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Multiple Sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, causing increased vulnerability to infections and disability among young adults. Ever since the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 infections, there have been concerns among people with MS (PwMS) about the potential interactions between various disease-modifying therapies and COVID-19. The COVID-19 in MS Global Data Sharing Initiative (GDSI) was initiated in 2020 with the aim of addressing these concerns. This paper focuses on the anonymisation and publicly releasing of a GDSI sub-dataset, comprising data entered by PwMS and clinicians using a fast data entry tool. The dataset includes information on demographics, comorbidities and hospital stay and COVID-19 symptoms of PwMS. The dataset can be used to perform different statistical analyses to improve our understanding of COVID-19 in MS. Furthermore, this dataset can also be used within the context of educational activities to educate different stakeholders on the complex data science topics that were used within the GDSI.

Investigating low-prevalence diseases such as multiple sclerosis is challenging because of the rather small number of individuals affected by this disease and the scattering of real-world data across numerous data sources. These obstacles impair data integration, standardization, and analysis, which negatively impact the generation of significant meaningful clinical evidence. This study aims to present a comprehensive, research question-agnostic, multistakeholder-driven end-to-end data analysis pipeline that accommodates 3 prevalent data-sharing streams: individual data sharing, core data set sharing, and federated model sharing. A demand-driven methodology is employed for standardization, followed by 3 streams of data acquisition, a data quality enhancement process, a data integration procedure, and a concluding analysis stage to fulfill real-world data-sharing requirements. This pipeline's effectiveness was demonstrated through its successful implementation in the COVID-19 and multiple sclerosis global data sharing initiative. The global data sharing initiative yielded multiple scientific publications and provided extensive worldwide guidance for the community with multiple sclerosis. The pipeline facilitated gathering pertinent data from various sources, accommodating distinct sharing streams and assimilating them into a unified data set for subsequent statistical analysis or secure data examination. This pipeline contributed to the assembly of the largest data set of people with multiple sclerosis infected with COVID-19. The proposed data analysis pipeline exemplifies the potential of global stakeholder collaboration and underlines the significance of evidence-based decision-making. It serves as a paradigm for how data sharing initiatives can propel advancements in health care, emphasizing its adaptability and capacity to address diverse research inquiries.

Previous studies, predominantly based on increased or decreased plasma levels, have reported conflicting data on a potential functional role of ADAMTS13 in the pathogenesis of liver diseases, including non-alcoholic steatohepatitis (NASH). The aim of the current study was to evaluate whether ADAMTS13 deficiency affects development of NASH. Therefore, male wild-type (WT) and Adamts13 deficient (Adamts13−/−) mice were kept on a steatosis-inducing diet devoid of methionine and choline (MCD) or a control diet (MCC) for 4 weeks. Induction of NASH did not affect plasma ADAMTS13 antigen levels of WT mice. MCD as compared with MCC feeding resulted in reduced body and liver weight with no differences between the genotypes. Plasma levels of the liver enzymes AST and ALT were significantly higher for MCD vs. MCC fed Adamts13−/− and WT mice, however were not different between the genotypes. Liver triglyceride levels were also higher after MCD feeding, but were not different between WT and Adamts13−/− mice. Adamts13−/− mice on the two diets exhibited higher insulin sensitivity when compared with WT mice. On the MCC diet, the genotype did not show clear histological abnormalities in the liver, whereas severe steatosis and fibrosis were observed on MCD diet, however were comparable for both genotypes. This was supported by comparably enhanced hepatic expression in the two genotypes on MCD diet of the steatosis marker CD36 and of the fibrosis marker tissue inhibitor of metalloproteinase 1. Thus, the results of the current study do not support a functional role of ADAMTS13 in this murine model of NASH.

ObjectivesSome disease-modifying therapies (DMTs) have been associated with COVID-19 severity in people with MS. Comprehensive exploration of these relationships in large international samples is needed.MethodsClinician-reported demographic/clinical data from 27 countries were aggregated into a dataset of 5,648 patients with suspected/confirmed COVID-19. COVID-19 severity outcomes (hospitalisation, admission to ICU, requiring artificial ventilation, death) assessed using multilevel mixed-effect ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were compared to glatiramer acetate, dimethyl fumarate, pooled other DMTs, and natalizumab.ResultsOf 5,648 patients (83.4% confirmed COVID-19) were included. Compared to glatiramer acetate, ocrelizumab and rituximab were associated with higher probability of hospitalisation (4%(95%CI=1–7) & 7%(95%CI=4–11)), ICU/artificial ventilation (2%(95%CI=0–4) & 4%(95%CI=2–6)), and death (1%(95%CI=0–2) & 2%(95%CI=1–4)) [predicted marginal effects]. Untreated patients had 5%(95%CI=2–8), 3%(95%CI=1–5), and 1%(95%CI=0–3) higher probabilities of the three respective levels of COVID-19 severity than glatiramer acetate. Compared to pooled other DMTs and to natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. Evaluation of interferon associations with COVID-19 severity found these only apparent in comparison with the untreated but not vs individual or pooled other DMTs. All associations persisted/enhanced on restriction to confirmed COVID-19.ConclusionsAnalysing the largest international real-world dataset of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab) are associated with more severe course of COVID-19, while interferon-based DMTs have no intrinsic protective benefit from other treatment.