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

Nanomaterials in the Environment: Perspectives on in Vivo Terrestrial Toxicity Testing

Over the last decade, engineered nanomaterials (NMs) brought a revolutionary development in many sectors of human life including electronics, paints, textiles, food, agriculture, and health care. However, the exponential growth in the number of NMs applications resulted in uncertainties regarding their environmental impacts. Currently, the common approach for assessing the toxicity of NMs such as, carbon—(fullerenes, single- and multi-walled carbon nanotubes), mineral—(gold and silver nanoparticles, cerium and zinc oxide, silicon and titanium dioxide), and organic-based NMs (dendrimers) includes standard guidelines applied to all chemical compounds. Nevertheless, NMs differ from traditional materials as their physicochemical and surface properties influence the toxic rather than their composition alone. Considering such NMs specificities, adaptations in some methods are necessary to ensure that environmental and human health risks are accurately investigated. In this context, the focus of this mini-review is to summarize the current knowledge in nanotoxicology regarding relevant organisms and experimental assays for assessing the terrestrial toxicity of NMs

Effect of maternal heat-stress on follicular growth and oocyte competence in Bos indicus cattle

The objective was to determine whether exposure of Gir (Bos indicus) cows to heat-stress (HS) causes immediate and delayed deleterious effect on follicular dynamics, hormonal profile and oocyte competence. The cows were kept in tie-stalls for an adaptive thermoneutral period of 28 days (Phase I, Days -28 to -1). In Phase II (Days 0-28) cows were randomly allocated into control (CG, n = 5) and HS (HS, n = 5) treatments. The HS cows were placed in an environmental chamber at '38 GRAUS'C and 80% relative humidity (RH) during the day and '30 GRAUS'C, 80% RH during the night for 28 days. The CG group was maintained in shaded tie-stalls (ambient temperature) for 28 days. During Phase III (Days 28-147) animals were placed in tie-stalls (Days 28-42) followed by pasture (Days 42-147) under thermoneutrality. In each phase, weekly ovum pick up (OPU) sessions were to evaluate follicular development, morphology of cumulus-oocyte complexes (COCs), and developmental competence after in vitro maturation, fertilization, and culture. Serum concentrations of progesterone ('P IND. 4') and cortisol were evaluated by radioimmunoassay. Exposure of Gir cows to HS had no immediate effect on reproductive function, but exerted a delayed deleterious effect on ovarian follicular growth, hormone concentrations, and oocyte competence. Heat-stress increased the diameter of the first and second largest follicles from Days 28 to 49. Indeed, HS increased the number of >9 mm follicles (characterized as follicular codominance) during this phase. Cows exposed to HS had longer periods of non-cyclic activity ('P IND. 4' < 1 ng/mL), as well as shorter estrous cycles. However, HS did not affect cortisol concentration as compared to CG. Although HS had no significant effect on cleavage rate, it reduced blastocyst development during Phase III. In conclusion, long-term exposure of B. indicus cattle to HS had a delayed deleterious effect on ovarian follicular dynamics and oocyte competenc