Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Phylogeny of Megasporoporia s.lat. and related genera of Poyporaceae: New genera, new species and new combinations

Several resupinate poroid Polyporaceae with dextrinoid skeletal hyphae and cylindrical, thin-walled basidiospores have been placed in Dichomitus and Megasporoporia. With the inclusion of DNA sequences, mostly from Chinese material, in the phylogeny of the genera, new genera were recognized, i.e., Megasporoporiella and Megasporia. In the current study, Jorgewrightia and Mariorajchenbergia are described as new genera in the Polyporaceae based on phylogenetic analyses of four gene regions: nuc rDNA ITS1-5.8S-ITS (ITS) and partial Large Subunit (28S), Translation Elongation Factor 1-alpha (TEF1), and RNA polymerase II second largest subunit (RPB2), mostly from Brazilian material. These new genera currently accommodate species formerly placed in Cerioporus, Dichomitus, Megasporia, Megasporoporiella and Pachykytospora. Dichomitus, Jorgewrightia, Mariorajchenbergia, Megasporia and Megasporoporia have mostly resupinate pale-colored basidiomata, poroid hymenophore, usually dextrinoid branched skeletal hyphae, and cylindrical basidiospores. These genera are difficult to differentiate on morphology alone and analyses based on sequences from at least two regions (ITS and 28S), as well as information about geographical distribution, are needed to separate them. Megasporia variabilicolor and Megasporoporia neosetulosa are described as new species, and one neotype and 20 new combinations are proposed. Synoptic tables including characteristics for 27 species from the five genera is presented

Enhanced remote areas communications: the missing scenario for 5G and beyond 5G networks

The next generation of mobile communication system will allow a plethora of new services and use cases. By offering support for high throughput connections, low latency response and massive number of connections, the fifth generation of the mobile network will trigger applications unseen in any other network. However, one important application scenario is not being properly addressed by the players responsible for the mobile networks' standardization, that is the remote and rural areas network. This scenario requires large cells with high throughput, flexibility to opportunistically exploit free bands below 1 GHz and spectrum agility to change the operational frequency when an incumbent is detected. Incipient actions are being considered for the Release 17 but based on the new radio specification as starting point. The limitations imposed by orthogonal waveforms in the physical layers hinder the exploitation of vacant TV channels in rural and remote areas. 5G-RANGE, a Brazil-Europe bilateral cooperation project, aims at conceiving, implementing and deploying an innovative mobile network, designed to provide reliable and cost-effective connection in these regions. This network can be seamlessly integrated with the other 5G scenarios, closing the connectivity gap between the urban, rural and remote areas. Hence, 5G-RANGE network is an interesting complementary solution for beyond 5G standards. This paper presents the major achievements of the 5G-RANGE project, from the design of the physical, medium access control and network layers, to the field demonstrations. The paper also covers the business models that can be used to make the deployment of this technology a reality.This work was supported in part by the European Union's Horizon 2020 Research and Innovation Programme under Grant 777137 (5G-RANGE Project), in part by the Centro de Pesquisa e Desenvolvimento em Tecnologias Digitais para Informação e Comunicação /Rede Nacional de Pesquisa (CTIC/RNP)/Ministério da Ciência, Tecnologia, Informação e Comunicação (MCTIC) through the 4a. Chamada Coordenada Brazil Europe (BR-EU) em Tecnologias da Informação e Comunicação (TICS), and in part by the Conselho Nacional de Desenvolvimento Cientí co e Tecnológico (CNPq)-Brazil under Grant 05085/2018-2. Computations were performed in part at the Center for Information Services and High Performance Computing at Technische Universität Dresden