Background A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. Methods This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0•5 mL intramuscular doses of SCB-2019 (30 µg, adjuvanted with 1•50 mg CpG-1018 and 0•75 mg alum) or placebo (0•9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395). Findings 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44•4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67•2% (95•72% CI 54•3-76•8), 83•7% (97•86% CI 55•9-95•4) against moderateto-severe COVID-19, and 100% (97•86% CI 25•3-100•0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78•7% (95% CI 57•3-90•4) for delta, 91•8% (44•9-99•8) for gamma, and 58•6% (13•3-81•5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35•7% [287 of 803] vs 10•3% [81 of 786]) and second (26•9% [189 of 702] vs 7•4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups. Interpretation Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant. Funding Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.

OBJECTIVES:Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to investigate the relationships of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 serum concentrations with the extent of coronary lesions.METHODS:Seventy-four individuals who were undergoing coronary angiography for the first time for diagnostic purposes were enrolled in this study. The extent of the coronary lesion was assessed using the Friesinger Index, and subjects were classified into four groups: no lesions, minor lesions, intermediate lesions and major lesions. Serum biochemical parameters and serum concentrations of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 were analyzed.RESULTS:The vascular cell adhesion molecule-1 concentration was higher than 876 ng/mL in individuals with intermediate and major lesions (p<0.001 and p=0.020, respectively). Moreover, logistic regression analysis showed that these patients had an increased risk of having an intermediate lesion (p=0.007). Interestingly, all individuals with major lesions had vascular cell adhesion molecule-1 concentrations higher than 876 ng/mL. No association was found between the concentrations of the other proteins and the Friesinger Index.CONCLUSIONS:Serum vascular cell adhesion molecule-1 may be associated with the extent of coronary lesions. Moreover, it may represent an alternative to improve the cardiovascular risk classification in patients without acute coronary syndrome.

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in women worldwide. Especially for women, traditional risk factors fail to explain most cases, deaths, and disability-adjusted life years (DALYs) from CVD. Risk factors inherent to the female sex and psychosocial aspects play an essential role in the development of CVD in women. Efforts need to be made to narrow the gap in diagnosis and treatment among women, especially younger ones, among whom CVD prevalence is increasing worldwide. 1 Ischemic heart disease (IHD) remains a major threat to public health, and the overall burden is increasing globally. The GBD 2019 Study estimated 126.5 (95% UI, 118.6-134.7) million prevalent cases of IHD in 2019 globally. Agestandardized rates for DALYs, deaths, and prevalent cases declined from 1990 to 2019, probably due to population growth and aging. 2 In addition, IHD was the leading cause of death and DALYs in Brazil in 2019 for both males (12.22% of total death -95% UI, 11.5%-12.77%; annual percent change -0.022) and females (12.03% of total death -95% UI, 10.66%-12.88%; annual percent change 0.07). It is important to note that there has been an increase in the annual percent change in mortality from IHD in women in recent years (Figure 1). 3 The GBD 2017 estimated 1736 (95% UI, 1689-1779) DALYs lost per 100 000 individuals due to IHD, with lower rates for females (1127; 95% UI, 1084-1163) than for males (2153; 95% UI, 2067-2216), in 2017 in Brazil. From 1990 to 2017, there was a decline in DALYs lost for both males (-47%) and females (-52%) in all Brazilian Federative Units (Figure 2). 4In addition, the GBD 2017 estimated 84 events of IHD per 100 000 inhabitants in 2017 in Brazil. The age-standardized incidence was 104 per 100 000 inhabitants for males and 58 per 100 000 for females. 4 The GBD 2017 estimated a prevalence of IHD in 2017 of 2229 (95% UI, 2098-2372) and 1008 (95% UI, 938-1081) per 100 000 inhabitants for males and females, respectively. The IHD prevalence increased in both sexes from 1990 to 2017 (Figure 3). 4 Mortality due to myocardial infarctionMyocardial infarction (MI) is the leading cause of death in Brazil nowadays. The MI mortality rate decreased between 1996 and 2019, in both sexes, especially among females, being more relevant in the state capitals than in the inner areas. 4 According to the Brazilian Unified Health System (SUS) Department of Information Technology (DATASUS), there were 142 982 hospital admissions for MI in 2018, with inhospital mortality of 11%. In 2018, the DATASUS registered 10 811 primary angioplasties for MI, with in-hospital mortality of 6.3% and a mean length of hospital stay of 5.1 days. In 2018, the total amount reimbursed for coronary

Fundamento: A COVID-19 adicionou um fardo enorme sobre os médicos ao redor do mundo, especialmente as mulheres médicas, que são afetadas pelo aumento da carga de trabalho e pela perda da qualidade de vida. Objetivo: Avaliar os efeitos da pandemia de COVID-19 na qualidade de vida, burnout e espiritualidade de médicas brasileiras que atendem pacientes com COVID-19 direta ou indiretamente. Método: Estudo prospectivo, observacional realizado de 28 de julho a 27 de setembro de 2020, no Brasil, com mulheres médicas de 47 especialidades, a mais frequente sendo a cardiologia (22,8%), sem restrição de idade. Elas responderam voluntariamente um questionário online com questões sobre características demográficas e socioeconômicas, qualidade de vida (WHOQOLbrief) e espiritualidade (WHOQOL-SRPB) e enunciados do Oldenburg Burnout Inventory. A análise estatística utilizou o software R, regressão beta, árvores de classificação e matriz de correlação policórica, com nível de significância de 5%. Resultados: Das 769 respondentes, 61,6% relataram sinais de burnout. Cerca de 64% relataram perda salarial de até 50% durante a pandemia. Algumas relataram falta de energia para as tarefas diárias, sentimentos negativos frequentes, insatisfação com a capacidade para o trabalho, e que cuidar de outras pessoas não agregava sentido às suas vidas. Os sentimentos negativos correlacionaram-se negativamente com a satisfação com a vida sexual, a satisfação com as relações pessoais e a energia para as tarefas diárias. A incapacidade de permanecer otimista em tempos de incerteza correlacionou-se positivamente com a sensação de insegurança no dia a dia e com o não reconhecimento de que cuidar de outras pessoas trouxesse sentido à vida. Conclusão: O presente estudo mostrou uma alta frequência de burnout entre as médicas brasileiras que responderam ao questionário durante a pandemia de COVID-19. Apesar disso, apresentavam uma qualidade de vida relativamente boa e acreditavam que a espiritualidade trazia-lhes conforto e segurança nos momentos difíceis. Palavras-chave: Mulheres Médicas; Burnout; Pandemia de COVID-19; Brasil.

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