| 1. |
- Rosendal, Ebba, et al.
(author)
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Serine Protease Inhibitors Restrict Host Susceptibility to SARS-CoV-2 Infections
- 2022
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In: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 13:3
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Journal article (peer-reviewed)abstract
- The coronavirus disease 2019, COVID-19, is a complex disease with a wide range of symptoms from asymptomatic infections to severe acute respiratory syndrome with lethal outcome. Individual factors such as age, sex, and comorbidities increase the risk for severe infections, but other aspects, such as genetic variations, are also likely to affect the susceptibility to SARS-CoV-2 infection and disease severity. Here, we used a human 3D lung cell model based on primary cells derived from multiple donors to identity host factors that regulate SARS-CoV-2 infection. With a transcriptomics-based approach, we found that less susceptible donors show a higher expression level of serine protease inhibitors SERPINA1, SERPINE1, and SERPINE2, identifying variation in cellular serpin levels as restricting host factors for SARS-CoV-2 infection. We pinpoint their antiviral mechanism of action to inhibition of the cellular serine protease, TMPRSS2, thereby preventing cleavage of the viral spike protein and TMPRSS2-mediated entry into the target cells. By means of single-cell RNA sequencing, we further locate the expression of the individual serpins to basal, ciliated, club, and goblet cells. Our results add to the importance of genetic variations as determinants for SARS-CoV-2 susceptibility and suggest that genetic deficiencies of cellular serpins might represent risk factors for severe COVID-19. Our study further highlights TMPRSS2 as a promising target for antiviral intervention and opens the door for the usage of locally administered serpins as a treatment against COVID-19.
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| 2. |
- Gröning, Remigius, et al.
(author)
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Intravenous immunoglobulin therapy for COVID-19 in immunocompromised patients : A retrospective cohort study
- 2024
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In: International Journal of Infectious Diseases. - : Elsevier. - 1201-9712 .- 1878-3511. ; 144
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Journal article (peer-reviewed)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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| 3. |
- Näslund, Johan, 1954-, et al.
(author)
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Studerandes syn på grupparbete
- 2020
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In: Handbok för grupparbete. - Lund : Studentlitteratur AB. - 9789144132556 ; , s. 289-305
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Book chapter (other academic/artistic)
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| 4. |
- Ahmad, Irma, et al.
(author)
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High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19
- 2023
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In: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 11
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Journal article (peer-reviewed)abstract
- BACKGROUND: The long-term sequelae after COVID-19 constitute a challenge to public health and increased knowledge is needed. We investigated the prevalence of self-reported persistent symptoms and reduced health-related quality of life (HRQoL) in relation to functional exercise capacity, 6 months after infection, and explored risk factors for COVID-19 sequalae.METHODS: This was a prospective, multicenter, cohort study including 434 patients. At 6 months, physical exercise capacity was assessed by a 1-minute sit-to-stand test (1MSTST) and persistent symptoms were reported and HRQoL was evaluated through the EuroQol 5-level 5-dimension (EQ-5D-5L) questionnaire. Patients with both persistent symptoms and reduced HRQoL were classified into a new definition of post-acute COVID syndrome, PACS+. Risk factors for developing persistent symptoms, reduced HRQoL and PACS+ were identified by multivariable Poisson regression.RESULTS: Persistent symptoms were experienced by 79% of hospitalized, and 59% of non-hospitalized patients at 6 months. Hospitalized patients had a higher prevalence of self-assessed reduced overall health (28 vs. 12%) and PACS+ (31 vs. 11%). PACS+ was associated with reduced exercise capacity but not with abnormal pulse/desaturation during 1MSTST. Hospitalization was the most important independent risk factor for developing persistent symptoms, reduced overall health and PACS+.CONCLUSION: Persistent symptoms and reduced HRQoL are common among COVID-19 survivors, but abnormal pulse and peripheral saturation during exercise could not distinguish patients with PACS+. Patients with severe infection requiring hospitalization were more likely to develop PACS+, hence these patients should be prioritized for clinical follow-up after COVID-19.
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| 5. |
- Björsell, Tove, et al.
(author)
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Risk factors for impaired respiratory function post COVID-19 : A prospective cohort study of nonhospitalized and hospitalized patients
- 2023
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In: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Inc.. - 0954-6820 .- 1365-2796. ; 293:5, s. 600-614
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Journal article (peer-reviewed)abstract
- BACKGROUND: Severe COVID-19 increases the risk for long-term respiratory impairment, but data after mild COVID-19 are scarce. Our aims were to determine risk factors for reduced respiratory function 3-6 months after COVID-19 infection and to investigate if reduced respiratory function would relate to impairment of exercise performance and breathlessness.METHODS: Patients with COVID-19 were enrolled at the University Hospitals of Umeå and Örebro, and Karlstad Central Hospital, Sweden. Disease severity was defined as mild (nonhospitalized), moderate (hospitalized with or without oxygen treatment), and severe (intensive care). Spirometry, including diffusion capacity (DLCO ), was performed 3-6 months after hospital discharge or study enrollment (for nonhospitalized patients). Breathlessness (defined as ≥1 according to the modified Medical Research Council scale) and functional exercise capacity (1-min sit-to-stand test; 1-MSTST) were assessed.RESULTS: Between April 2020 and May 2021, 337 patients were enrolled in the study. Forced vital capacity and DLCO were significantly lower in patients with severe COVID-19. Among hospitalized patients, 20% had reduced DLCO , versus 4% in nonhospitalized. Breathlessness was found in 40.6% of the participants and was associated with impaired DLCO . A pathological desaturation or heart rate response was observed in 17% of participants during the 1-MSTST. However, this response was not associated with reduced DLCO .CONCLUSION: Reduced DLCO was the major respiratory impairment 3-6 months following COVID-19, with hospitalization as the most important risk factor. The lack of association between impaired DLCO and pathological physiological responses to exertion suggests that these physiological responses are not primarily related to decreased lung function.
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| 6. |
- Cagigi, Alberto, et al.
(author)
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Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
- 2021
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In: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:22
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Journal article (peer-reviewed)abstract
- Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.
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| 7. |
- Carrasco, Anna, et al.
(author)
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The Tonsil Lymphocyte Landscape in Pediatric Tonsil Hyperplasia and Obstructive Sleep Apnea
- 2021
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Journal article (peer-reviewed)abstract
- Tonsil hyperplasia is the most common cause of pediatric obstructive sleep apnea (OSA). Despite the growing knowledge in tissue immunology of tonsils, the immunopathology driving tonsil hyperplasia and OSA remains unknown. Here we used multi-parametric flow cytometry to analyze the composition and phenotype of tonsillar innate lymphoid cells (ILCs), T cells, and B cells from pediatric patients with OSA, who had previous polysomnography. Unbiased clustering analysis was used to delineate and compare lymphocyte heterogeneity between two patient groups: children with small tonsils and moderate OSA (n = 6) or large tonsils and very severe OSA (n = 13). We detected disturbed ILC and B cell proportions in patients with large tonsils, characterized by an increase in the frequency of naive CD27(-)CD21(hi) B cells and a relative reduction of ILCs. The enrichment of naive B cells was not commensurate with elevated Ki67 expression, suggesting defective differentiation and/or migration rather than cellular proliferation to be the causative mechanism. Finally, yet importantly, we provide the flow cytometry data to be used as a resource for additional translational studies aimed at investigating the immunological mechanisms of pediatric tonsil hyperplasia and OSA.
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| 8. |
- Dernstedt, Andy, et al.
(author)
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Regulation of Decay Accelerating Factor Primes Human Germinal Center B Cells for Phagocytosis
- 2021
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 11
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Journal article (peer-reviewed)abstract
- Germinal centers (GC) are sites for extensive B cell proliferation and homeostasis is maintained by programmed cell death. The complement regulatory protein Decay Accelerating Factor (DAF) blocks complement deposition on host cells and therefore also phagocytosis of cells. Here, we show that B cells downregulate DAF upon BCR engagement and that T cell-dependent stimuli preferentially led to activation of DAF(lo) B cells. Consistent with this, a majority of light and dark zone GC B cells were DAF(lo) and susceptible to complement-dependent phagocytosis, as compared with DAF(hi) GC B cells. We could also show that the DAF(hi) GC B cell subset had increased expression of the plasma cell marker Blimp-1. DAF expression was also modulated during B cell hematopoiesis in the human bone marrow. Collectively, our results reveal a novel role of DAF to pre-prime activated human B cells for phagocytosis prior to apoptosis.
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| 9. |
- Forsell, Eskil, et al.
(author)
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Predicting replication outcomes in the Many Labs 2 study
- 2019
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In: Journal of Economic Psychology. - : Elsevier. - 1872-7719 .- 0167-4870. ; 75:Part A SI
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Journal article (peer-reviewed)abstract
- Understanding and improving reproducibility is crucial for scientific progress. Prediction markets and related methods of eliciting peer beliefs are promising tools to predict replication outcomes. We invited researchers in the field of psychology to judge the replicability of 24 studies replicated in the large scale Many Labs 2 project. We elicited peer beliefs in prediction markets and surveys about two replication success metrics: the probability that the replication yields a statistically significant effect in the original direction (p < 0.001), and the relative effect size of the replication. The prediction markets correctly predicted 75% of the replication outcomes, and were highly correlated with the replication outcomes. Survey beliefs were also significantly correlated with replication outcomes, but had larger prediction errors. The prediction markets for relative effect sizes attracted little trading and thus did not work well. The survey beliefs about relative effect sizes performed better and were significantly correlated with observed relative effect sizes. The results suggest that replication outcomes can be predicted and that the elicitation of peer beliefs can increase our knowledge about scientific reproducibility and the dynamics of hypothesis testing.
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| 10. |
- Forsell, Johan, 1980-
(author)
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Assessment of abilities and knowledge learned in group
- 2017
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In: 18th Biennial Conference on Teachers and Teaching. - 9788469744185
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Conference paper (peer-reviewed)abstract
- Working cooperatively in groups is proven by numerous of studies to have positive effects on students learning. Researchers also describe how learning in groups comes with certain challenges and dilemmas.Teachers find it challenging to assess abilities and knowledge learned within a group. Students’, on the other hand, may consider unfairness as a problem when teachers assess individual abilities and knowledge based on the whole group. This ongoing research projects aim is to investigate how a short educational intervention can influence teachers´ understanding of assessment of abilities and knowledge learned in groups and how to develop new strategies to cope differently with the problems and dilemmas tied to the subject.The study is carried out in Swedish upper secondary high schools (students 15-18 years). The research includes six teachers who realize the same group task in their classes. Three of the teachers will function as a control group and get the intervention after the group project is carried out. The main content of the educational intervention is theories of how to assess abilities and knowledge learned in groups.Data is collected by individual interviews with the teachers and group interviews with students before and after the intervention and group project are carried out. Data will also be collected by video observation during the group project. This study will contribute with new important insights and knowledge of how teachers assess abilities and knowledge learned in groups and how they can develop strategies to cope with the challenges that comes with that.
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