EMPRESAS ESTATAIS E FUNDOS GARANTIDORES DE CONTRATOS DE PARCERIAS PÚBLICO-PRIVADAS: impactos na organização administrativa brasileira

O presente artigo analisa as hipóteses de provisão de garantias ao parceiro-privado, contratos de parcerias público-privadas, por meio de empresas estatais e de fundos garantidores. O trabalho avalia a natureza jurídica e o regime jurídico dos fundos garantidores e das empresas estatais garantidoras de parcerias público-privadas, bem como analisa as características e o grau de segurança das garantidas prestadas por tais figuras

Association between prolonged corticosteroids use in COVID-19 and increased mortality in hospitalized patients : a retrospective study with inverse probability of treatment weighting analysis

Background: Previous studies have demonstrated a beneficial effect of early use of corticosteroids in patients with COVID-19. This study aimed to compare hospitalized patients with COVID-19 who received short-course corticosteroid treatment with those who received prolonged-course corticosteroid treatment to determine whether prolonged use of corticosteroids improves clinical outcomes, including mortality. Methods: This is a retrospective cohort study including adult patients with positive testing for Sars-CoV-2 hospitalized for more than 10 days. Data were obtained from electronic medical records. Patients were divided into two groups, according to the duration of treatment with corticosteroids: a short-course (10 days) and a prolonged-course (longer than 10 days) group. Inverse probability treatment weighting (IPTW) analysis was used to evaluate whether prolonged use of corticosteroids improved outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were hospital infection and the association of different doses of corticosteroids with hospital mortality. Restricted cubic splines were used to assess the nonlinear association between mortality and dose and duration of corticosteroids use. Results: We enrolled 1,539 patients with COVID-19. Among them, 1127 received corticosteroids for more than 10 days (prolonged-course group). The in-hospital mortality was higher in patients that received prolonged course corticosteroids (39.5% vs. 26%, p < 0.001). The IPTW revealed that prolonged use of corticosteroids significantly increased mortality [relative risk (RR) = 1.52, 95% confidence interval (95% CI): 1.24-1.89]. In comparison to short course treatment, the cubic spline analysis showed an inverted U-shaped curve for mortality, with the highest risk associated with the prolonged use at 30 days (RR = 1.50, 95% CI 1.21-1.78). Conclusions: Prolonged course of treatment with corticosteroids in hospitalized patients with COVID-19 was associated with higher mortality

Intervenção da terapia ocupacional em instituições de longa permanência para idosos a partir da percepção de terapeutas ocupacionais

: INTRODUCTION: The Long Stay Institution for the Elderly (LSIE) is a socio-sanitary service foreseen in the public policies of gerontology. The performance of Occupational Therapy (OT) in this field is still little explored in the literature. OBJECTIVE: To know and characterize the role of Occupational Therapist in LSIE. METHODS: Qualitative, exploratory and descriptive study. The snowball technique was used to locate and access the 10 Occupational Therapists with experience in an LSIE in the city of São Paulo. These were treated in August 2022. The results were treated in the light of thematic analysis by previous categories, corresponding to the questions contained in the semi-structured interview script, prepared by the researchers. RESULTS: The actions of the OT were characterized by: embracement of suffering in the institutionalization processes and experiences related to mourning; prescription of assistive technology equipment; environmental interventions and actions with formal and family caregivers. The actions aimed at: maintaining/rescuing autonomy, functionality and meaningful activities; improvement of physical-sensory-cognitive skills and favoring relational exchanges. Little understanding of the teams and managers about the performance of the OT was identified. CONCLUSION: The results obtained contribute to the visibility of the OT work in this service. &nbsp;INTRODUÇÃO: A Instituição de Longa Permanência para Idosos (ILPI) é um serviço sociossanitário previsto nas políticas públicas de gerontologia. A atuação da Terapia Ocupacional (TO) neste campo ainda é pouco explorada na literatura. OBJETIVO: Conhecer e caracterizar a atuação dos TOs em ILPI. MÉTODOS: Estudo qualitativo, exploratório e descritivo. Empregou-se a técnica bola-de-neve para localização e acesso aos 10 TOs com experiência em ILPI na cidade de São Paulo. Esses foram entrevistados no mês de agosto de 2022. Os resultados foram tratados à luz da análise temática por categorias prévias, correspondentes às questões contidas no roteiro semiestruturado de entrevistas, elaborado pelas pesquisadoras. RESULTADOS: As ações do TO caracterizavam-se pela/o(s): acolhimento do sofrimento nos processos de institucionalização e das vivências relacionadas ao luto; prescrição de equipamentos de tecnologia assistiva; intervenções ambientais e ações com cuidadores formais e familiares. As ações objetivavam: a manutenção/resgate da autonomia, funcionalidade e atividades significativas; melhora das habilidades físico-sensório-cognitivas e favorecer as trocas relacionais. Identificou-se pouca compreensão das equipes e chefias sobre a atuação do TO. CONCLUSÃO: Os resultados obtidos contribuem para a visibilidade do trabalho da TO neste serviço

Leishmania amazonensis promastigotes present two distinct modes of nucleus and kinetoplast segregation during cell cycle.

Abstract: Here, we show the morphological events associated with organelle segregation and their timing in the cell cycle of a reference strain of Leishmania (L.) amazonensis promastigotes, the main causative agent of Tegumentary leishmaniasis in the Americas. We show evidences that during the cell cycle, L. amazonensis promastigotes present two distinct modes of nucleus and kinetoplast segregation, which occur in different temporal order in different proportions of cells. We used DAPI-staining and EdU-labeling to monitor the segregation of DNA-containing organelles and DNA replication in wild-type parasites. The emergence of a new flagellum was observed using a specific monoclonal antibody. The results show that L. amazonensis cell cycle division is peculiar, with 65% of the dividing cells duplicating the kinetoplast before the nucleus, and the remaining 35% doing the opposite or duplicating both organelles concomitantly. In both cases, the new flagellum appeared during S to G2 phase in 1N1K cells and thus before the segregation of both DNA-containing organelles; however, we could not determine the exact timing of flagellar synthesis. Most of these results were confirmed by the synchronization of parasites using hydroxyurea. Altogether, our data show that during the cell cycle of L. amazonensis promastigotes, similarly to L. donovani, the segregation of nucleus and kinetoplast do not follow a specific order, especially when compared to other trypanosomatids, reinforcing the idea that this characteristic seems to be species-specific and may represent differences in cellular biology among members of the Leishmania genus

Aprendizaje basado en el proyecto de las especies nativas para la Fitorremediación de las aguas drenadas en la mina Tangana en el distrito de Huachocolpa, Huancavelica

The present research aims to evaluate the project-based learning of native species for the phytoremediation of drained waters in the Tangana mine and the bioaccumulation capacity of lead and cadmium through the species putacca (Family apiaceae) and cattail (Scirpus californicus), in the District of Huachocolpa of the Province and Department of Huancavelica (Peru). Applying the instrumental analytical methodology, satisfactory results were obtained for the environment, since both metals (cadmium and lead) were absorbed by these species. In this context, the following conclusions were obtained: a) The concentration of cadmium (Cd) and lead (Pb) in drained waters of the Tangana mine were 0.2661 mg Cd / l and 25.7220 mg Pb / l, the quantification of cadmium (Cd) and lead (Pb) concentration in the cattail species was 0.0007 mg Cd / Kg and 0.0037mg Pb / Kg, the quantification of the concentration of cadmium (Cd) and lead (Pb) in the putacca species was 0.0020 mg Cd / Kg and 0.0948 mg Pb / Kg). From the above it is inferred that putacca has a higher absorbance than cattail. b) Collaborative learning with the complement of ICTs allows students of different educational levels to reduce the gaps in access to information and interaction with experts in the field.La presente investigación tiene el objetivo de evaluar el aprendizaje basado en el proyecto de las especies nativas para la fitorremediación de las aguas drenadas en la mina Tangana y la capacidad de bioacumulacion de plomo y cadmio mediante las especies putacca (Familia apiaceae) y totora (Scirpus californicus), en el Distrito de Huachocolpa de la Provincia y Departamento de Huancavelica (Perú). Aplicando la metodología analítica instrumental, se obtuvieron resultados satisfactorios para el medio ambiente, pues ambos metales (cadmio y plomo) fueron absorbidos por estas especies. En este contexto, se obtuvieron las siguientes conclusiones: a) La concentración de cadmio (Cd) y plomo (Pb) en aguas drenadas de la mina Tangana fueron 0,2661 mg Cd/l y 25,7220 mg Pb/l, la cuantificación de concentración de cadmio (Cd) y plomo (Pb) en la especie totora fue 0,0007 mg Cd/Kg y de 0,0037mg Pb/Kg, la cuantificación de concentración de cadmio (Cd) y plomo (Pb) en la especie putacca fue 0,0020 mg Cd/Kg y 0,0948 mg Pb/Kg). De lo mencionado se infiere que la putacca posee mayor absorbancia que la totora. b) El aprendizaje colaborativo con el complemento de las TICs permite que los estudiantes de los diversos niveles educativos reduzcan las brechas de acceso a la información e interacción con los expertos en la materia

Risk of breast cancer and residential proximity to industrial installations: New findings from a multicase-control study (MCC-Spain)

Breast cancer is the most frequent tumor in women worldwide, although well-established risk factors account for 53%-55% of cases. Therefore, other risk factors, including environmental exposures, may explain the remaining variation. Our objective was to assess the relationship between risk of breast cancer and residential proximity to industries, according to categories of industrial groups and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain). Using the current residence of cases and controls, this study was restricted to small administrative divisions, including both breast cancer cases (452) and controls (1511) in the 10 geographical areas recruiting breast cancer cases. Distances were calculated from the respective woman's residences to the 116 industries located in the study area. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (between 1 km and 3 km) to industrial plants, adjusting for matching variables and other confounders. Excess risk (OR; 95%CI) of breast cancer was found near industries overall (1.30; 1.00-1.69 at 3 km), particularly organic chemical industry (2.12; 1.20-3.76 at 2.5 km), food/beverage sector (1.87; 1.26-2.78 at 3 km), ceramic (4.71; 1.62-13.66 at 1.5 km), surface treatment with organic solvents (2.00; 1.23-3.24 at 3 km), and surface treatment of plastic and metals (1.51; 1.06-2.14 at 3 km). By pollutants, the excess risk (OR; 95%CI) was detected near industries releasing pesticides (2.09; 1.14-3.82 at 2 km), and dichloromethane (2.09; 1.28-3.40 at 3 km). Our results suggest a possible increased risk of breast cancer in women living near specific industrial plants and support the need for more detailed exposure assessment of certain agents released by these plants.The authors thank all those who took part in this study providing questionnaire data. The study was partially funded by the “Acción Transversal del Cáncer", approved on the Spanish Ministry Council on the 11th October 2007, by the Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) – EVP-1178/14), by the Spain's Health Research Fund (Fondo de Investigación Sanitaria - FIS 12/01416), by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359 PS09/01286-León, PS09/00773-Cantabria, PS09/02078-Huelva, PS09/01903-Valencia, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/00613, PI15/00069, PI15/00914, PI15/01032), by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)), by the Fundación Marqués de Valdecilla (API 10/09), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), by the Junta de Castilla y León (LE22A10-2), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Regional Government of the Basque Country, by the Recercaixa (2010ACUP 00310), by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government DURSI grant 2017SGR723, by the University of Oviedo, and by the Fundación Caja de Ahorros de Asturias. ISGlobal is a member of the CERCA Program, Generalitat de Catalunya.S

Estudio de la respuesta inmune frente a la vacunación con virus respiratorio sincitial bovino (VRSB) inactivado en bovinos. Evaluación de la inmunidad pasiva

El objetivo de este trabajo fue evaluar el título y la duración de anticuerpos neutralizantes (AN) en vacas inmunizadas con una vacuna experimental inactivada para el virus respiratorio sincitial bovino (VRSB) y los niveles y la duración de los anticuerpos maternales anti-VRSB transferidos a través del calostrado en los terneros nacidos. Se inoculó un grupo de seis vacas preñadas con una vacuna inactivada de VRSB 90 y 60 días antes del parto. El grupo control estaba formado por seis vacas sin vacunar. Se obtuvieron muestras de suero de las vacas a los días 90, 60, 30 antes del parto y 0, 60 y 120 días posteriores al parto. Con respecto a los terneros, se recolectaron muestras de suero de ambos grupos a las 48 horas posparto y 30, 60, 90 y 120 días luego del nacimiento. La detección de anticuerpos específicos contra el VRSB se realizó mediante seroneutralización viral. En los terneros se determinaron proteínas totales e inmunoglobulina G total a las 48 horas posparto. Solo las vacas vacunadas seroconvirtieron a los 60 días después del refuerzo y los títulos de anticuerpos permanecieron elevados 180 días después de este. Los terneros recién nacidos mostraron una transferencia pasiva efectiva de anticuerpos maternos específicos para el VRSB. En este trabajo fue posible corroborar la inducción y duración de los anticuerpos específicos contra el VRSB en vacas vacunadas con una vacuna inactivada así como en sus respectivos terneros.The aim of this work was to evaluate the titer and duration of neutralizing antibodies in cows immunized with an inactivated experimental vaccine for BRSV and the levels and duration of anti-BRSV maternal antibodies in calves born. A group of six pregnant cows was inoculated with a inactivated BRSV vaccine, at 90 and 60 days before calving. As a control group, six animals were mock inoculated. Cows´ serum samples were obtained at days 90, 60, 30 before calving and at 0, 60 and 120 days postpartum. Sera from calves were obtained at 48-72 hours postpartum, 30, 60, 90 and 120 days after birth. The kinetic of serum specific antibodies from inoculated animals and newborn calves was analyzed by a serum neutralization assay. Only the vaccinated cows serocoverted 60 days post booster and antibody titers remained high 180 days post booster. Six newborn calves showed an effective passive transfer of specific BRSV maternal antibodies. In this work, it was possible to determine antibody levels against BRSV and their duration after vaccination of cows and calves born using an inactivated vaccine.EEA Marcos JuárezFil: Margineda, Carlos Augusto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Veterinarias; ArgentinaFil: Ferella, Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pérez Aguirreburualde, María Sol. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Sammarruco, Romina Ayelén. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Gonzalez, Diego. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Toledo, Gabriela Fernanda. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Dus Santos, Maria Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mozgovoj, Marina Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations

Intestinal barrier dysfunction; Intestinal glycocalyx; Mucosal nerve fibresDisfunción de la barrera intestinal; Glicocálix intestinal; Fibras nerviosas de la mucosaDisfunció de la barrera intestinal; Glicocàlix intestinal; Fibres nervioses de la mucosaIrritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.This study was funded in part by Fondo Europeo de Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Economía y Competitividad: CP18/00116 (C.M.), PI19/01643 (B.L.); PI17/01443 (D.G.); PI15/00301 (C.A.-C.), PI17/0190 (J.S.), PI19/01643 & CPII16/00031, (M.V.); CIBEREHD CB06/04/0021 (F.A., C.A.-C., J.S., M.V.); Ministerio de Educación, Dirección General de Investigación: SAF 2016-76648-R (F.A.); Agència de Gestió d’Ajuts Universitaris i de Recerca, de la Generalitat de Catalunya: 2014 SGR 1285 (F.A.); Vall d’Hebron Institut de Recerca, Programa de becas predoctorales Amics de Vall d’Hebron: PRED-VHIR-2016-34 (C.P.-C.), PRED-VHIR-2014-018 (M.F.), the Swedish Research Council dnr 2019-00653 (J.-P.G.M.), and the European Union’s Horizon research and innovation programme 2020, grant no. 848228 (E.E., A.R.-U., B.L., C.A.-C., J.S.)

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

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine : a pooled analysis of four randomised trials

Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5×10¹⁰ viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2×10¹⁰ viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAATpositive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24422 participants were recruited and vaccinated across the four studies, of whom 17178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4–74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3–85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59–0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3–91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0–69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18–55 years (GMR 2·32 [2·01–2·68]). Interpretation The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose