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

Qualidade da atenção básica mediante internações evitáveis no Sul do Brasil

Realizou-se estudo para avaliar mediante taxa de internações hospitalares evitáveis a qualidade dos cuidados oferecidos pela rede básica de saúde em Pelotas, Rio Grande do Sul, Brasil, no período entre 1995 a 2004. Foram consideradas como internações evitáveis: diabetes mellitus, insuficiência cardíaca, hipertensão arterial sistêmica, doença pulmonar obstrutiva crônica e doenças imunopreveníveis (poliomielite, difteria, tétano, coqueluche, sarampo). Foram incluídos homens e mulheres de 20 a 59 anos. Os percentuais entre as mulheres foram superiores aos encontrados nos homens. Foi observada uma diminuição dos percentuais de internações tanto nos homens como nas mulheres no decorrer do período. Mesmo após a padronização direta revelou-se que as taxas de internação de Pelotas foram inferiores às do Rio Grande do Sul. Os custos das hospitalizações evitáveis acompanharam a queda observada nas taxas de internações. Aparentemente, a diminuição verificada nas taxas de internações evitáveis pode estar relacionada à qualificação dos serviços de atenção básica. Contudo, os resultados podem ser conseqüências do financiamento do sistema de saúde. Os valores de pagamento desses procedimentos são baixos e podem estar direcionando os hospitais a uma diminuição da oferta de leitos

High Prevalence of Hepatitis B Subgenotype D4 in Northeast Brazil: an Ancient Relic from African Continent?

Introduction. Hepatitis B virus (HBV) infection leads to a chronic liver disease that is distributed worldwide. The characterization of HBV into genotypes/subgenotypes is not only a mere procedure for distinguishing different HBV strains around the world because determining their geographic distribution is crucial to understanding their spread across the world.Material and methods. We characterized different HBV genotypes and subgenotypes in five municipalities located in northeastern Maranhão, in the Brazilian north Atlantic coast. 92 HBsAg-positive individuals were submitted to PCR (polymerase chain reaction). Fifty samples were sequenced using automated Sanger sequencing and classified by phylogenetic methods.Results. Subgenotypes D4 and A1 were found in 42 (84%) and eight (16%) samples, respectively. To our knowledge, this is the first study to describe a high frequency of subgenotype D4 in any population. Subgenotype A1 is frequently found across Brazil, but D4 has been rarely detected and only in a few Brazilian states. This study shows the characterization of HBV subgenotypes from a population based study in the state of Maranhão, particularly in populations that do not have frequent contact with populations from other regions of the world.Conclusion. Our findings showed a HBV subgenotype profile that probably reflect the viruses that were brought with the slave trade from Africa to Maranhão. This study also reinforces the need to evaluate the status of HBV dispersion not only in large urban centers, but also in the hinterland, to enable the implementation of effective control and treatment measures

Hepatitis D and B virus genotypes in chronically infected patients from the Eastern Amazon Basin

Hepatitis D virus (HDV) is a defective hepatotropic virus whose infectivity is dependent on hepatitis B virus (HBV). HDV super- or co-infiection leads to an increased risk of fulminant hepatitis or progression to severe chronic liver disease in HBV infected patients. The Brazilian Amazon Basin has been reported to be endemic for HBV and HDV, especially in the Western Amazon Basin. In this region, HDV infection is frequently associated with acute fulminant hepatitis with characteristic histologic features. HDV is classified into seven major clades (HDV-1 to HDV-7) and HBV is subdivided into eight genotypes (A-H). HDV and HBV genotypes have been shown to have a distinct geographic distribution. The aim of this study was to determine the HBV and HDV genotypes harbored by chronically infected patients from the Eastern Amazon Basin, Brazil. We studied 17 serum samples from HBV and HDV chronically infected patients admitted to a large public hospital (Santa Casa de Misericordia) at Belem, state of Para, Brazil, between 1994 and 2002. HDV-3 and HBV genotype A (subtype adw2) have been identified in all cases, in contrast to previous studies from other regions of the Amazon, where HBV genotype F has been found co-infecting patients that harbored HDV-3. The HDV-3/HBV-A co-infection suggests that there is not a specific interaction between HBV and HDV genotypes, and co-infection might merely reflect the most frequent genotypes found in a particular geographic area. The analysis of the carboxy-terminal region of the large hepatitis D antigen (L-HDAg), which interacts with the hepatitis B surface antigen (HBsAg) and is essential for HDV assembly, showed some diversity between the different isolates from the Eastern Amazon. This diversity is not observed among HDV-3 sequences from other South American regions. (C) 2008 Elsevier B.V. All rights reserved

Aerobic training reduces immune cell recruitment and cytokine levels in adipose tissue in obese mice

Obesity is associated with an energy imbalance that results from excessive energy intake, low diet quality and a sedentary lifestyle. In this regard, the increased consumption of a high-refined carbohydrate diet (HC) is strongly related to higher adiposity and low-grade inflammation. Aerobic training is a well-known non-pharmacological intervention to treat obesity and metabolic disturbances. However, the mechanisms through which aerobic training ameliorates the low-grade inflammation induced by the HC diet need to be further investigated. Herein, our hypothesis was that aerobic training would decrease the recruitment of leukocytes in the adipose tissue thereby reducing the levels of cytokines and improving metabolism in mice fed the HC diet. Male Balb/c were assigned to the following groups: control non-trained (C-NT), control trained (C-T), HC-NT and HC-T. Mice were submitted to moderate-intensity training sessions that consisted of running 60 min/day for 8 weeks. The intravital microscopy technique was performed in vivo in anesthetized mice to visualize the microvasculature of the adipose tissue. The HC diet induced obesity and increased the influx of immune cells into the adipose tissue. In contrast, HC-T mice presented a lower adiposity and adipocyte area. Furthermore, HC-T mice showed an increased resting energy expenditure, a decreased recruitment of immune cells in the adipose tissue, reduced cytokine levels, and ameliorated hyperglycemia and fatty liver deposition relative to HC-NT mice. Collectively, our data enhance the understanding about the anti-inflammatory effect of aerobic training and shed light on the adipose tissue-mediated mechanisms by which training promotes a healthier metabolic profile.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Predictors of clinical evolution of SARS-CoV-2 infection in hematological patients: A SYSTEMATIC REVIEW AND META-ANALYSIS

Main aim of this systematic review is to quantify the risk and identify predictors of clinical evolution of SARS-CoV-2 in hematological patients compared to different control populations. Two independent reviewers screened the literature assessing clinical outcomes of SARS-CoV-2 infection in adult patients with active hematological malignancies published up to June 2021. Primary outcome was COVID-19 related mortality, secondary outcomes were hospital and intensive-care admission, mechanical ventilation, and thromboembolic events. Variables related to study setting, baseline patients' demographic, comorbidities, underlying hematological disease, ongoing chemotherapy, COVID-19 presentation, and treatments were extracted. A total of 67 studies including 10061 hematological patients and 111143 controls were included. Most of the studies were retrospective cohorts (51 studies, 76%) and only 19 (13%) provided data for a control group. A significant increased risk of clinical progression in the hematological population compared to the controls was found in terms of COVID-19 related mortality (OR, 2.12; 95% CI, 1.77- 2.54), hospitalization (OR, 1.98; 95% CI, 1.15 -3.43), intensive-care admission (OR, 1.77; 95% CI, 1.38-2.26), and mechanical ventilation (OR, 2.17; 95% CI, 1.71-2.75). The risk remained significantly higher in the subgroup analysis comparing hematological patients versus solid cancer. Meta-regression analysis of uncontrolled studies showed that older age, male sex, and hypertension were significantly related to worse clinical outcomes of COVID-19 in hematological population. Older age and hypertension were found to be associated also to thromboembolic events. In conclusion, hematological patients have a higher risk of COVID-19 clinical progression compared to both the general population and to patients with solid cancer. This article is protected by copyright. All rights reserved

Salivary glands are a target for SARS- CoV- 2: a source for saliva contamination

The ability of the new coronavirus SARS- CoV- 2 to spread and contaminate is one of the determinants of the COVID- 19 pandemic status. SARS- CoV- 2 has been detected in saliva consistently, with similar sensitivity to that observed in nasopharyngeal swabs. We conducted ultrasound- guided postmortem biopsies in COVID- 19 fatal cases. Samples of salivary glands (SGs; parotid, submandibular, and minor) were obtained. We analyzed samples using RT- qPCR, immunohistochemistry, electron microscopy, and histopathological analysis to identify SARS- CoV- 2 and elucidate qualitative and quantitative viral profiles in salivary glands. The study included 13 female and 11 male patients, with a mean age of 53.12- years (range 8- 83- years). RT- qPCR for SARS- CoV- 2 was positive in 30 SG samples from 18 patients (60% of total SG samples and 75% of all cases). Ultrastructural analyses showed spherical 70- 100- nm viral particles, consistent in size and shape with the Coronaviridae family, in the ductal lining cell cytoplasm, acinar cells, and ductal lumen of SGs. There was also degeneration of organelles in infected cells and the presence of a cluster of nucleocapsids, which suggests viral replication in SG cells. Qualitative histopathological analysis showed morphologic alterations in the duct lining epithelium characterized by cytoplasmic and nuclear vacuolization, as well as nuclear pleomorphism. Acinar cells showed degenerative changes of the zymogen granules and enlarged nuclei. Ductal epithelium and serous acinar cells showed intense expression of ACE2 and TMPRSS receptors. An anti- SARS- CoV- 2 antibody was positive in 8 (53%) of the 15 tested cases in duct lining epithelial cells and acinar cells of major SGs. Only two minor salivary glands were positive for SARS- CoV- 2 by immunohistochemistry. Salivary glands are a reservoir for SARS- CoV- 2 and provide a pathophysiological background for studies that indicate the use of saliva as a diagnostic method for COVID- 19 and highlight this biological fluid’s role in spreading the disease. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168288/1/path5679_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168288/2/path5679.pd

Salivary glands are a target for SARS‐CoV‐2: a source for saliva contamination

The ability of the new coronavirus SARS- CoV- 2 to spread and contaminate is one of the determinants of the COVID- 19 pandemic status. SARS- CoV- 2 has been detected in saliva consistently, with similar sensitivity to that observed in nasopharyngeal swabs. We conducted ultrasound- guided postmortem biopsies in COVID- 19 fatal cases. Samples of salivary glands (SGs; parotid, submandibular, and minor) were obtained. We analyzed samples using RT- qPCR, immunohistochemistry, electron microscopy, and histopathological analysis to identify SARS- CoV- 2 and elucidate qualitative and quantitative viral profiles in salivary glands. The study included 13 female and 11 male patients, with a mean age of 53.12- years (range 8- 83- years). RT- qPCR for SARS- CoV- 2 was positive in 30 SG samples from 18 patients (60% of total SG samples and 75% of all cases). Ultrastructural analyses showed spherical 70- 100- nm viral particles, consistent in size and shape with the Coronaviridae family, in the ductal lining cell cytoplasm, acinar cells, and ductal lumen of SGs. There was also degeneration of organelles in infected cells and the presence of a cluster of nucleocapsids, which suggests viral replication in SG cells. Qualitative histopathological analysis showed morphologic alterations in the duct lining epithelium characterized by cytoplasmic and nuclear vacuolization, as well as nuclear pleomorphism. Acinar cells showed degenerative changes of the zymogen granules and enlarged nuclei. Ductal epithelium and serous acinar cells showed intense expression of ACE2 and TMPRSS receptors. An anti- SARS- CoV- 2 antibody was positive in 8 (53%) of the 15 tested cases in duct lining epithelial cells and acinar cells of major SGs. Only two minor salivary glands were positive for SARS- CoV- 2 by immunohistochemistry. Salivary glands are a reservoir for SARS- CoV- 2 and provide a pathophysiological background for studies that indicate the use of saliva as a diagnostic method for COVID- 19 and highlight this biological fluid’s role in spreading the disease. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168288/1/path5679_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168288/2/path5679.pd