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

The beamed jet and quasar core of the distant blazar 4C 71.07

The object 4C 71.07 is a high-redshift blazar whose spectral energy distribution shows a prominent big blue bump and a strong Compton dominance. We present the results of a 2- yr multiwavelength campaign led by the Whole Earth Blazar Telescope (WEBT) to study both the quasar core and the beamed jet of this source. The WEBT data are complemented by ultraviolet and X-ray data from Swift, and by γ-ray data by Fermi. The big blue bump is modelled by using optical and near-infrared mean spectra obtained during the campaign, together with optical and ultraviolet quasar templates. We give prescriptions to correct the source photometry in the various bands for the thermal contribution, in order to derive the non-thermal jet flux. The role of the intergalactic medium absorption is analysed in both the ultraviolet and X-ray bands.We provide opacity values to deabsorb ultraviolet data, and derive a best-guess value for the hydrogen column density of Nbest H = 6.3 × 10 cmthrough the analysis of X-ray spectra.We estimate the disc and jet bolometric luminosities, accretion rate, and black hole mass. Light curves do not show persistent correlations among flux changes at different frequencies. We study the polarimetric behaviour and find no correlation between polarization degree and flux, even when correcting for the dilution effect of the big blue bump. Similarly, wide rotations of the electric vector polarization angle do not seem to be connected with the source activity.© 2019 The Author(s).We acknowledge financial contribution from the agreement ASI-INAF n.2017-14-H.0 and from the contract PRIN-SKA-CTA-INAF 2016. PR and SV acknowledge contract ASI-INAF I/004/11/0. We acknowledge support by Bulgarian National Science Programme 'Young Scientists and Postdoctoral Students 2019', Bulgarian National Science Fund under grant DN18-10/2017 and National RI Roadmap Projects DO1-157/28.08.2018 and DO1-153/28.08.2018 of the Ministry of Education and Science of the Republic of Bulgaria. GD and OV gratefully acknowledge the observing grant support from the Institute of Astronomy and Rozhen National Astronomical Observatory, Bulgarian Academy of Sciences via bilateral joint research project 'Study of ICRF radio-sources and fast variable astronomical objects' (head -G.Damljanovic). This work is a part of the Projects No. 176011 ('Dynamics and Kinematics of Celestial Bodies and Systems'), No. 176004 ('Stellar Physics'), and No. 176021 ('Visible and Invisible Matter in Nearby Galaxies: Theory and Observations') supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia. This research was partially supported by the Bulgarian National Science Fund of theMinistry of Education and Science under grants DN 08-1/2016, DN 18-13/2017, and KP-06-H28/3 (2018). The Skinakas Observatory is a collaborative project of the University of Crete, the Foundation for Research and Technology -Hellas, and the Max-Planck-Institut fur Extraterrestrische Physik. The St Petersburg University team acknowledges support from Russian Science Foundation grant no. 17-12-01029. The Abastumani team acknowledges financial support by the Shota Rustaveli National Science Foundation under contract FR/217950/16. This work was partly supported by the National Science Fund of the Ministry of Education and Science of Bulgaria under grant DN 08-20/2016, and by funds of the project RD-08-37/2019 of the University of Shumen. The Astronomical Observatory of the Autonomous Region of the Aosta Valley (OAVdA) is managed by the Fondazione Clement Fillietroz-ONLUS, which is supported by the Regional Government of the Aosta Valley, the Town Municipality of Nus and the Unite des Communes valdotaines Mont-Emilius'. The research at the OAVdA was partially funded by two 'Research and Education' grants from Fondazione CR