Iskanje po repozitoriju

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Povzetek: Background Paediatric patients with autoimmune rheumatic diseases (pARD) have a dysregulated immune system, so infections present a major threat to them. To prevent severe COVID-19 infections we aimed to vaccinate them as soon as possible. Studies have shown that the BNT162b2 vaccine is safe, effective, and immunogenic, however, in a short observation period, only. Methods The main objective was to compare the serological response between three groups of pARD: after SARSCoV-2 infection, after vaccination against COVID-19 with two doses of the BNT162b2 vaccine, and after experiencing both events. Data on demographics, diagnosis, therapy, and serology (anti-SARS-CoV-2 IgG/IgA) were collected from March 2020 to April 2022. For statistical analysis ANOVA, Mann-Whitney U test, Chi-square test and Fisher’s exact test were applied. To compare adverse events (AE) after vaccination we included a control group of healthy adolescents. Results We collected data from 115 pARD; from 92 after infection and 47 after vaccination. Twenty-four were included in both groups. Serological data were available for 47 pARD after infection, 25 after vaccination, and 21 after both events. Serological response was better after vaccination and after both events compared to after infection only. No effect of medication on the antibody levels was noted. The safety profile of the vaccine was good. Systemic AE after the first dose of the vaccine were more common in healthy adolescents compared to pARD. In the observation period of 41.3 weeks, 60% of vaccinated pARD did not experience a symptomatic COVID-19 infection. Conclusions IgG and IgA anti-SARS-CoV-2 levels were higher after vaccination and after both events compared to after infection only. Six months after vaccination we observed an increase in antibody levels, suggesting that pARD had been exposed to SARS-CoV-2 but remained asymptomatic.
Ključne besede: covid-19, vaccination, efficacy, paediatric autoimmune rheumatic diseases
Objavljeno v DiRROS: 16.06.2026; Ogledov: 45; Prenosov: 30
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Povzetek: Background The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fngolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset. Methods A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defned: pre-pandemic (March 11 2018–March 10 2020) and post-pandemic onset (March 11 2020–11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-efects logistic regression. DMT initiation refers to frst initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use. Results Post-pandemic onset, there was a signifcant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39–2.13; switching: OR 1.66, 95% CI 1.40–1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09–1.87; switching: OR 1.67, 95% CI 1.41–1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06–1.49; Switching: OR 1.15, 95% CI 1.02–1.29. Initiation/switching of fngolimod, interferon-beta, and alemtuzumab signifcantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41–0.73; switching: OR 0.49, 95% CI 0.41–0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41–0.57; switching: OR 0.78, 95% CI 0.62–0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15–0.48; switching: OR 0.27, 95% CI 0.17–0.44)]. Conclusions Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fngolimod, likely to preserve efcacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our fndings highlight the signifcance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges.
Ključne besede: multiple sclerosis, covid-19, disease-modifying therapy
Objavljeno v DiRROS: 12.06.2026; Ogledov: 67; Prenosov: 41
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Povzetek: Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population- dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained by combining an extensive review of the literature, target genes identified by the COVID-19 Host Genetic Initiative, and the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with a severe COVID-19 outcome.
Ključne besede: severe COVID-19, severe outcome of SARS-CoV-2 infection, whole-genome sequencing, genetic susceptibility, rare variants, human rare genomic variants
Objavljeno v DiRROS: 11.06.2026; Ogledov: 116; Prenosov: 81
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Povzetek: Introduction: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19. Genetic polymorphisms of the glucocorticoid receptor, metabolizing enzymes, or transporters may affect treatment response to dexamethasone. This study aimed to evaluate the association of the glucocorticoid pathway polymorphisms with the treatment response and short-term outcomes in patients with severe COVID-19. Methods: Our pilot study included 107 hospitalized patients with COVID-19 treated with dexamethasone and/or methylprednisolone, genotyped for 14 polymorphisms in the glucocorticoid pathway. Results: In total, 83% of patients had severe disease, 15.1% had critical disease and only 1.9% had moderate disease. CYP3A4 rs35599367 was the major genetic determinant of COVID-19 severity as carriers of this polymorphism had higher risk of critical disease (OR = 6.538; 95% confidence interval = 1.19-35.914: p = 0.031) and needed intensive care unit treatment more frequently (OR = 10; 95% CI = 1.754-57.021: p = 0.01). This polymorphism was also associated with worse disease outcomes, as those patients had to switch from dexamethasone to methylprednisolone more often (OR = 6.609; 95% CI = 1.137-38.424: p = 0.036), had longer hospitalization (p = 0.022) and needed longer oxygen supplementation (p = 0.040). Carriers of NR3C1 rs6198 polymorphic allele required shorter dexamethasone treatment (p = 0.043), but had higher odds for switching therapy with methylprednisolone (OR = 2.711; 95% CI = 1.018-7.22: p = 0.046). Furthermore, rs6198 was also associated with longer duration of hospitalization (p = 0.001) and longer oxygen supplementation (p = 0.001). NR3C1 rs33388 polymorphic allele was associated with shorter hospitalization (p = 0.025) and lower odds for ICU treatment (OR = 0.144; 95% CI = 0.027-0.769: p = 0.023). GSTP1 rs1695 was associated with duration of hospitalization (p = 0.015), oxygen supplementation and (p = 0.047) dexamethasone treatment (p = 0.022). Conclusion: Our pathway-based approach enabled us to identify novel candidate polymorphisms that can be used as predictive biomarkers associated with response to glucocorticoid treatment in COVID-19. This could contribute to the patient's stratification and personalized treatment approach.
Ključne besede: COVID-19, dexamethasone, glucocorticoid pathway, methylprednisolone, polymorphism, treatment outcome
Objavljeno v DiRROS: 08.06.2026; Ogledov: 154; Prenosov: 88
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Povzetek: We analyzed data from seven years, accounting for 441,149 patient days. The incidence density of multidrug-resistant bacteria (MDR) burden and infection was reported per 1000 patient days. Results. During COVID-19, a significant increase in the mean incidence density of the total MDR burden from 4.93 to 5.81 per 1000 patient days was observed (p = 0.007). On the other hand, the mean incidence density of MDR infections decreased from 1.61 to 1.29 per 1000 patient days (p = 0.019). Using the interrupted time series analysis, the same trends were observed, namely the overall increasing trend in MDR burden and the overall decreasing trend in MDR infections. This divergent trend is mainly due to similar trends in several Gram-negative MDR, namely ESBL-EC, ESBL-KP and CRE. Due to the increasing burden of MDR, it is necessary to strengthen AMR surveillance. In addition, strict infection prevention and control measures, and antimicrobial stewardship programs continue to be important.
Ključne besede: antimicrobial resistance, COVID-19, Slovenia, interrupted time series analysis
Objavljeno v DiRROS: 03.06.2026; Ogledov: 147; Prenosov: 88
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