| 1. |
- Gröning, Remigius, et al.
(författare)
-
Intravenous immunoglobulin therapy for COVID-19 in immunocompromised patients : A retrospective cohort study
- 2024
-
Ingår i: International Journal of Infectious Diseases. - : Elsevier. - 1201-9712 .- 1878-3511. ; 144
-
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.
|
|
| 2. |
- Orikiiriza, Judy, et al.
(författare)
-
Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria
- 2017
-
Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 13:4
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Several studies have observed serum lipid changes during malaria infection in humans. All of them were focused at analysis of lipoproteins, not specific lipid molecules. The aim of our study was to identify novel patterns of lipid species in malaria infected patients using lipidomics profiling, to enhance diagnosis of malaria and to evaluate biochemical pathways activated during parasite infection.Methods: Using a multivariate characterization approach, 60 samples were representatively selected, 20 from each category (mild, severe and controls) of the 690 study participants between age of 0.5–6 years. Lipids from patient’s plasma were extracted with chloroform/methanol mixture and subjected to lipid profiling with application of the LCMS-QTOF method.Results: We observed a structured plasma lipid response among the malaria-infected patients as compared to healthy controls, demonstrated by higher levels of a majority of plasma lipids with the exception of even-chain length lysophosphatidylcholines and triglycerides with lower mass and higher saturation of the fatty acid chains. An inverse lipid profile relationship was observed when plasma lipids were correlated to parasitaemia.Conclusions: This study demonstrates how mapping the full physiological lipid response in plasma from malaria-infected individuals can be used to understand biochemical processes during infection. It also gives insights to how the levels of these molecules relate to acute immune responses.
|
|
| 3. |
- Surowiec, Izabella, et al.
(författare)
-
Joint and unique multiblock analysis of biological data : multiomics malaria study
- 2019
-
Ingår i: Faraday discussions. - Cambridge : Royal Society of Chemistry. - 1359-6640 .- 1364-5498. ; 218, s. 268-283
-
Tidskriftsartikel (refereegranskat)abstract
- Modern profiling technologies enable obtaining large amounts of data which can be later used for comprehensive understanding of the studied system. Proper evaluation of such data is challenging, and cannot be faced by bare analysis of separate datasets. Integrated approaches are necessary, because only data integration allows finding correlation trends common for all studied data sets and revealing hidden structures not known a priori. This improves understanding and interpretation of the complex systems. Joint and Unique MultiBlock Analysis (JUMBA) is an analysis method based on the OnPLS-algorithm that decomposes a set of matrices into joint parts containing variation shared with other connected matrices and variation that is unique for each single matrix. Mapping unique variation is important from a data integration perspective, since it certainly cannot be expected that all variation co-varies. In this work we used JUMBA for integrated analysis of lipidomic, metabolomic and oxylipin datasets obtained from profiling of plasma samples from children infected with P. falciparum malaria. P. falciparum is one of the primary contributors to childhood mortality and obstetric complications in the developing world, what makes development of the new diagnostic and prognostic tools, as well as better understanding of the disease, of utmost importance. In presented work JUMBA made it possible to detect already known trends related to disease progression, but also to discover new structures in the data connected to food intake and personal differences in metabolism. By separating the variation in each data set into joint and unique, JUMBA reduced complexity of the analysis, facilitated detection of samples and variables corresponding to specific structures across multiple datasets and by doing this enabled fast interpretation of the studied system. All this makes JUMBA a perfect choice for multiblock analysis of systems biology data.
|
|
| 4. |
- Surowiec, Izabella, et al.
(författare)
-
Metabolic signature profiling as a diagnostic and prognostic tool in paediatric Plasmodium falciparum malaria
- 2015
-
Ingår i: Open Forum Infectious Diseases. - : Oxford University Press. - 2328-8957. ; 2:2
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Accuracy in malaria diagnosis and staging is vital in order to reduce mortality and post infectious sequelae. Herein we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children. Methods: A group of 421 patients between six months and six years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192 and 122 individuals respectively. A multivariate design was used as basis for representative selection of twenty patients in each category. Patient plasma was subjected to Gas Chromatography-Mass Spectrometry analysis and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in-vivo model where metabolic profiles were discernible over time of infection. Results: A two-component principal component analysis (PCA) revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, two sub-groups could be identified in the mild malaria cohort who we believe represent patients with divergent prognoses. Conclusion: Metabolite signature profiling could be used both for decision support in disease staging and prognostication.
|
|
| 5. |
- Surowiec, Izabella, et al.
(författare)
-
Quantification of run order effect on chromatography : mass spectrometry profiling data
- 2018
-
Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1568, s. 229-234
-
Tidskriftsartikel (refereegranskat)abstract
- Chromatographic systems coupled with mass spectrometry detection are widely used in biological studies investigating how levels of biomolecules respond to different internal and external stimuli. Such changes are normally expected to be of low magnitude and therefore all experimental factors that can influence the analysis need to be understood and minimized. Run order effect is commonly observed and constitutes a major challenge in chromatography-mass spectrometry based profiling studies that needs to be addressed before the biological evaluation of measured data is made. So far there is no established consensus, metric or method that quickly estimates the size of this effect. In this paper we demonstrate how orthogonal projections to latent structures (OPLS®) can be used for objective quantification of the run order effect in profiling studies. The quantification metric is expressed as the amount of variation in the experimental data that is correlated to the run order. One of the primary advantages with this approach is that it provides a fast way of quantifying run-order effect for all detected features, not only internal standards. Results obtained from quantification of run order effect as provided by the OPLS can be used in the evaluation of data normalization, support the optimization of analytical protocols and identification of compounds highly influenced by instrumental drift. The application of OPLS for quantification of run order is demonstrated on experimental data from plasma profiling performed on three analytical platforms: GCMS metabolomics, LCMS metabolomics and LCMS lipidomics.
|
|
| 6. |
- Surowiec, Izabella, et al.
(författare)
-
The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children
- 2017
-
Ingår i: Malaria Journal. - : BIOMED CENTRAL LTD. - 1475-2875 .- 1475-2875. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism.Methods: Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA (R)) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis).Results: Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls.Conclusions: It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed.
|
|
| 7. |
- Ahmad, Irma, et al.
(författare)
-
High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19
- 2023
-
Ingår i: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 11
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 8. |
- Albrecht, Letusa, et al.
(författare)
-
var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2
- 2011
-
Ingår i: Malaria Journal. - : BioMed Central. - 1475-2875 .- 1475-2875. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra- vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of approximate to 60 var genes. Methods: The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence. Results: Transcripts from var1 (FCR3S1.2(var1); IT4var21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2var2; IT4var60). Antibodies raised in rats to the recombinant NTS-DBL1a of var2 produced in E. coli completely and dosedependently disrupted rosettes (approximate to 95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2var2 encodes the dominant PfEMP1 expressed in this parasite. Conclusion: The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2var2 (IT4var60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1a of FCR3S1.2var1 is likely due to cross-reactivity with NTS-DBL1 alpha of the var2 encoded PfEMP1.
|
|
| 9. |
- Bergström, Sven, et al.
(författare)
-
Microbiological features distinguishing Lyme disease and relapsing fever spirochetes
- 2018
-
Ingår i: Wiener Klinische Wochenschrift. - : Springer. - 0043-5325 .- 1613-7671. ; 130:15-16, s. 484-490
-
Tidskriftsartikel (refereegranskat)abstract
- The recent proposal of splitting the genus Borrelia into two genera in the newly formed family of Borreliaceae, i.aEuroe. Borrelia and Borreliella has motivated us to reflect upon how these organisms has been characterized and differentiated. This article therefore aims to take a closer look on the biology and virulence attributes of the two suggested genera, i.aEuroe. those causing Lyme borreliosis and relapsing fever borreliosis. Both genera have much in common with similar infection biological features. They are both characterized as bacterial zoonoses, transmitted by hematophagous arthropods with almost identical microbiological appearance. Nevertheless, a closer look at the genotypic and phenotypic characteristics clearly reveals several differences that might motivate the suggested split. On the other hand, a change of this well-established classification within the genus Borrelia might impose an economical burden as well as a great confusion in society, including medical and scientific societies as well as the general population.
|
|
| 10. |
|
|
