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Background and purpose: During acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry. Methods: We analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression. Results: A total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20–1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07–1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19. Conclusion: Our data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection.
Menschen mit Behinderung haben dieselben Menschenrechte wie alle anderen Menschen: eigentlich eine Selbstverständlichkeit. Zur Bekräftigung und Präzisierung dieser Tatsache haben die Vereinten Nationen (UN) 2006 die Behindertenrechtskonvention verabschiedet, die von 158 Staaten unterzeichnet wurde – 2009 auch von der Bundesrepublik Deutschland. Darin werden auch spezifische, vor allem behinderte Menschen betreffende Regelungen getroffen. Artikel 24 bezieht sich auf den Bereich Bildung: Um Diskriminierung zu vermeiden und Chancengleichheit zu verwirklichen, verpflichten sich die Vertragsstaaten, ein integratives bzw. inklusives Schulsystem einzurichten. Dabei liegt der Fokus nicht an der Behinderung an sich, sondern auf den Barrieren, die die soziale Teilhabe einschränken. Ziel ist eine Gesellschaft, in der niemand integriert werden muss, weil jeder von vornherein dazugehört. Eine Utopie? Auf alle Fälle ein großes Ziel, an dem stetig und auf vielen Ebenen gearbeitet werden muss. In Deutschland wird über das Thema lebhaft diskutiert. Das deutsche Schulsystem mit seiner frühen Aufteilung der Kinder auf verschiedene Schulformen tut sich teils schwer mit der Umsetzung der Konvention. Diese verbietet Förderschulen zwar keineswegs, sie schreibt jedoch einen gleichberechtigten Zugang aller zum Bildungswesen vor. Ein Rückbau der Förderschulen würde den inklusiven Prozess beschleunigen und mehr Mittel freisetzen, argumentieren Experten. Auch die Stadt Frankfurt hat sich auf den Weg gemacht: Im Rahmen des Programms „Modellregion Inklusion“ sollen Förderschulen in Förderzentren umgebaut und Ressourcen an die Regelschulen verlagert werden. Auf Einladung des UniReports diskutieren der Frankfurter Erziehungswissenschaftler Prof. Dieter Katzenbach und Martina Franke, Leiterin der Johann-Hinrich-Wichern-Schule (Frankfurt) mit Förderschwerpunkt Lernen.
Abstract
The co-occurrence of insulin resistance (IR)-related metabolic conditions with neuropsychiatric disorders is a complex public health challenge. Evidence of the genetic links between these phenotypes is emerging, but little is currently known about the genomic regions and biological functions that are involved. To address this, we performed Local Analysis of [co]Variant Association (LAVA) using large-scale (N=9,725-933,970) genome-wide association studies (GWASs) results for three IR-related conditions (type 2 diabetes mellitus, obesity, and metabolic syndrome) and nine neuropsychiatric disorders. Subsequently, positional and expression quantitative trait locus (eQTL)-based gene mapping and downstream functional genomic analyses were performed on the significant loci. Patterns of negative and positive local genetic correlations (|rg|=0.21-1, pFDR<0.05) were identified at 109 unique genomic regions across all phenotype pairs. Local correlations emerged even in the absence of global genetic correlations between IR-related conditions and Alzheimer’s disease, bipolar disorder, and Tourette’s syndrome. Genes mapped to the correlated regions showed enrichment in biological pathways integral to immune-inflammatory function, vesicle trafficking, insulin signalling, oxygen transport, and lipid metabolism. Colocalisation analyses further prioritised 10 genetically correlated regions for likely harbouring shared causal variants, displaying high deleterious or regulatory potential. These variants were found within or in close proximity to genes, such as SLC39A8 and HLA-DRB1, that can be targeted by supplements and already known drugs, including omega-3/6 fatty acids, immunomodulatory, antihypertensive, and cholesterol-lowering drugs. Overall, our findings underscore the complex genetic landscape of IR-neuropsychiatric multimorbidity, advocating for an integrated disease model and offering novel insights for research and treatment strategies in this domain.
Highlights
Local genetic correlations found even in the absence of global correlations.
Both positive and negative local correlations found for IR-neuropsychiatric pairs.
Enrichment for immune, and insulin signalling pathways, among others.
Pinpointed shared likely causal variants within 10 genomic regions.
Identified therapeutic targets, e.g., SLC39A8 and HLA-DRB1, for drug repurposing.