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

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Many-Antenna Full-Duplex with Fully Digital and Hybrid Beamforming Radios

Next generation wireless systems are expected to use a very large number of antennas at base stations (BSs). For example, the 3GPP has already included support for up to 128 antenna BSs for sub-6 GHz cellular systems in its standard specifications. The traditional approach to build many-antenna BSs is to connect each antenna element to a separate Tx-Rx RF chain (an architecture referred to as folly digital) . However, it is possible to reduce the cost and power consumption of the BS by connecting each RF chain to an array of antennas by using phased arrays or switched beam antennas (an architecture referred to as hybrid beamforming)

An Experiment-Based Comparison between Fully Digital and Hybrid Beamforming Radio Architectures for Many-Antenna Full-Duplex Wireless Communication

Full-duplex (FD) communication in many-antenna base stations (BSs) is hampered by self-interference (SI). This is because a FD node’s transmitting signal generates significant interference to its own receiver. Recent works have shown that it is possible to reduce/eliminate this SI in fully digital many-antenna systems, e.g., through transmit beamforming by using some spatial degrees of freedom to reduce SI instead of increasing the beamforming gain. On a parallel front, hybrid beamforming has recently emerged as a radio architecture that uses multiple antennas per FR chain. This can significantly reduce the cost of the end device (e.g., BS) but may also reduce the capacity or SI reduction gains of a fully digital radio system. This is because a fully digital radio architecture can change both the amplitude and phase of the wireless signal and send different data streams from each antenna element. Our goal in this paper is to quantify the performance gap between these two radio architectures in terms of SI cancellation and system capacity, particularly in multi-user MIMO setups. To do so, we experimentally compare the performance of a state-of-the-art fully digital many antenna FD solution to a hybrid beamforming architecture and compare the corresponding performance metrics leveraging a fully programmable many-antenna testbed and collecting over-the-air wireless channel data. We show that SI cancellation through beam design on a hybrid beamforming radio architecture can achieve capacity within 16% of that of a fully digital architecture. The performance gap further shrinks with a higher number of quantization bits in the hybrid beamforming system

An Experiment-Based Comparison between Fully Digital and Hybrid Beamforming Radio Architectures for Many-Antenna Full-Duplex Wireless Communication

Full-duplex (FD) communication in many-antenna base stations (BSs) is hampered by self-interference (SI). This is because a FD node’s transmitting signal generates significant interference to its own receiver. Recent works have shown that it is possible to reduce/eliminate this SI in fully digital many-antenna systems, e.g., through transmit beamforming by using some spatial degrees of freedom to reduce SI instead of increasing the beamforming gain. On a parallel front, hybrid beamforming has recently emerged as a radio architecture that uses multiple antennas per FR chain. This can significantly reduce the cost of the end device (e.g., BS) but may also reduce the capacity or SI reduction gains of a fully digital radio system. This is because a fully digital radio architecture can change both the amplitude and phase of the wireless signal and send different data streams from each antenna element. Our goal in this paper is to quantify the performance gap between these two radio architectures in terms of SI cancellation and system capacity, particularly in multi-user MIMO setups. To do so, we experimentally compare the performance of a state-of-the-art fully digital many antenna FD solution to a hybrid beamforming architecture and compare the corresponding performance metrics leveraging a fully programmable many-antenna testbed and collecting over-the-air wireless channel data. We show that SI cancellation through beam design on a hybrid beamforming radio architecture can achieve capacity within 16% of that of a fully digital architecture. The performance gap further shrinks with a higher number of quantization bits in the hybrid beamforming system

Rate Maximization in a UAV Based Full-Duplex Multi-User Communication Network Using Multi-Objective Optimization

In this paper, we study an unmanned-aerial-vehicle (UAV) based full-duplex (FD) multi-user communication network, where a UAV is deployed as a multiple-input–multiple-output (MIMO) FD base station (BS) to serve multiple FD users on the ground. We propose a multi-objective optimization framework which considers two desirable objective functions, namely sum uplink (UL) rate maximization and sum downlink (DL) rate maximization while providing quality-of-service to all the users in the communication network. A novel resource allocation multi-objective-optimization-problem (MOOP) is designed which optimizes the downlink beamformer, the beamwidth angle, and the 3D position of the UAV, and also the UL power of the FD users. The formulated MOOP is a non-convex problem which is generally intractable. To handle the MOOP, a weighted Tchebycheff method is proposed, which converts the problem to the single-objective-optimization-problem (SOOP). Further, an alternative optimization approach is used, where SOOP is converted in to multiple sub-problems and optimization variables are operated alternatively. The numerical results show a trade-off region between sum UL and sum DL rate, and also validate that the considered FD system provides substantial improvement over traditional HD systems

Rate Maximization in a UAV Based Full-Duplex Multi-User Communication Network Using Multi-Objective Optimization

In this paper, we study an unmanned-aerial-vehicle (UAV) based full-duplex (FD) multi-user communication network, where a UAV is deployed as a multiple-input–multiple-output (MIMO) FD base station (BS) to serve multiple FD users on the ground. We propose a multi-objective optimization framework which considers two desirable objective functions, namely sum uplink (UL) rate maximization and sum downlink (DL) rate maximization while providing quality-of-service to all the users in the communication network. A novel resource allocation multi-objective-optimization-problem (MOOP) is designed which optimizes the downlink beamformer, the beamwidth angle, and the 3D position of the UAV, and also the UL power of the FD users. The formulated MOOP is a non-convex problem which is generally intractable. To handle the MOOP, a weighted Tchebycheff method is proposed, which converts the problem to the single-objective-optimization-problem (SOOP). Further, an alternative optimization approach is used, where SOOP is converted in to multiple sub-problems and optimization variables are operated alternatively. The numerical results show a trade-off region between sum UL and sum DL rate, and also validate that the considered FD system provides substantial improvement over traditional HD systems