Parallel remote state preparation for fully device-independent verifiable blind quantum computation

We introduce a device-independent two-prover scheme in which a classical verifier is able to use a simple untrusted quantum measurement device (the client device) to securely delegate a quantum computation to an untrusted quantum server. To do this, we construct a parallel self-testing protocol to perform device-independent remote state preparation of $n$ qubits and compose this with the unconditionally secure universal verifiable blind quantum computation (VBQC) scheme of J. F. Fitzsimons and E. Kashefi [Phys. Rev. A 96, 012303 (2017)]. Our self-test achieves a multitude of desirable properties for the application we consider, giving rise to practical and fully device-independent VBQC. It certifies parallel measurements of all cardinal and intercardinal directions in the $XY$-plane as well as the computational basis, uses few input questions (of size logarithmic in $n$ for the client and a constant number communicated to the server), and requires only single-qubit measurements to be performed by the client device.Comment: 55 pages, 3 figure

Nonlocal games and their device-independent quantum applications

Device-independence is a property of certain protocols that allows one to ensure their proper execution given only classical interaction with devices and assuming the correctness of the laws of physics. This scenario describes the most general form of cryptographic security, in which no trust is placed in the hardware involved; indeed, one may even take it to have been prepared by an adversary. Many quantum tasks have been shown to admit device-independent protocols by augmentation with "nonlocal games". These are games in which noncommunicating parties jointly attempt to fulfil some conditions imposed by a referee. We introduce examples of such games and examine the optimal strategies of players who are allowed access to different possible shared resources, such as entangled quantum states. We then study their role in self-testing, private random number generation, and secure delegated quantum computation. Hardware imperfections are naturally incorporated in the device-independent scenario as adversarial, and we thus also perform noise robustness analysis where feasible. We first study a generalization of the Mermin–Peres magic square game to arbitrary rectangular dimensions. After exhibiting some general properties, these "magic rectangle" games are fully characterized in terms of their optimal win probabilities for quantum strategies. We find that for m×n magic rectangle games with dimensions m,n≥3, there are quantum strategies that win with certainty, while for dimensions 1×n quantum strategies do not outperform classical strategies. The final case of dimensions 2×n is richer, and we give upper and lower bounds that both outperform the classical strategies. As an initial usage scenario, we apply our findings to quantum certified randomness expansion to find noise tolerances and rates for all magic rectangle games. To do this, we use our previous results to obtain the winning probabilities of games with a distinguished input for which the devices give a deterministic outcome and follow the analysis of C. A. Miller and Y. Shi [SIAM J. Comput. 46, 1304 (2017)]. Self-testing is a method to verify that one has a particular quantum state from purely classical statistics. For practical applications, such as device-independent delegated verifiable quantum computation, it is crucial that one self-tests multiple Bell states in parallel while keeping the quantum capabilities required of one side to a minimum. We use our 3×n magic rectangle games to obtain a self-test for n Bell states where one side needs only to measure single-qubit Pauli observables. The protocol requires small input sizes [constant for Alice and O(log n) bits for Bob] and is robust with robustness O(n⁵/²√ε), where ε is the closeness of the ideal (perfect) correlations to those observed. To achieve the desired self-test, we introduce a one-side-local quantum strategy for the magic square game that wins with certainty, we generalize this strategy to the family of 3×n magic rectangle games, and we supplement these nonlocal games with extra check rounds (of single and pairs of observables). Finally, we introduce a device-independent two-prover scheme in which a classical verifier can use a simple untrusted quantum measurement device (the client device) to securely delegate a quantum computation to an untrusted quantum server. To do this, we construct a parallel self-testing protocol to perform device-independent remote state preparation of n qubits and compose this with the unconditionally secure universal verifiable blind quantum computation (VBQC) scheme of J. F. Fitzsimons and E. Kashefi [Phys. Rev. A 96, 012303 (2017)]. Our self-test achieves a multitude of desirable properties for the application we consider, giving rise to practical and fully device-independent VBQC. It certifies parallel measurements of all cardinal and intercardinal directions in the XY-plane as well as the computational basis, uses few input questions (of size logarithmic in n for the client and a constant number communicated to the server), and requires only single-qubit measurements to be performed by the client device

Neuropathology of wild-type and nef-attenuated T cell tropic simian immunodeficiency virus (SIVmac32H) and macrophage tropic neurovirulent SIVmac17E-Fr in cynomolgus macaques

The neuropathology of simian immunodeficiency (SIV) infection in cynomolgus macaques (Macaca fascicularis) was investigated following infection with either T cell tropic SIVmacJ5, SIVmacC8 or macrophage tropic SIVmac17E-Fr. Formalin fixed, paraffin embedded brain tissue sections were analysed using a combination of in situ techniques. Macaques infected with either wild-type SIVmacJ5 or neurovirulent SIVmac17E-Fr showed evidence of neuronal dephosphorylation, loss of oligodendrocyte and CCR5 staining, lack of microglial MHC II expression, infiltration by CD4+ and CD8+ T cells and mild astrocytosis. SIVmacJ5-infected animals exhibited activation of microglia whilst those infected with SIVmac17E-Fr demonstrated a loss of microglia staining. These results are suggestive of impaired central nervous system (CNS) physiology. Furthermore, infiltration by T cells into the brain parenchyma indicated disruption of the blood brain barrier (BBB). Animals infected with the Δnef-attenuated SIVmacC8 showed microglial activation and astrogliosis indicative of an inflammatory response, lack of MHC II and CCR5 staining and infiltration by CD8+ T cells. These results demonstrate that the SIV infection of cynomolgus macaque can be used as a model to replicate the range of CNS pathologies observed following HIV infection of humans and to investigate the pathogenesis of HIV associated neuropathology

The Preterm Clinical Network (PCN) Database: a web-based systematic method of collecting data on the care of women at risk of preterm birth

Background: Despite much research effort, there is a paucity of conclusive evidence in the field of preterm birth prediction and prevention. The methods of monitoring and prevention strategies offered to women at risk vary considerably around the UK and depend on local maternity care provision. It is becoming increasingly recognised that this experience and knowledge, if captured on a larger scale, could be a utilized as a valuable source of evidence for others. The UK Preterm Clinical Network (UKPCN) was established with the aim of improving care and outcomes for women at risk of preterm birth through the sharing of a wealth of experience and knowledge, as well as the building of clinical and research collaboration. The design and development of a bespoke internet-based database was fundamental to achieving this aim. Method: Following consultation with UKPCN members and agreement on a minimal dataset, the Preterm Clinical Network (PCN) Database was constructed to collect data from women at risk of preterm birth and their children. Information Governance and research ethics committee approval was given for the storage of historical as well as prospectively collected data. Collaborating centres have instant access to their own records, while use of pooled data is governed by the PCN Database Access Committee. Applications are welcomed from UKPCN members and other established research groups. The results of investigations using the data are expected to provide insights into the effectiveness of current surveillance practices and preterm birth interventions on a national and international scale, as well as the generation of ideas for innovation and research. To date, 31 sites are registered as Data Collection Centres, four of which are outside the UK. Conclusion: This paper outlines the aims of the PCN Database along with the development process undertaken from the initial idea to live launch

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

TRY plant trait database – enhanced coverage and open access

Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.Rest of authors: Decky Junaedi, Robert R. Junker, Eric Justes, Richard Kabzems, Jeffrey Kane, Zdenek Kaplan, Teja Kattenborn, Lyudmila Kavelenova, Elizabeth Kearsley, Anne Kempel, Tanaka Kenzo, Andrew Kerkhoff, Mohammed I. Khalil, Nicole L. Kinlock, Wilm Daniel Kissling, Kaoru Kitajima, Thomas Kitzberger, Rasmus Kjøller, Tamir Klein, Michael Kleyer, Jitka Klimešová, Joice Klipel, Brian Kloeppel, Stefan Klotz, Johannes M. H. Knops, Takashi Kohyama, Fumito Koike, Johannes Kollmann, Benjamin Komac, Kimberly Komatsu, Christian König, Nathan J. B. Kraft, Koen Kramer, Holger Kreft, Ingolf Kühn, Dushan Kumarathunge, Jonas Kuppler, Hiroko Kurokawa, Yoko Kurosawa, Shem Kuyah, Jean-Paul Laclau, Benoit Lafleur, Erik Lallai, Eric Lamb, Andrea Lamprecht, Daniel J. Larkin, Daniel Laughlin, Yoann Le Bagousse-Pinguet, Guerric le Maire, Peter C. le Roux, Elizabeth le Roux, Tali Lee, Frederic Lens, Simon L. Lewis, Barbara Lhotsky, Yuanzhi Li, Xine Li, Jeremy W. Lichstein, Mario Liebergesell, Jun Ying Lim, Yan-Shih Lin, Juan Carlos Linares, Chunjiang Liu, Daijun Liu, Udayangani Liu, Stuart Livingstone, Joan Llusià, Madelon Lohbeck, Álvaro López-García, Gabriela Lopez-Gonzalez, Zdeňka Lososová, Frédérique Louault, Balázs A. Lukács, Petr Lukeš, Yunjian Luo, Michele Lussu, Siyan Ma, Camilla Maciel Rabelo Pereira, Michelle Mack, Vincent Maire, Annikki Mäkelä, Harri Mäkinen, Ana Claudia Mendes Malhado, Azim Mallik, Peter Manning, Stefano Manzoni, Zuleica Marchetti, Luca Marchino, Vinicius Marcilio-Silva, Eric Marcon, Michela Marignani, Lars Markesteijn, Adam Martin, Cristina Martínez-Garza, Jordi Martínez-Vilalta, Tereza Mašková, Kelly Mason, Norman Mason, Tara Joy Massad, Jacynthe Masse, Itay Mayrose, James McCarthy, M. Luke McCormack, Katherine McCulloh, Ian R. McFadden, Brian J. McGill, Mara Y. McPartland, Juliana S. Medeiros, Belinda Medlyn, Pierre Meerts, Zia Mehrabi, Patrick Meir, Felipe P. L. Melo, Maurizio Mencuccini, Céline Meredieu, Julie Messier, Ilona Mészáros, Juha Metsaranta, Sean T. Michaletz, Chrysanthi Michelaki, Svetlana Migalina, Ruben Milla, Jesse E. D. Miller, Vanessa Minden, Ray Ming, Karel Mokany, Angela T. Moles, Attila Molnár V, Jane Molofsky, Martin Molz, Rebecca A. Montgomery, Arnaud Monty, Lenka Moravcová, Alvaro Moreno-Martínez, Marco Moretti, Akira S. Mori, Shigeta Mori, Dave Morris, Jane Morrison, Ladislav Mucina, Sandra Mueller, Christopher D. Muir, Sandra Cristina Müller, François Munoz, Isla H. Myers-Smith, Randall W. Myster, Masahiro Nagano, Shawna Naidu, Ayyappan Narayanan, Balachandran Natesan, Luka Negoita, Andrew S. Nelson, Eike Lena Neuschulz, Jian Ni, Georg Niedrist, Jhon Nieto, Ülo Niinemets, Rachael Nolan, Henning Nottebrock, Yann Nouvellon, Alexander Novakovskiy, The Nutrient Network, Kristin Odden Nystuen, Anthony O'Grady, Kevin O'Hara, Andrew O'Reilly-Nugent, Simon Oakley, Walter Oberhuber, Toshiyuki Ohtsuka, Ricardo Oliveira, Kinga Öllerer, Mark E. Olson, Vladimir Onipchenko, Yusuke Onoda, Renske E. Onstein, Jenny C. Ordonez, Noriyuki Osada, Ivika Ostonen, Gianluigi Ottaviani, Sarah Otto, Gerhard E. Overbeck, Wim A. Ozinga, Anna T. Pahl, C. E. Timothy Paine, Robin J. Pakeman, Aristotelis C. Papageorgiou, Evgeniya Parfionova, Meelis Pärtel, Marco Patacca, Susana Paula, Juraj Paule, Harald Pauli, Juli G. Pausas, Begoña Peco, Josep Penuelas, Antonio Perea, Pablo Luis Peri, Ana Carolina Petisco-Souza, Alessandro Petraglia, Any Mary Petritan, Oliver L. Phillips, Simon Pierce, Valério D. Pillar, Jan Pisek, Alexandr Pomogaybin, Hendrik Poorter, Angelika Portsmuth, Peter Poschlod, Catherine Potvin, Devon Pounds, A. Shafer Powell, Sally A. Power, Andreas Prinzing, Giacomo Puglielli, Petr Pyšek, Valerie Raevel, Anja Rammig, Johannes Ransijn, Courtenay A. Ray, Peter B. Reich, Markus Reichstein, Douglas E. B. Reid, Maxime Réjou-Méchain, Victor Resco de Dios, Sabina Ribeiro, Sarah Richardson, Kersti Riibak, Matthias C. Rillig, Fiamma Riviera, Elisabeth M. R. Robert, Scott Roberts, Bjorn Robroek, Adam Roddy, Arthur Vinicius Rodrigues, Alistair Rogers, Emily Rollinson, Victor Rolo, Christine Römermann, Dina Ronzhina, Christiane Roscher, Julieta A. Rosell, Milena Fermina Rosenfield, Christian Rossi, David B. Roy, Samuel Royer-Tardif, Nadja Rüger, Ricardo Ruiz-Peinado, Sabine B. Rumpf, Graciela M. Rusch, Masahiro Ryo, Lawren Sack, Angela Saldaña, Beatriz Salgado-Negret, Roberto Salguero-Gomez, Ignacio Santa-Regina, Ana Carolina Santacruz-García, Joaquim Santos, Jordi Sardans, Brandon Schamp, Michael Scherer-Lorenzen, Matthias Schleuning, Bernhard Schmid, Marco Schmidt, Sylvain Schmitt, Julio V. Schneider, Simon D. Schowanek, Julian Schrader, Franziska Schrodt, Bernhard Schuldt, Frank Schurr, Galia Selaya Garvizu, Marina Semchenko, Colleen Seymour, Julia C. Sfair, Joanne M. Sharpe, Christine S. Sheppard, Serge Sheremetiev, Satomi Shiodera, Bill Shipley, Tanvir Ahmed Shovon, Alrun Siebenkäs, Carlos Sierra, Vasco Silva, Mateus Silva, Tommaso Sitzia, Henrik Sjöman, Martijn Slot, Nicholas G. Smith, Darwin Sodhi, Pamela Soltis, Douglas Soltis, Ben Somers, Grégory Sonnier, Mia Vedel Sørensen, Enio Egon Sosinski Jr, Nadejda A. Soudzilovskaia, Alexandre F. Souza, Marko Spasojevic, Marta Gaia Sperandii, Amanda B. Stan, James Stegen, Klaus Steinbauer, Jörg G. Stephan, Frank Sterck, Dejan B. Stojanovic, Tanya Strydom, Maria Laura Suarez, Jens-Christian Svenning, Ivana Svitková, Marek Svitok, Miroslav Svoboda, Emily Swaine, Nathan Swenson, Marcelo Tabarelli, Kentaro Takagi, Ulrike Tappeiner, Rubén Tarifa, Simon Tauugourdeau, Cagatay Tavsanoglu, Mariska te Beest, Leho Tedersoo, Nelson Thiffault, Dominik Thom, Evert Thomas, Ken Thompson, Peter E. Thornton, Wilfried Thuiller, Lubomír Tichý, David Tissue, Mark G. Tjoelker, David Yue Phin Tng, Joseph Tobias, Péter Török, Tonantzin Tarin, José M. Torres-Ruiz, Béla Tóthmérész, Martina Treurnicht, Valeria Trivellone, Franck Trolliet, Volodymyr Trotsiuk, James L. Tsakalos, Ioannis Tsiripidis, Niklas Tysklind, Toru Umehara, Vladimir Usoltsev, Matthew Vadeboncoeur, Jamil Vaezi, Fernando Valladares, Jana Vamosi, Peter M. van Bodegom, Michiel van Breugel, Elisa Van Cleemput, Martine van de Weg, Stephni van der Merwe, Fons van der Plas, Masha T. van der Sande, Mark van Kleunen, Koenraad Van Meerbeek, Mark Vanderwel, Kim André Vanselow, Angelica Vårhammar, Laura Varone, Maribel Yesenia Vasquez Valderrama, Kiril Vassilev, Mark Vellend, Erik J. Veneklaas, Hans Verbeeck, Kris Verheyen, Alexander Vibrans, Ima Vieira, Jaime Villacís, Cyrille Violle, Pandi Vivek, Katrin Wagner, Matthew Waldram, Anthony Waldron, Anthony P. Walker, Martyn Waller, Gabriel Walther, Han Wang, Feng Wang, Weiqi Wang, Harry Watkins, James Watkins, Ulrich Weber, James T. Weedon, Liping Wei, Patrick Weigelt, Evan Weiher, Aidan W. Wells, Camilla Wellstein, Elizabeth Wenk, Mark Westoby, Alana Westwood, Philip John White, Mark Whitten, Mathew Williams, Daniel E. Winkler, Klaus Winter, Chevonne Womack, Ian J. Wright, S. Joseph Wright, Justin Wright, Bruno X. Pinho, Fabiano Ximenes, Toshihiro Yamada, Keiko Yamaji, Ruth Yanai, Nikolay Yankov, Benjamin Yguel, Kátia Janaina Zanini, Amy E. Zanne, David Zelený, Yun-Peng Zhao, Jingming Zheng, Ji Zheng, Kasia Ziemińska, Chad R. Zirbel, Georg Zizka, Irié Casimir Zo-Bi, Gerhard Zotz, Christian Wirth.Max Planck Institute for Biogeochemistry; Max Planck Society; German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig; International Programme of Biodiversity Science (DIVERSITAS); International Geosphere-Biosphere Programme (IGBP); Future Earth; French Foundation for Biodiversity Research (FRB); GIS ‘Climat, Environnement et Société'.http://wileyonlinelibrary.com/journal/gcbhj2021Plant Production and Soil Scienc

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