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

Phylogenomics, Biogeography, and Morphometrics Reveal Rapid Phenotypic Evolution in Pythons After Crossing Wallace's Line

Ecological opportunities can be provided to organisms that cross stringent biogeographic barriers towards environments with new ecological niches. Wallace’s and Lyddeker’s lines are arguably the most famous biogeographic barriers, separating the Asian and Australo-Papuan biotas. One of the most ecomorphologically diverse groups of reptiles, the pythons, is distributed across these lines, and are remarkably more diverse in phenotype and ecology east of Lydekker’s line in Australo-Papua. We used an anchored hybrid enrichment approach, with near complete taxon sampling, to extract mitochondrial genomes and 376 nuclear loci to resolve and date their phylogenetic history. Biogeographic reconstruction demonstrates that they originated in Asia around 38-45 Ma and then invaded Australo-Papua around 23 Ma. Australo-Papuan pythons display a sizeable expansion in morphological space, with shifts towards numerous new adaptive optima in head and body shape, coupled with the evolution of new micro-habitat preferences. We provide an updated taxonomy of pythons and our study also demonstrates how ecological opportunity following colonization of novel environments can promote morphological diversification in a formerly ecomorphologically conservative group. [Adaptive radiation; anchored hybrid enrichment; biogeography; morphometrics; snakes.]the Fundação de Amparo à Pesquisa do Estado de São Paulo Grant BIOTA-FAPESP 2011/50206-9 to HZ. DE was supported by a BECAS CHILE-CONICYT scholarshi

Data from: The impact of anchored phylogenomics and taxon sampling on phylogenetic inference in narrow-mouthed frogs (Anura, Microhylidae)

Despite considerable progress in unravelling the phylogenetic relationships of microhylid frogs, relationships among subfamilies remain largely unstable and many genera are not demonstrably monophyletic. Here, we used five alternative combinations of DNA sequence data (ranging from seven loci for 48 taxa to up to 73 loci for as many as 142 taxa) generated using the anchored phylogenomics sequencing method (66 loci, derived from conserved genome regions, for 48 taxa) and Sanger sequencing (seven loci for up to 142 taxa) to tackle this problem. We assess the effects of character sampling, taxon sampling, analytical methods and assumptions in phylogenetic inference of microhylid frogs. The phylogeny of microhylids shows high susceptibility to different analytical methods and datasets used for the analyses. Clades inferred from maximum-likelihood are generally more stable across datasets than those inferred from parsimony. Parsimony trees inferred within a tree-alignment framework are generally better resolved and better supported than those inferred within a similarity-alignment framework, even under the same cost matrix (equally weighted) and same treatment of gaps (as a fifth nucleotide state). We discuss potential causes for these differences in resolution and clade stability among discovery operations. We also highlight the problem that commonly used algorithms for model-based analyses do not explicitly model insertion and deletion events (i.e. gaps are treated as missing data). Our results corroborate the monophyly of Microhylidae and most currently recognized subfamilies but fail to provide support for relationships among subfamilies. Several taxonomic updates are provided, including naming of two new subfamilies, both monotypic

Supporting Information - Text S2

Trimming patterns for Anchored Phylogenomic loci. This file is the same as the one available at Wiley Online Library and published together with the manuscript (supporting Information Text S2). It is reproduced here as a backup for the original

Datasets

Contain all five alternative datasets used for the analyses. Description of the datasets are given in the text (see Figure 2)

Trees

Tree files (.tre) of alternative analyses for all five distinct datasets. Files contain only a single tree (consensus tree if more than one equally parsimonious tree was recovered) and include support values. Jackknife for parsimony analyses, Bootstrap for maximum likelihood analyses

Supporting Informatoion - Text S1

Material and methods -- additional details on sequencing methods; primer sequences and references. This file is the same as the one available at Wiley Online Library and published together with the manuscript (supporting Information Text S1). It is reproduced here as a backup for the original

Supporting Information - Table S1

Metadata for samples included in phylogenetic analyses -- Voucher Specimen, Locality, GenBank Accession Number. This file is the same as the one available at Wiley Online Library and published together with the manuscript (supporting Information Table S1). It is reproduced here as a backup for the original