Same-day SARS-CoV-2 antigen test screening in an indoor mass-gathering live music event: a randomised controlled trial

Background The banning of mass-gathering indoor events to prevent SARS-CoV-2 spread has had an important effect on local economies. Despite growing evidence on the suitability of antigen-detecting rapid diagnostic tests (Ag-RDT) for mass screening at the event entry, this strategy has not been assessed under controlled conditions. We aimed to assess the effectiveness of a prevention strategy during a live indoor concert. Methods We designed a randomised controlled open-label trial to assess the effectiveness of a comprehensive preventive intervention for a mass-gathering indoor event (a live concert) based on systematic same-day screening of attendees with Ag-RDTs, use of facial masks, and adequate air ventilation. The event took place in the Sala Apolo, Barcelona, Spain. Adults aged 18–59 years with a negative result in an Ag-RDT from a nasopharyngeal swab collected immediately before entering the event were randomised 1:1 (block randomisation stratified by age and gender) to either attend the indoor event for 5 hours or go home. Nasopharyngeal specimens used for Ag-RDT screening were analysed by real-time reverse-transcriptase PCR (RT-PCR) and cell culture (Vero E6 cells). 8 days after the event, a nasopharyngeal swab was collected and analysed by Ag-RDT, RT-PCR, and a transcription-mediated amplification test (TMA). The primary outcome was the difference in incidence of RT-PCR-confirmed SARS-CoV-2 infection at 8 days between the control and the intervention groups, assessed in all participants who were randomly assigned, attended the event, and had a valid result for the SARS-CoV-2 test done at follow-up. The trial is registered at ClinicalTrials.gov, NCT04668625. Findings Participant enrollment took place during the morning of the day of the concert, Dec 12, 2020. Of the 1140 people who responded to the call and were deemed eligible, 1047 were randomly assigned to either enter the music event (experimental group) or continue with normal life (control group). Of the 523 randomly assigned to the experimental group, 465 were included in the analysis of the primary outcome (51 did not enter the event and eight did not take part in the follow-up assessment), and of the 524 randomly assigned to the control group, 495 were included in the final analysis (29 did not take part in the follow-up). At baseline, 15 (3%) of 495 individuals in the control group and 13 (3%) of 465 in the experimental group tested positive on TMA despite a negative Ag-RDT result. The RT-PCR test was positive in one case in each group and cell viral culture was negative in all cases. 8 days after the event, two (<1%) individuals in the control arm had a positive Ag-RDT and PCR result, whereas no Ag-RDT nor RT-PCR positive results were found in the intervention arm. The Bayesian estimate for the incidence between the experimental and control groups was –0·15% (95% CI –0·72 to 0·44). Interpretation Our study provides preliminary evidence on the safety of indoor mass-gathering events during a COVID-19 outbreak under a comprehensive preventive intervention. The data could help restart cultural activities halted during COVID-19, which might have important sociocultural and economic implications.Primavera Sound Group and the #YoMeCorono InitiativePeer ReviewedPostprint (author's final draft

Monitoring SARS-CoV-2 variant transitions using differences in diagnostic cycle threshold values of target genes

Monitoring the emergence of new SARS-CoV-2 variants is important to detect potential risks of increased transmission or disease severity. We investigated the identification of SARS-CoV-2 variants from real-time reverse transcriptase polymerase chain reaction (RT-PCR) routine diagnostics data. Cycle threshold (Ct) values of positive samples were collected from April 2021 to January 2022 in the Northern Metropolitan Area of Barcelona (n = 15,254). Viral lineage identification from whole genome sequencing (WGS) was available for 4618 (30.3%) of these samples. Pairwise differences in the Ct values between gene targets (ΔCt) were analyzed for variants of concern or interest circulating in our area. A specific delay in the Ct of the N-gene compared to the RdRp-gene (ΔCt) was observed for Alpha, Delta, Eta and Omicron. Temporal differences in ΔCt correlated with the dynamics of viral replacement of Alpha by Delta and of Delta by Omicron according to WGS results. Using ΔCt, prediction of new variants of concern at early stages of circulation was achieved with high sensitivity and specificity (91.1% and 97.8% for Delta; 98.5% and 90.8% for Omicron). Thus, tracking population-wide trends in ΔCt values obtained from routine diagnostics testing in combination with WGS could be useful for real-time management and response to local epidemics

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

Caracterización y tipificación molecular de cepas de Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido (BLEE) aisladas en la Comunidad Valenciana

Introducción: Las betalactamasas de espectro extendido (BLEE) son enzimas producidas principalmente por la familia Enterobacteriaceae y se caracterizan porque inactivan a la práctica totalidad de los antibióticos betalactámicos. El aislamiento clínico de cepas productoras de BLEE es cada vez más frecuente en todo el mundo. Diferentes especies de Enterobacterales pueden ser productoras de BLEE, pero Klebsiella pneumoniae y Escherichia coli son las especies que las producen mayoritariamente. La realización de estudios de caracterización epidemiológica de las cepas productoras de BLEE es fundamental para detectar cualquier cambio en la resistencia y por tanto, para el control de su diseminación. En España, se han publicado trabajos donde se describe el tipo de enzimas BLEE que circulan pero estos no son recientes y los datos referidos a la Comunidad Valenciana son escasos y poco representativos. Objetivos: Estudio descriptivo y prospectivo de cepas de E. coli y K. pneumoniae BLEE+ remitidas por cuatro hospitales de la Comunidad Valenciana. Caracterización molecular de las enzimas BLEE y descripción y análisis de los clones circulantes. Material y métodos: La caracterización molecular de las enzimas BLEE se determinó mediante PCR y posterior secuenciación por el método Sanger. Para el estudio de clones y tipificación molecular se emplearon dos técnicas: Electroforesis en gel de campo pulsado (PFGE) y tipificación por secuenciación de múltiples loci (MLST). Resultados: Se estudiaron un total de 173 cepas de E. coli y K. pneumoniae BLEE+, incluyendo 133 (77%) E. coli y 40 (23%) K. pneumoniae. La familia BLEE más frecuente fue la CTX-M (89%) seguida de la SHV-12 (11%). Entre las cepas de K. pneumoniae BLEE+, las secuencias tipo predominantes fueron ST11, ST15, ST307. El clon E. coli ST131 fue muy prevalente. Se detectó en un 31,5% de las cepas, siendo el clon mayoritario entre las cepas productoras de CTX-M-15 (78%). Discusión: La aparición de Enterobacterales productores de BLEE se ha convertido en un problema de Salud Pública global debido a la dificultad de tratamiento antimicrobiano de las infecciones producidas por estas cepas. El resultado del PFGE reveló la existencia de brotes por K. pneumoniae BLEE+ en cada uno de los hospitales. Así como la existencia de diferentes pulsotipos entre las cepas de E. coli BLEE+. La tipificación molecular mediante MLST reveló la circulación del mismo clon en dos o más hospitales. Con respecto a E. coli, el clon ST131 está ampliamente distribuido en nuestro medio. Nuestros datos muestran, por tanto, la importancia de continuar con los estudios epidemiológicos de tipificación molecular de estas cepas y la caracterización de los enzimas que portan

Nanostructured Electroactive Materials with Large Charge Capacity: Direct Field Electrostimulation Through Connected and Non-connected Electrodes

Electric field stimulation protocols depend on the electrode material used, but the material characteristics are often not considered or sufficiently described for optimization. Furthermore, charge capacity is considered only in capacitor-like systems, without taking into account that intercalation materials offer an internal faradaic charge delivery advantage, with substantially less risk for biological systems. This chapter describes new materials with high charge capacities, appropriate electric field protocols for using them, and examples of neural cultures that can be used to elucidate the biological effects of fields. Mammalian neurons, neuron–astrocyte co-cultures, and amphibian spinal neurons are used in vitro, often as scratch wound models, to assess their potential for stimulating tissue repair. Importantly, remote control of dipoles induced in conducting implanted materials is shown to be a new promising approach and a breakthrough.The present work has been financed by the Ministry of Science of Spain (MAT2015-65192-R and RTI2018-097753-B-I00), Fundació Marató TV3 (110130/31), Severo Ochoa Program (SEV-2015-0496 and CEX2019-000917-S) and EU grant FP6-2004-NEST-C1 028473

Graphite, graphene oxide and graphene in hybrids with neural activity as electrodes

Trabajo presentado en el Latest Advances on Nanomaterials for Biomedical Applications (Nanobioapp), celebrado en Barcelona, España, del 21 al 23 de septiembre de 2015Peer Reviewe

Coatings of Nanostructured Pristine Graphene-IrOx Hybrids for Neural Electrodes: Layered Stacking and the role of non-oxygenated Graphene

The need to enhance charge capacity in neural stimulation-electrodes is promoting the formation of new materials and coatings. Among all the possible types of graphene, pristine graphene prepared by graphite electrochemical exfoliation, is used in this work to form a new nanostructured IrOx-graphene hybrid (IrOx-eG). Graphene is stabilized in suspension by IrOx nanoparticles without surfactants. Anodic electrodeposition results in coatings with much smaller roughness than IrOx-graphene oxide. Exfoliated pristine graphene (eG), does not electrodeposit in absence of iridium, but IrOx-nanoparticle adhesion on graphene flakes drives the process. IrOx-eG has a significantly different electronic state than graphene oxide, and different coordination for carbon. Electron diffraction shows the reflection features expected for graphene. IrOx 1-2 nm cluster/nanoparticles are oxohydroxo-species and adhere to 10 nm graphene platelets. eG induces charge storage capacity values five times larger than in pure IrOx, and if calculated per carbon atom, this enhancement is one order magnitude larger than the induced by graphene oxide. IrOx-eG coatings show optimal in vitro neural cell viability and function as cell culture substrates. The fully straightforward electrochemical exfoliation and electrodeposition constitutes a step towards the application of graphene in biomedical systems, expanding the knowledge of pristine graphene vs. graphene oxide, in bioelectrodes. © 2015 Elsevier B.V.This work was supported by grants from the Spanish MICINN (MAT2008-06643 and MAT2011-24363), Fundació Marató TV3 Grant (110130/31) and Instituto de Salud Carlos III (PI 13/1252)Peer Reviewe

Nanostructured materials for neural electrodes: hybrids of iridium oxide with graphene, nanotubes or conducting polymers

Trabajo presentado en la 5th Zing Conference in BioNanomaterials, celebrada en Carvoeiro, Portugal, del 25 al 28 de abril de 2015Intercalation materials that have been shown biocompatible in neural systems, are nanostructured for their use as electrodes. As the materials undergo faradaic reactions themselves, upon electric field application, they prevent radical formation and interfacial heating, while allowing cell growth and full functionality. Iridium oxide, IrOx, and conducting polymers are the basic materials that have been hybridized with carbon nanotubes, graphene, and graphite, graphene oxide and conducting PEDOT and polypyrrole polymers, in various forms1-5. Electrodeposition mechanisms are elucidated, while control of the multiple variables have allowed to reach optimal preprations on platinum. Charge storage capacities are increased in different magnitudes, while a clear difference is observed for some of the polymeric materials in terms of biocompatibility. Optimal behavior of cells is always observed on IrOx based materials, with respect to blank glass or platinum, while graphene and carbon nanotubes hybrids of IrOx are among the ones with best charge storage capacities an lower impedance up to middle frequencies.Peer Reviewe

Short-term electrostimulation enhancing neural repair in vitro using large charge capacity nanostructured electrodes

Electrostimulation of the neural system in functional or repair therapies requires new materials that protect the living system from electric field (EF) effects at the interface. Intercalation materials offer an alternative to radical formation during stimulation. Furthermore, nanostructuring of the electroactive material used as electrode offers an enlargement of the charge capacity which in turn involves changes in the EF effect. In this work, electric field stimulation of cortical neuron cultures has been applied in an in vitro model of lesion, namely, a physical scratch in the cell culture creates a cell-free area reminiscent of a lesion where new neurites grow. Regeneration of the “wound” zone upon EF stimulation is observed for various types of electrode materials, and compared to the spontaneous process and to platinum electrodes. Significantly, electric field effects are highly dependent on the electrode material used, even for the same charge delivered and similar impedance values. Electrode coatings with large charge storage capacity yield significantly better results than that of bare Pt electrodes. Neurite outgrowth at the scratched “wound” zone is lowest, below spontaneous regeneration, when using Pt electrodes. On the other hand, electroactive materials, such as bilayers of PEDOT and polypyrrole with lysine counterions or iridium oxide-pristine graphene hybrids, promote further regeneration. Beyond impedance considerations, the optimal material is the nanostructured one with the largest charge capacity, even at low charge deliveries. It is remarkable that IrOx-graphene hybrids reach regenerations above spontaneous case in very short stimulation times, for equal charge deliveries and potential protocols. The implications from the results suggest that EF application using these new coatings, may have an immediate use in safer electrostimulation procedures, and open routes for much needed neural repair.This work was supported by grants from the Spanish MEC (MAT2011-24363 and MAT2015-65192-R), Marató TV3 Grant (110130/31), CSIC Ref. 201560E053 and Instituto de Salud Carlos III (PI 10/453), and Cerca programme Generalitat de Catalunya (2014/SGR/625, 2014/SGR/1643), and Severo Ochoa Programme for Centres of Excellence in R&D (SEV-2015-0496). L. Ballesteros thanks financing from CONICYT Fondecyt Grant No. 3150143. The technical assistance of Elisenda Marti is acknowledged.Peer reviewe

Neural growth and functional development on new biocompatible hybrid materials

Póster presentado en el 15º Congreso Nacional de la Sociedad Española de NeuroCiencia, celebrado del 25 al 27 de septiembre de 2013 en Oviedo (España)Peer Reviewe