Open Access of COVID-19-related publications in the first quarter of 2020: a preliminary study based in PubMed

Background: The COVID-19 outbreak has made funders, researchers and publishers agree to have research publications, as well as other research outputs, such as data, become openly available. In this extraordinary research context of the SARS CoV-2 pandemic, publishers are announcing that their coronavirus-related articles will be made immediately accessible in appropriate open repositories, like PubMed Central (PMC), agreeing upon funders' and researchers' instigation.Methods: This work uses Unpaywall, OpenRefine and PubMed to analyse the level of openness of the papers about COVID-19, published during the first quarter of 2020. It also analyses Open Access (OA) articles published about previous coronavirus (SARS CoV-1 and MERS CoV) as a means of comparison.Results: A total of 5,611 COVID-19-related articles were analysed from PubMed. This is a much higher amount for a period of 4 months compared to those found for SARS CoV-1 and MERS during the first year of their first outbreaks (337 and 125 articles, respectively). Regarding the levels of openness, 97.4% of the SARS CoV-2 papers are freely available; similar rates were found for the other coronaviruses. Deeper analysis showed that (i) 68.3% of articles belong to an undefined Bronze category; (ii) 72.1% of all OA papers don't carry a specific license and in all cases where there is, half of them do not meet Open Access standards; (iii) there is a large proportion that present a copy in a repository, in most cases in PMC, where this trend is also observed. These patterns were found to be repeated in most frequent publishers: Elsevier, Springer and Wiley.Conclusions: Our results suggest that, although scientific production is much higher than during previous epidemics and is open, there is a caveat to this opening, characterized by the absence of fundamental elements and values ​​on which Open Science is based, such as licensing[version 2; peer review: 2 approved, 1 approved with reservations

Genomic characterization of host factors related to SARS-CoV-2 infection in people with dementia and control populations: the GR@ACE/DEGESCO study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis

Long runs of homozygosity are associated with Alzheimer’s disease

Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a finescale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [βAVROH (CI 95%) = 0.070 (0.037–0.104); P = 3.91 × 10−5; βFROH (CI95%) = 0.043 (0.009–0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10−16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10−4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in wholeexome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability.Consejería de Salud de la Junta de Andalucía PI-0001/201

Development of an Interactive Lifestyle Programme for Adolescents at Risk of Developing Type 2 Diabetes: PRE-STARt

Background: Type 2 diabetes (T2D) is increasing in young people. Reporting on the processes used when developing prevention interventions is needed. We present the development of a family-based interactive lifestyle intervention for adolescents with risk factors for T2D in the future. Method: A multidisciplinary team in the UK site led the intervention development process with sites in Portugal, Greece, Germany and Spain. Potential programme topics and underpinning theory were gathered from literature and stakeholders. A theoretical framework based on self-efficacy theory and the COM-B (capability, opportunity, motivation, behaviour) model was developed. Sessions and supporting resources were developed and refined via two iterative cycles of session and resource piloting, feedback, reflection and refinement. Decision on delivery and content were made by stakeholders (young people, teachers, parents, paediatricians) and all sites. Materials were translated to local languages. Site-specific adaptations to the language, content and supporting resources were made. Results: The “PRE-STARt” programme is eight 90-min interactive sessions with supporting curriculum and resources. Iterative development work provided valuable feedback on programme content and delivery. Conclusion: Reporting on the intervention development process, which includes stakeholder input, could yield a flexible approach for use in this emerging ‘at risk’ groups and their families

Identification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect After a Drug Repurposing Screen

There is an urgent need to identify therapeutics for the treatment of Coronavirus disease 2019 (COVID-19). Although different antivirals are given for the clinical management of SARS-CoV-2 infection, their efficacy is still under evaluation. Here, we have screened existing drugs approved for human use in a variety of diseases, to compare how they counteract SARS-CoV-2-induced cytopathic effect and viral replication in vitro. Among the potential 72 antivirals tested herein that were previously proposed to inhibit SARS-CoV-2 infection, only 18 % had an IC50 below 25 µM or 102 IU/ml. These included plitidepsin, novel cathepsin inhibitors, nelfinavir mesylate hydrate, interferon 2-alpha, interferon-gamma, fenofibrate, camostat along the well-known remdesivir and chloroquine derivatives. Plitidepsin was the only clinically approved drug displaying nanomolar efficacy. Four of these families, including novel cathepsin inhibitors, blocked viral entry in a cell-type specific manner. Since the most effective antivirals usually combine therapies that tackle the virus at different steps of infection, we also assessed several drug combinations. Although no particular synergy was found, inhibitory combinations did not reduce their antiviral activity. Thus, these combinations could decrease the potential emergence of resistant viruses. Antivirals prioritized herein identify novel compounds and their mode of action, while independently replicating the activity of a reduced proportion of drugs which are mostly approved for clinical use. Combinations of these drugs should be tested in animal models to inform the design of fast track clinical trials.info:eu-repo/semantics/publishedVersio

Immune response and reactogenicity after immunization with two-doses of an experimental COVID-19 vaccine (CVnCOV) followed by a third-fourth shot with a standard mRNA vaccine (BNT162b2): RescueVacs multicenter cohort study

Background: There is no evidence to date on immunogenic response among individuals who participated in clinical trials of COVID-19 experimental vaccines redirected to standard national vaccination regimens. Methods: This multicentre, prospective controlled cohort study included subjects who received a COVID-19 experimental vaccine (CVnCoV)(test group, TG) - and unvaccinated subjects (control group, CG), selected among individuals to be vaccinated according to the Spanish vaccination program. All study subjects received BNT162b2 as a standard national vaccination schedule, except 8 (from CG) who received mRNA-1273 and were excluded from immunogenicity analyses. Anti-RBD antibodies level and neutralising titres (NT50) against G614, Beta, Mu, Delta and Omicron variants were analysed. Reactogenicity was also assessed. Findings: 130 participants (TG:92; CG:38) completed standard vaccination. In TG, median (IQR) of anti-RBD antibodies after first BNT162b2 dose were 10740·0 BAU/mL (4466·0-12500) compared to 29·8 BAU/mL (14·5-47·8) in CG (p <0·0001). Median NT50 (IQR) of G614 was 2674·0 (1865·0-3997·0) in TG and 63·0 (16·0-123·1) in CG (p <0·0001). After second BNT162b2 dose, anti-RBD levels increased to ≥12500 BAU/mL (11625·0-12500) in TG compared to 1859·0 BAU/mL (915·4-3820·0) in CG (p <0·0001). NT50 was 2626·5 (1756·0-5472·0) and 850·4 (525·1-1608·0), respectively (p <0·0001). Variant-specific (Beta, Mu, Omicron) response was also assessed. Most frequent adverse reactions were headache, myalgia, and local pain. No severe AEs were reported. Interpretation: Heterologous BNT162b2 as third and fourth doses in previously suboptimal immunized individuals elicit stronger immune response than that obtained with two doses of BNT162b2. This apparent benefit was also observed in variant-specific response. No safety concerns arose.This work is partially funded by Institute of Health Carlos III (Instituto de Salud Carlos III − ISCIII −), (grants PI19CIII/00004 −JA- and PI21CIII/00025 −MPO, JG-), and COVID-19 FUND (grants COV20/00679 −MPO- and COV20/00072 −JA-) and CIBERINFEC, co-financed by the European Regional Development Fund (FEDER) “A way to make Europe”. Instituto de Salud Carlos III is a Spanish public body assigned to the Ministry of Science and Innovation that manages and promotes public clinical research related to public health. The authors thank Esther Prieto, MD (cited with consent) for editorial assistance and writing support (funded by the Research Foundation of HCSC).S

UPRIGHT, a resilience-based intervention to promote mental well-being in schools: study rationale and methodology for a European randomized controlled trial

Background: Adolescence is crucial period for laying the foundations for healthy development and mental wellbeing. The increasing prevalence of mental disorders amongst adolescents makes promotion of mental well-being and prevention interventions at schools important. UPRIGHT (Universal Preventive Resilience Intervention Globally implemented in schools to improve and promote mental Health for Teenagers) is designed as a whole school approach (school community, students and families) to promote a culture of mental well-being and prevent mental disorders by enhancing resilience capacities. The present article aims at describing the rationale, conceptual framework, as well as methodology of implementation and evaluation of the UPRIGHT intervention.Methods: UPRIGHT project is a research and innovation project funded by the European Union's Horizon 2020 Research and Innovation programme under grant agreement No. 754919 (Duration: 48 months). The theoretical framework has been developed by an innovative and multidisciplinary approach using a co-creation process inside the UPRIGHT Consortium (involving seven institutions from Spain, Italy, Poland, Norway, Denmark, and Iceland). Resulted is the UPRIGHT programme with 18 skills related to 4 components: Mindfulness, Coping, Efficacy and Social and Emotional Learning. Among the five Pan-European regions, 34 schools have been currently involved (17 control; 17 intervention) and around 6000 adolescents and their families are foreseen to participate along a 3-year period of evaluation. Effectiveness of the intervention will be evaluated as a randomized controlled trial including quantitative and qualitative analysis in the five Pan-European regions representative of the cultural and socioeconomic diversity. The cost-effectiveness assessment will be performed by simulation modelling methods.Discussion: We expect a short- to medium-term improvement of mental well-being in adolescents by enhancing resilience capacities. The study may provide robust evidence on intrapersonal, familiar and social environmental resilience factors promoting positive mental well-being.Trial registration: ClinicalTrials.gov Identifier: NCT03951376. Registered 15 May 2019

Development of an interactive lifestyle programme for adolescents at risk of developing type 2 diabetes : PRE-STARt

Background: Type 2 diabetes (T2D) is increasing in young people. Reporting on the processes used when developing prevention interventions is needed. We present the development of a family-based interactive lifestyle intervention for adolescents with risk factors for T2D in the future. Method: A multidisciplinary team in the UK site led the intervention development process with sites in Portugal, Greece, Germany and Spain. Potential programme topics and underpinning theory were gathered from literature and stakeholders. A theoretical framework based on self-efficacy theory and the COM-B (capability, opportunity, motivation, behaviour) model was developed. Sessions and supporting resources were developed and refined via two iterative cycles of session and resource piloting, feedback, reflection and refinement. Decision on delivery and content were made by stakeholders (young people, teachers, parents, paediatricians) and all sites. Materials were translated to local languages. Site-specific adaptations to the language, content and supporting resources were made. Results: The "PRE-STARt" programme is eight 90-min interactive sessions with supporting curriculum and resources. Iterative development work provided valuable feedback on programme content and delivery. Conclusion: Reporting on the intervention development process, which includes stakeholder input, could yield a flexible approach for use in this emerging 'at risk' groups and their families