Gaming for Social Inclusion and Civic Participation: the INGAME project

[EN] Throughout the European Union, there is a particular need for practices that would provide educators with the devices necessary to create civic engagement locally and supra-nationally responsive. The INGAME project focuses on enhancing the acquisition of social and civic competences, fostering knowledge, understanding and ownership of values and fundamental rights with a strong focus on online games and digital skills for the development of civic literacy and skills of young adults. It is placed under the Erasmus + KA3 Social inclusion and common values: the contribution in education and training

The predictive role of symptoms in COVID-19 diagnostic models : A longitudinal insight

Acknowledgements 2019nCoV-302 Study Group Members: The NVX-CoV2373-2019nCoV-302 clinical trial was a collective group effort across multiple institutions and locations. Below is a list of sites and staff that significantly contributed to the implementation and conduct of the NVX-CoV2373-2019nCoV-302 clinical trial.Peer reviewe

Safety and efficacy of the NVX-CoV2373 coronavirus disease 2019 vaccine at completion of the placebo-controlled phase of a randomized controlled trial

Background: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. Methods: Adults aged 18–84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. Results: Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%–88.8%). Vaccine efficacy was 100% (95% CI, 17.9%–100.0%) against severe disease and 76.3% (95% CI, 57.4%–86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein–specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. Conclusions: A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated. Clinical Trials Registration: EudraCT, 2020-004123-16

Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial

Acknowledgements The study and article were funded by Novavax. We would like to thank all the study participants for their commitment to this study. We also acknowledge the investigators and their study teams for their hard work and dedication. In addition, we would like to thank the National Institute for Health Research, representatives from the Department of Health and Social Care laboratories and NHS Digital and the members of the UK Vaccine Task Force. Editorial support was provided by Kelly Cameron of Ashfield MedComms, an Inizio company Funding This work was funded by Novavax, and the sponsor had primary responsibility for study design, study vaccines, protocol development, study monitoring, data management, and statistical analyses. All authors reviewed and approved the manuscript before submission. LF reports a position as a prior full-time employee, now contractor to Novavax re-imbursed hourly for work performed on this study and in analyses and drafting this report. IC reports providing medical writing support for this work as an employee of NovavaxPeer reviewedPublisher PD

Safety, immunogenicity, and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines: an exploratory substudy of a randomised, observer-blinded, placebo-controlled, phase 3 trial

Background: Safety and immunogenicity of COVID-19 vaccines when co-administered with influenza vaccines have not yet been reported. Methods: A sub-study on influenza vaccine co-administration was conducted as part of the phase 3 randomised trial of NVX-CoV2373’s safety and efficacy; ~400 participants meeting main study entry criteria, with no contraindications to influenza vaccination, were enroled. After randomisation to receive NVX-CoV2373 or placebo, sub-study participants received an open-label influenza vaccine at the same time as the first dose of NVX-CoV2373. Reactogenicity was evaluated for 7 days post-vaccination plus monitoring for unsolicited adverse events (AEs), medically-attended AEs (MAAEs), and serious AEs (SAEs). Vaccine efficacy against COVID-19 was assessed. Findings: Sub-study participants were younger (median age 39; 6.7 % ≥65 years), more racially diverse, and had fewer comorbid conditions than main study participants. Reactogenicity events more common in co-administration group included tenderness (70.1% vs 57.6%) or pain (39.7% vs 29.3%) at injection site, fatigue (27.7% vs 19.4%), and muscle pain (28.3% vs 21.4%). Rates of unsolicited AEs, MAAEs, and SAEs were low and balanced between the two groups. Co-administration resulted in no change to influenza vaccine immune response, while a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. Vaccine efficacy against COVID-19 was 87.5% (95% CI: -0.2, 98.4) in those 18-<65 years in the sub-study while efficacy in the main study was 89.8% (95% CI: 79.7, 95.5).  Interpretation: This is the first study to demonstrate safety, immunogenicity, and efficacy of a COVID-19 vaccine when co-administered with influenza vaccines

Safety and efficacy of the NVX-CoV2373 coronavirus disease 2019 vaccine at completion of the placebo-controlled phase of a randomized controlled trial

Background: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. Methods: Adults aged 18–84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. Results: Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%–88.8%). Vaccine efficacy was 100% (95% CI, 17.9%–100.0%) against severe disease and 76.3% (95% CI, 57.4%–86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein–specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. Conclusions: A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through &gt;6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Maternally Inherited Diabetes and Deafness (MIDD) – Atypical Clinical Diabetes Features Leading to the Diagnosis

Maternally inherited diabetes and deafness (MIDD) syndrome refers to a rarely diagnosed disorder caused by pathogenic variants in mtDNA. It was first identified in 1992 and, to date, is considered underdiagnosed because of misclassification to type 1 or type 2 diabetes mellitus. MIDD reflects a multisystem metabolic syndrome commonly resulting in insulin-requiring diabetes and sensorineural deafness but can also lead to a broad range of other manifestations. The spectrum of pathology differs among individuals, likely because of varied degrees of heteroplasmy associated with mtDNA. Heteroplasmy also creates diagnostic difficulties, with a high index of suspicion required to diagnose MIDD in some cases. Here, we review a patient with MIDD who presented with an atypical clinical diabetes picture, additionally documenting his pedigree. To our knowledge, this is the first Cypriot reported with MIDD

Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19.

Measuring immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), can rely on antibodies, reactive T cells and other factors, with T-cell-mediated responses appearing to have greater sensitivity and longevity. Because each T cell carries an essentially unique nucleic acid sequence for its T-cell receptor (TCR), we can interrogate sequence data derived from DNA or RNA to assess aspects of the immune response. This review deals with the utility of bulk, rather than single-cell, sequencing of TCR repertoires, considering the importance of study design, in terms of cohort selection, laboratory methods and analysis. The advances in understanding SARS-CoV-2 immunity that have resulted from bulk TCR repertoire sequencing are also be discussed. The complexity of sequencing data obtained by bulk repertoire sequencing makes analysis challenging, but simple descriptive analyses, clonal analysis, searches for specific sequences associated with immune responses to SARS-CoV-2, motif-based analyses, and machine learning approaches have all been applied. TCR repertoire sequencing has demonstrated early expansion followed by contraction of SARS-CoV-2-specific clonotypes, during active infection. Maintenance of TCR repertoire diversity, including the maintenance of diversity of anti-SARS-CoV-2 response, predicts a favourable outcome. TCR repertoire narrowing in severe COVID-19 is most likely a consequence of COVID-19-associated lymphopenia. It has been possible to follow clonotypic sequences longitudinally, which has been particularly valuable for clonotypes known to be associated with SARS-CoV-2 peptide/MHC tetramer binding or with SARS-CoV-2 peptide-induced cytokine responses. Closely related clonotypes to these previously identified sequences have been shown to respond with similar kinetics during infection. A possible superantigen-like effect of the SARS-CoV-2 spike protein has been identified, by means of observing V-segment skewing in patients with severe COVID-19, together with structural modelling. Such a superantigen-like activity, which is apparently absent from other coronaviruses, may be the basis of multisystem inflammatory syndrome and cytokine storms in COVID-19. Bulk TCR repertoire sequencing has proven to be a useful and cost-effective approach to understanding interactions between SARS-CoV-2 and the human host, with the potential to inform the design of therapeutics and vaccines, as well as to provide invaluable pathogenetic and epidemiological insights