cell subsets in BAL fluid showed higher proportions of CD3(+) and CD8(+) T cells (p=0.011 and p=0.025), NK cells (p<0.001) together with an increased expression of activation markers HLA-DR and CD25 on T cells (p<0.001 and p<0.001).CONCLUSIONS: The present findings indicate a local immune response in terms of activated T lymphocytes in the lungs of patients with HFRS. The elevated expression of activation markers and VCAM-1 further implies the importance of cytotoxic lymphocytes in the pathogenesis of pulmonary involvement in HFRS.
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| 10. |
- Rasmuson, Johan, 1977-, et al.
(författare)
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Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus
- 2011
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 30:5, s. 685-690
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Tidskriftsartikel (refereegranskat)abstract
- Hantaviruses have previously been recognised to cause two separate syndromes: hemorrhagic fever with renal syndrome in Eurasia, and hantavirus pulmonary syndrome (HPS) in the Americas. However, increasing evidence suggests that this dichotomy is no longer fruitful when recognising human hantavirus disease and understanding the pathogenesis. Herein are presented three cases of severe European Puumala hantavirus infection that meet the HPS case definition. The clinical and pathological findings were similar to those found in American hantavirus patients. Consequently, hantavirus infection should be considered as a cause of acute respiratory distress in all endemic areas worldwide.
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| 11. |
- Scholz, Saskia, et al.
(författare)
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Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways
- 2017
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Ingår i: PLoS Pathogens. - : Public library science. - 1553-7366 .- 1553-7374. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis. Here, we studied 17 patients infected with Puumala virus that causes a mild form of hemorrhagic fever with renal syndrome (HFRS). Bronchial biopsies as well as longitudinal blood draws were obtained from the patients. During the acute stage of disease, a significant influx of MNPs expressing HLA-DR, CD11c or CD123 was detected in the patients' bronchial tissue. In parallel, absolute numbers of MNPs were dramatically reduced in peripheral blood, coinciding with viremia. Expression of CCR7 on the remaining MNPs in blood suggested migration to peripheral and/or lymphoid tissues. Numbers of MNPs in blood subsequently normalized during the convalescent phase of the disease when viral RNA was no longer detectable in plasma. Finally, we exposed blood MNPs in vitro to Puumala virus, and demonstrated an induction of CCR7 expression on MNPs. In conclusion, the present study shows a marked redistribution of blood MNPs to the airways during acute hantavirus disease, a process that may underlie the local immune activation and contribute to immunopathogenesis in hantavirus-infected patients.
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| 12. |
- Sundén-Cullberg, Jonas, et al.
(författare)
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Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration.Methods: The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 μg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery.Results: Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly.Conclusion: Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020-00174824).
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