SARS-CoV-2 vaccination and multiple sclerosis: a large multicentric study on relapse risk after the third booster dose

Background: COVID-19 vaccines have been recommended to people with multiple sclerosis (pwMS) and, to ensure durable immunity, a third booster dose has been administered in several countries. Data about potential risks associated with the third booster dose in pwMS, such as vaccine-triggered disease exacerbations, are still scarce. Objective: To investigate whether the administration of a third booster dose of mRNA COVID-19 vaccines was associated with an increased risk of short-term disease reactivation in a large cohort of pwMS. Methods: We retrospectively selected 1265 pwMS who received a third booster dose of an mRNA COVID-19 vaccine. Demographic and clinical data were collected, including the presence, number and characteristics of relapses in the 60 days prior to and after the third booster dose. Results: In the selected cohort, the relapse rate in the two months after administration of the third booster dose of mRNA COVID-19 vaccines did not increase when compared with the prior two months. Indeed, the percentage of pwMS experiencing relapses in the 60 days following the administration of the third booster dose was 2.1%, similar to the percentage recorded in 60 days prior to vaccination, which was 1.9%. Conclusions: The third booster dose of mRNA COVID-19 vaccines appeared to be safe for pwMS

Overexpression of the Cytokine BAFF and Autoimmunity Risk

$\textbf{BACKGROUND}$: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. $\textbf{METHODS}$: Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. $\textbf{RESULTS}$: A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. $\textbf{CONCLUSIONS}$: A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).Supported by grants (2011/R/13 and 2015/R/09, to Dr. Cucca) from the Italian Foundation for Multiple Sclerosis; contracts (N01-AG-1-2109 and HHSN271201100005C, to Dr. Cucca) from the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH); a grant (FaReBio2011 “Farmaci e Reti Biotecnologiche di Qualità,” to Dr. Cucca) from the Italian Ministry of Economy and Finance; a grant (633964, to Dr. Cucca) from the Horizon 2020 Research and Innovation Program of the European Union; a grant (U1301.2015/AI.1157.BE Prat. 2015-1651, to Dr. Cucca) from Fondazione di Sardegna; grants (“Centro per la ricerca di nuovi farmaci per malattie rare, trascurate e della povertà” and “Progetto collezione di composti chimici ed attività di screening,” to Dr. Cucca) from Ministero dell’Istruzione, dell’Università e della Ricerca; grants (HG005581, HG005552, HG006513, and HG007022, to Dr. Abecasis) from the National Human Genome Research Institute; a grant (9-2011-253, to Dr. Todd) from JDRF; a grant (091157, to Dr. Todd) from the Wellcome Trust; a grant (to Dr. Todd) from the National Institute for Health Research (NIHR); and the NIHR Cambridge Biomedical Research Centre. Dr. Idda was a recipient of a Master and Back fellowship from the Autonomous Region of Sardinia

Bespace: The community for space enthusiasts in Belgium

beSPACE, the community for space enthusiasts in Belgium, is a Belgian volunteer-based non-profit organisation founded in 2013 by a group of students and young professionals aiming to connect students and (young) professionals involved in space-related activities and help them with their education, training and career. It organised its first networking event, the Space Dinner, that same year. Since then the number of members has increased significantly, currently reaching 326, while the variety of events has expanded as well - from the Space Dinner, oriented towards the general public, with 270 registrations to company visits and smaller Sessions on specific topics for 15 people. In 2017 beSPACE introduced the beSPACE Awards to recognize and reward one individual (Personality of the Year) and one team (Team of the Year) that have made exceptional contributions to the (Belgian) space scene. The beSPACE core team consists of volunteers from many different backgrounds. The communication strategy is based on social media, a newsletter and a website. beSPACE published a White Paper in 2016, in which the core team outlines four recommendations in order for Belgium to remain a competitive European partner. These recommendations are: the creation of opportunities for the young generation, the inclusion of new trends in the national space strategy, the encouragement of transdisciplinary dialogue and opening up to the Belgian regions and communities while keeping the federal core. After five and a half years the number of participants of events has grown from 164 in 2013 to 339 in 2017. Social media have become more and more important, which is reflected in the number of followers on Facebook, Twitter and LinkedIn. Based on an analysis of the audience of a typical Space Dinner, beSPACE reaches its target audience of students, academics, professionals and other space enthusiasts. The lessons learnt are that more varied events increase visibility and attract a larger audience, that a clear sponsorship strategy attracts more sponsors and that social media are critical to communicate with members and other space enthusiasts. beSPACE now aims to organise its 7th Space Dinner, consolidate its digital identity, empower its members and keep growing its membership through the organisation of events where communication between space enthusiasts in Belgium is encouraged.SCOPUS: cp.pinfo:eu-repo/semantics/publishe

Characteristics and treatment of Multiple Sclerosis-related trigeminal neuralgia: an Italian multi-centre study

BACKGROUND: The prevalence of trigeminal neuralgia (TN) in Multiple Sclerosis (MS) patients is higher than in the general population and its management can be particularly challenging. Our aim is to describe the characteristics, treatment and prognostic factors of MS-related TN in a retrospective multicentre study. METHODS: Neurologists members of the RIREMS group (Rising Researchers in MS) enrolled MS patients with a TN diagnosis and filled out a spreadsheet comprising their clinical data. RESULTS: Population consisted of 298 patients. First-choice preventive treatments were carbamazepine and oxcarbazepine. A surgical procedure was performed in 81 (30%) patients, most commonly gamma knife stereotactic radiosurgery (37%), followed by microvascular decompression (22%) and radiofrequency thermocoagulation (21%); one third of patients underwent at least two procedures. Surgery was associated with higher disability, male sex and longer interval between MS and TN onset. Patients (77%) who stayed on at least one preventive medication at most recent follow-up, after a mean period of 8 years, had a higher disability compared to the untreated group. Furthermore, patients with higher disability at TN onset were less likely to discontinue their first preventive medication due to pain remission, had bilateral TN more frequently and underwent surgical interventions earlier. CONCLUSION: MS patients with a higher disability at TN onset and with a longer interval between MS and TN onset had differing clinical features and outcomes: pain was more frequently bilateral, surgery was more frequent and anticipated, and preventive medication discontinuation due to pain remission was less common

mRNA COVID-19 vaccines do not increase the short-term risk of clinical relapses in multiple sclerosis

[no abstract available

Overexpression of the cytokine BAFF and autoimmunity risk

BACKGROUND: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. METHODS: Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. RESULTS: A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. CONCLUSIONS: A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.)

Signs and symptoms of COVID-19 in patients with multiple sclerosis

Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation

The impact of PM2.5, PM10 and NO2 on Covid-19 severity in a sample of patients with multiple sclerosis: A case-control study

Background Many studies investigated the association between air pollution and Covid-19 severity but the only study focusing on patients with Multiple Sclerosis (MS) exclusively evaluated exposure to PM2.5. We aim to study, in a sample of MS patients, the impact of long-term exposure to PM2.5, PM10 and NO2 on Covid-19 severity, described as occurrence of pneumonia. Methods A 1:2 ratio case-control study was designed, differentiating cases and controls based on Covid-19 pneumonia. Associations between pollutants and outcome were studied using logistic regression. Weighted quantile sum (WQS) logistic regression was used to identify the individual contribution of each pollutant within the mixture; Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression was performed to confirm the variable selection from WQS. All the analyses were adjusted for confounders selected a priori. Results Of the 615 eligible patients, 491 patients provided detailed place of exposure and were included in the principal analysis. Higher concentrations of air pollutants were associated with increased odds of developing Covid-19 pneumonia (PM2.5: 3rd vs 1st tercile OR(95% CI)=2.26(1.29;3.96); PM10: 3rd vs 1st tercile OR(95% CI)=2.12(1.22;3.68); NO2: 3rd vs 1st tercile OR(95% CI)=2.12(1.21;3.69)). Pollutants were highly correlated with each other; WQS index was associated to an increased risk of pneumonia (β=0.44; p-value=0.004) and the main contributors to this association were NO2 (41%) and PM2.5 (34%). Consistently, Lasso method selected PM2.5 and NO2. Conclusions Higher long-term exposure to PM2.5, PM10 and NO2 increased the odds of Covid-19 pneumonia among MS patients and the most dangerous pollutants were NO2 and PM2.5