Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

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

Fazer a história do ensino das línguas e das civilizações estrangeiras no ensino superior francês no século XX

La enseñanza de lengua y literatura extranjeras en la enseñanza superior francesa, en la época contemporánea, sólo fue objeto de un número restricto de trabajos. Este artículo se propone, a partir del caso del germanismo, trazar la historia de estas disciplinas desde su aparición dentro de la universidad alrededor de 1830 hasta la época posterior a la reforma de 1968. Tres grandes etapas aparecen, en un proceso continuo de construcción disciplinar: un período de indeterminación, de los años 1830 a los años 1880, durante lo cual se habla de lenguas extranjeras en general; un período de especialización, en la virada del siglo, con la aparición de las cátedras de estudios alemanes, italianos y, en fin, en la mitad del siglo XX, un movimiento de respetabilidad que visa elevar estas disciplinas dentro de la jerarquía universitaria.O ensino de língua e literatura estrangeiras no ensino superior francês, na época contemporânea, só foi o objeto de um número restrito de trabalhos. Este artigo se propõe, a partir do caso do germanismo, traçar a história destas disciplinas desde sua aparição dentro da universidade por volta de 1830 até à época posterior à reforma de 1968. Três grandes etapas aparecem, em um processo contínuo de construção disciplinar: um período de indeterminação, dos anos 1830 aos anos 1880, durante o qual se fala de línguas estrangeiras em geral; um período de especialização, na virada do século, com a aparição das cadeiras de estudos alemães, italianos e, enfim, na metade do século XX, um movimento de respeitabilidade que visa elevar estas disciplinas dentro da hierarquia universitária.In contemporary period, the study of language and foreign literature teaching in French Universities was the target of a reduced number of works. Since the Germanist case, this article intends to describe these disciplines’histories up to their University introduction around 1830, until the period after the 1968 University Reform. Three big stages of constant process of disciplinary organization appear: an undeterminated process, from the 1830’s to the 1880’s, when we talk about foreign languages in general; an specialization period, at the century turning, with Germain, Italian disciplines and studies. Finally, in the middle 20th century, a respectfulness movement which proposes to elevate these disciplines within academic hierarchy take place

Um modelo de escola na França em torno de 1660-1740: a escola cristã

In the second half of seventeenth century, the Catholic Church helps to build a Christian school model in France: a school against society disorder. This text underlines how school organization, teaching methods, imposed gestures, life habits, and subjects taught contribute to the purpose of instructing poor children.A Igreja ajuda a construir um modelo de escola cristã, na segunda metade do século XVII, na França: uma escola contra a desordem da sociedade. Este texto destaca como a organização da escola, a maneira de ensinar, os gestos e hábitos de vidas impostos, e os conteúdos de ensino, participam para essa finalidade de instrução das crianças pobres.La Iglesia ayuda a construir un modelo de escuela cristiana, en la segunda mitad del siglo XVII, en Francia: una escuela contra el desorden de la sociedad. Este texto destaca como la organización de la escuela, la manera de enseñar, los gestos y hábitos de vidas impuestos, y los contenidos de enseñanza, participan para esa finalidad de instrucción de los niños pobres

Fazer a história do ensino das línguas e das civilizações estrangeiras no ensino superior francês no século XX - Historicizing language and foreign: civilization teaching in french universities in the 20th century

Resumo O ensino de língua e literatura estrangeiras no ensino superior francês, na época contemporânea, só foi o objeto de um número restrito de trabalhos. Este artigo se propõe, a partir do caso do germanismo, traçar a história destas disciplinas desde sua aparição dentro da universidade por volta de 1830 até à época posterior à reforma de 1968. Três grandes etapas aparecem, em um processo contínuo de construção disciplinar: um período de indeterminação, dos anos 1830 aos anos 1880, durante o qual se fala de línguas estrangeiras em geral; um período de especialização, na virada do século, com a aparição das cadeiras de estudos alemães, italianos e, enfim, na metade do século XX, um movimento de respeitabilidade que visa elevar estas disciplinas dentro da hierarquia universitária. Palavras-chave: ensino superior; línguas estrangeiras; França; época contemporânea.   HISTORICIZING LANGUAGE AND FOREIGN: CIVILIZATION TEACHING IN FRENCH UNIVERSITIES IN THE 20TH CENTURY Abstract In contemporary period, the study of language and foreign literature teaching in French Universities was the target of a reduced number of works. Since the Germanist case, this article intends to describe these disciplines’histories up to their University introduction around 1830, until the period after the 1968 University Reform. Three big stages of constant process of disciplinary organization appear: an undeterminated process, from the 1830’s to the 1880’s, when we talk about foreign languages in general; an specialization period, at the century turning, with Germain, Italian disciplines and studies. Finally, in the middle 20th century, a respectfulness movement which proposes to elevate these disciplines within academic hierarchy take place. Keywords: further education; foreign languages; France; contemporary.   HACER LA HISTORIA DE LA ENSEÑANZA DE LAS LENGUAS Y DE LAS CIVILIZACIONES EXTRANJERAS EN LA ENSEÑANZA SUPERIOR FRANCESA EN EL SIGLO XX Resumen La enseñanza de lengua y literatura extranjeras en la enseñanza superior francesa, en la época contemporánea, sólo fue objeto de un número restricto de trabajos. Este artículo se propone, a partir del caso del germanismo, trazar la historia de estas disciplinas desde su aparición dentro de la universidad alrededor de 1830 hasta la época posterior a la reforma de 1968. Tres grandes etapas aparecen, en un proceso continuo de construcción disciplinar: un período de indeterminación, de los años 1830 a los años 1880, durante lo cual se habla de lenguas extranjeras en general; un período de especialización, en la virada del siglo, con la aparición de las cátedras de estudios alemanes, italianos y, en fin, en la mitad del siglo XX, un movimiento de respetabilidad que visa elevar estas disciplinas dentro de la jerarquía universitaria. Palabras-clave: enseñanza superior; lenguas extranjeras; Francia; época contemporánea

Um modelo de escola na França em torno de 1660-1740: a escola cristã - A school model in France around 1660-1740: the christian school

Resumo A Igreja ajuda a construir um modelo de escola cristã, na segunda metade do século XVII, na França: uma escola contra a desordem da sociedade. Este texto destaca como a organização da escola, a maneira de ensinar, os gestos e hábitos de vidas impostos, e os conteúdos de ensino, participam para essa finalidade de instrução das crianças pobres. Palavras-chave: regulação social, religião, maneira de ensinar, ordem do tempo, habitus, conteúdo de ensino.   A SCHOOL MODEL IN FRANCE AROUND 1660-1740: THE CHRISTIAN SCHOOL Abstract In the second half of seventeenth century, the Catholic Church helps to build a Christian school model in France: a school against society disorder. This text underlines how school organization, teaching methods, imposed gestures, life habits, and subjects taught contribute to the purpose of instructing poor children. Keywords: social regulation, religion, teaching methods, time ordering, habitus, teaching contents.   UN MODELO DE ESCUELA EN FRANCIA ALREDEDOR DE 1660-1740: LA ESCUELA CRISTIANA Resumen La Iglesia ayuda a construir un modelo de escuela cristiana, en la segunda mitad del siglo XVII, en Francia: una escuela contra el desorden de la sociedad. Este texto destaca como la organización de la escuela, la manera de enseñar, los gestos y hábitos de vidas impuestos, y los contenidos de enseñanza, participan para esa finalidad de instrucción de los niños pobres. Palabras-clave: regulación social, religión, manera de enseñar, orden del tiempo, habitus, contenido de enseñanza