Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci.

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10-8) and suggestive (p < 1 × 10-6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

Geographic inequalities in health intervention coverage - mapping the composite coverage index in Peru using geospatial modelling.

BACKGROUND: The composite coverage index (CCI) provides an integrated perspective towards universal health coverage in the context of reproductive, maternal, newborn and child health. Given the sample design of most household surveys does not provide coverage estimates below the first administrative level, approaches for achieving more granular estimates are needed. We used a model-based geostatistical approach to estimate the CCI at multiple resolutions in Peru. METHODS: We generated estimates for the eight indicators on which the CCI is based for the departments, provinces, and areas of 5 × 5 km of Peru using data from two national household surveys carried out in 2018 and 2019 plus geospatial covariates. Bayesian geostatistical models were fit using the INLA-SPDE approach. We assessed model fit using cross-validation at the survey cluster level and by comparing modelled and direct survey estimates at the department-level. RESULTS: CCI coverage in the provinces along the coast was consistently higher than in the remainder of the country. Jungle areas in the north and east presented the lowest coverage levels and the largest gaps between and within provinces. The greatest inequalities were found, unsurprisingly, in the largest provinces where populations are scattered in jungle territory and are difficult to reach. CONCLUSIONS: Our study highlighted provinces with high levels of inequality in CCI coverage indicating areas, mostly low-populated jungle areas, where more attention is needed. We also uncovered other areas, such as the border with Bolivia, where coverage is lower than the coastal provinces and should receive increased efforts. More generally, our results make the case for high-resolution estimates to unveil geographic inequities otherwise hidden by the usual levels of survey representativeness.

Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention.

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

[Mask use during the COVID-19 pandemic in Brazil: results of the EPICOVID19-BR study]. / Uso de máscara durante a pandemia de COVID-19 no Brasil: resultados do estudo EPICOVID19-BR.

By March 3, 2022, the COVID-19 pandemic has caused more than 399 million infections and claimed the lives of more than five million people worldwide. To reduce infection rates, a series of prevention measures indicated by the World Health Organization (WHO) were adopted by countries, including the use of masks. This study aims to describe mask use in Brazil via data analysis from the EPICOVID19-BR, a population-based study conducted in 133 cities in the country in four phases between March and August 2020. The proportion of individuals who reported wearing a mask when they left their homes was 97.9% (95%CI: 97.8-98.0). The interviewer did not see interviewees' mask in 50% (95%CI: 49.9-51.1) of the cases at the time of the interview. However, between phase one and four of the survey, we observed a 4.4% decrease in the proportion of interviewees who failed to wear masks at the time of the interview. Mask non-visualization was more prominent in women, participants aged 10-19 and 20-29 years of indigenous, black, and brown skin color, and those with elementary and high school education and in the Central-West Region. The use of cloth masks showed a 91.4% predominance (95%CI: 91.2-1.5) with a 4.9% increase between phases 1 and 4. The results of the study bring important information to reinforce COVID-19 control policies in Brazil. The high percentage of people who failed to wear masks at the time of the interview suggests that it is still important to reinforce prevention and self-care, rather than relating mask wear to a mandatory measure.

A pandemia de COVID-19 já causou mais de 399 milhões de infecções e custou a vida de mais de cinco milhões de pessoas no mundo, até 3 de março de 2022. Para reduzir a taxa de infecção, uma série de medidas de prevenção indicadas pela Organização Mundial da Saúde (OMS) foram adotadas pelos países, entre elas, o uso de máscara. O objetivo deste estudo é descrever a utilização de máscara na população brasileira, através da análise de dados do EPICOVID19-BR, um estudo de base populacional realizado em 133 cidades do país, em quatro fases entre março e agosto de 2020. A proporção de indivíduos que preferiram usar máscara quando saíam de casa foi de 97,9% (IC95%: 97,8-98,0). O entrevistador não visualizou a máscara do entrevistado em 50% (IC95%: 49,9-51,1) dos casos no momento da entrevista, no entanto, entre a fase uma e quatro da pesquisa, observou-se uma diminuição de 4,4 pontos percentuais na proporção de entrevistados que não usaram máscara no momento da entrevista. A não visualização da máscara foi mais observada em mulheres, participantes com idade entre 10-19 e 20-29 anos, de cor de pele indígena, preta, e parda, entre as pessoas com Ensinos Fundamental e Médio e na Região Centro-oeste. O uso de máscara de tecido foi predominante 91,4% (IC95%: 91,2-91,5) com um aumento de 4,9 pontos percentuais entre as fases 1 e 4. Os resultados do estudo trazem informações importantes para reforçar as políticas de controle de COVID-19 no Brasil. O alto percentual de pessoas sem máscara na hora da entrevista sugere que ainda é importante reforçar o aspecto preventivo e de autocuidado, não fazendo do uso da máscara algo apenas ligado à obrigatoriedade.

La pandemia del COVID-19 ha provocado más de 399 millones de infecciones y se ha cobrado la vida de más de cinco millones de personas en todo el mundo hasta el 3 de Marzo de 2022. Para reducir la tasa de contagios, los países adoptaron una serie de medidas de prevención indicadas por la Organización Mundial de la Salud (OMS), entre ellas el uso de mascarillas. El objetivo de este estudio es describir el uso de mascarillas en la población brasileña, utilizando el análisis de datos de EPICOVID19-BR, un estudio de base poblacional realizado en 133 ciudades del país, en cuatro fases entre marzo y agosto de 2020. La proporción de personas que informaron usar mascarillas al salir de casa fue del 97,9% (IC95%: 97,8-98,0). El entrevistador no vio la mascarilla del entrevistado en el 50% (IC95%: 49,9-51,1) de los casos al momento de la entrevista, sin embargo entre las fases uno y cuatro de la investigación se observó una disminución de 4,4 puntos porcentuales en la proporción de los encuestados que no llevaban mascarilla durante la entrevista. Se observó una mayor visualización de falta de uso de mascarillas en las mujeres, en participantes con edades entre 10-19 y 20-29 años, de color de piel indígena, negra y parda, entre personas con educación primaria y secundaria y en la Región Centro-oeste. Hubo un mayor predominio de uso de mascarillas de tela en el 91,4% (IC95%: 91,2-91,5) con un aumento de 4,9 puntos porcentuales entre las fases 1 y 4. Los resultados muestran la importancia de fortalecer las políticas de prevención del COVID-19 en Brasil. El alto porcentaje de personas sin mascarilla al momento de la entrevista sugiere que es importante reforzar la prevención y el autocuidado en general no solo relacionado a la obligatoriedad en el uso de mascarillas.

COVID-19 and outpatient care: a nationwide household survey.

We aimed to assess the proportion of the population in 133 Brazilian municipalities who - from March to August 2020 - had a health problem but failed to seek care or failed to attend to a health service for routine appointment or examination. We conducted a household survey from August 24-27 in 133 Brazilian cities by asking the subjects if, since the beginning of the COVID-19 pandemic in March 2020, they had suffered from a health problem but did not seek care or failed to attend to a routine or screening examination. Poisson regression was used for the analyses. We interviewed 33,250 subjects and 11.8% (95%CI: 11.4-12.1) reported that, since March 2020, they failed to seek care despite being ill, 17.3% (95%CI: 16.9-17.7) failed to attend to a routine or screening examination and 23.9% (95%CI: 23.4-24.4) reported one or both outcomes. Health service closure and fear of the COVID-19 infection were the main reasons for not seeking care. Women and the poorest were more likely to not look for a health service, despite having a health problem or a scheduled routine appointment. On the other hand, those subjects who self-identified as white were less likely to not look for a health service. The COVID-19 pandemic is more critical for the indigenous people and the poorest, and these people are also more likely to not seek care for other health conditions during the pandemic.

Effects of early-life poverty on health and human capital in children and adolescents: analyses of national surveys and birth cohort studies in LMICs.

The survival and nutrition of children and, to a lesser extent, adolescents have improved substantially in the past two decades. Improvements have been linked to the delivery of effective biomedical, behavioural, and environmental interventions; however, large disparities exist between and within countries. Using data from 95 national surveys in low-income and middle-income countries (LMICs), we analyse how strongly the health, nutrition, and cognitive development of children and adolescents are related to early-life poverty. Additionally, using data from six large, long-running birth cohorts in LMICs, we show how early-life poverty can have a lasting effect on health and human capital throughout the life course. We emphasise the importance of implementing multisectoral anti-poverty policies and programmes to complement specific health and nutrition interventions delivered at an individual level, particularly at a time when COVID-19 continues to disrupt economic, health, and educational gains achieved in the recent past.

Health and development from preconception to 20 years of age and human capital.

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5-19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood.

COVID-19 and outpatient care: a nationwide household survey / COVID-19 e assistência ambulatorial: uma pesquisa domiciliar de abrangência nacional / COVID-19 y atención ambulatoria: una encuesta domiciliaria a escala nacional

We aimed to assess the proportion of the population in 133 Brazilian municipalities who - from March to August 2020 - had a health problem but failed to seek care or failed to attend to a health service for routine appointment or examination. We conducted a household survey from August 24-27 in 133 Brazilian cities by asking the subjects if, since the beginning of the COVID-19 pandemic in March 2020, they had suffered from a health problem but did not seek care or failed to attend to a routine or screening examination. Poisson regression was used for the analyses. We interviewed 33,250 subjects and 11.8% (95%CI: 11.4-12.1) reported that, since March 2020, they failed to seek care despite being ill, 17.3% (95%CI: 16.9-17.7) failed to attend to a routine or screening examination and 23.9% (95%CI: 23.4-24.4) reported one or both outcomes. Health service closure and fear of the COVID-19 infection were the main reasons for not seeking care. Women and the poorest were more likely to not look for a health service, despite having a health problem or a scheduled routine appointment. On the other hand, those subjects who self-identified as white were less likely to not look for a health service. The COVID-19 pandemic is more critical for the indigenous people and the poorest, and these people are also more likely to not seek care for other health conditions during the pandemic.

O estudo teve como objetivo avaliar a proporção da população de 133 cidades brasileiras que apresentou algum problema de saúde entre março e agosto de 2020, mas que deixou de procurar atendimento, ou que deixou de buscar um serviço de saúde para consultas ou exames de rotina. Foram realizadas entrevistas domiciliares entre 24 e 27 de agosto de 2020 em 133 áreas urbanas brasileiras. Perguntava-se aos indivíduos se, desde o início da pandemia de COVID-19 em março de 2020, haviam sofrido algum problema de saúde mais não haviam procurado atendimento, ou se haviam deixado de realizar consultas ou exames de rotina. A regressão de Poisson foi utilizada para as análises. Foram entrevistados 33.250 indivíduos, entre os quais 11,8% (IC95%: 11,4-12,1) relataram que desde março de 2020 haviam deixado de procurar atendimento apesar de estarem doentes, 17,3% (IC95%: 16,9-17,7) haviam deixado de comparecer a consultas de rotina ou triagem e 23,9% (IC95%: 23,4-24,4) relataram um ou ambos os desfechos. O fechamento dos serviços de saúde e o medo da infecção pelo SARS-CoV-2 foram os principais motivos para não buscar atendimento. As mulheres e os indivíduos com menor nível socioeconômico mostraram maior probabilidade de não procurarem serviços de saúde em caso de doença, ou de faltar a consultas de rotina previamente agendadas. Por outro lado, indivíduos que se identificavam como brancos eram menos propensos a deixar de procurar os serviços de saúde. A pandemia da COVID-19 está afetando mais duramente os indígenas e as pessoas com menor nível socioeconômico, que também são mais propensos a deixar de procurar atendimento para outras condições de saúde durante a pandemia.

Se realizó un estudio con el fin de evaluar la proporción de población en 133 ciudades brasileñas que -de marzo a agosto 2020- tuvieron un problema de salud, pero no consiguieron buscar cuidados, o presentarse en un servicio de salud para consultas de rutina o exámenes. Se llevó a cabo una encuesta domiciliaria entre el 24 y 27 de agosto en 133 áreas urbanas brasileñas. A los encuestados se les preguntó si, desde el principio de la pandemia de COVID-19 en marzo de 2020, habían sufrido algún problema de salud, pero no habían buscado asistencia, o no consiguieron presentarse a exámenes de rutina o de exploración. Se utilizó una regresión de Poisson para los análisis. Se entrevistó a 33.250 individuos, y un 11,8% (IC95%: 11,4-12,1) informaron que desde marzo de 2020 no consiguieron buscar asistencia, a pesar de estar enfermos, un 17,3% (IC95%: 16,9-17,7) no consiguieron presentarse a exámenes de rutina o visitas de exploración, y un 23,9% (IC95%: 23,4-24,4) informaron de uno o ambos resultados. El cierre de los servicios de salud y el miedo a contraer COVID-19 fueron las razones principales para no buscar cuidados. Las mujeres y aquellos que tenían un estatus socioeconómico bajo eran más propensos a no buscar asistencia sanitaria, tanto si tenían un problema médico, como para un chequeo rutinario o se saltaban una cita médica programada. Por otro lado, estas personas que se autoidentificaron como blancas eran menos propensas a no buscar asistencia sanitaria. La pandemia de COVID-19 está golpeando duramente a los indígenas y a quienes tienen un estatus socioeconómico bajo, y estas personas también son más propensas a no conseguir buscar asistencia sanitaria relacionada con otros problemas de salud durante la pandemia.

Uso de máscara durante a pandemia de COVID-19 no Brasil: resultados do estudo EPICOVID19-BR / Mask use during the COVID-19 pandemic in Brazil: results of the EPICOVID19-BR study / Uso de mascarillas durante la pandemia de COVID-19 en Brasil: resultados del estudio EPICOVID19-BR

A pandemia de COVID-19 já causou mais de 399 milhões de infecções e custou a vida de mais de cinco milhões de pessoas no mundo, até 3 de março de 2022. Para reduzir a taxa de infecção, uma série de medidas de prevenção indicadas pela Organização Mundial da Saúde (OMS) foram adotadas pelos países, entre elas, o uso de máscara. O objetivo deste estudo é descrever a utilização de máscara na população brasileira, através da análise de dados do EPICOVID19-BR, um estudo de base populacional realizado em 133 cidades do país, em quatro fases entre março e agosto de 2020. A proporção de indivíduos que preferiram usar máscara quando saíam de casa foi de 97,9% (IC95%: 97,8-98,0). O entrevistador não visualizou a máscara do entrevistado em 50% (IC95%: 49,9-51,1) dos casos no momento da entrevista, no entanto, entre a fase uma e quatro da pesquisa, observou-se uma diminuição de 4,4 pontos percentuais na proporção de entrevistados que não usaram máscara no momento da entrevista. A não visualização da máscara foi mais observada em mulheres, participantes com idade entre 10-19 e 20-29 anos, de cor de pele indígena, preta, e parda, entre as pessoas com Ensinos Fundamental e Médio e na Região Centro-oeste. O uso de máscara de tecido foi predominante 91,4% (IC95%: 91,2-91,5) com um aumento de 4,9 pontos percentuais entre as fases 1 e 4. Os resultados do estudo trazem informações importantes para reforçar as políticas de controle de COVID-19 no Brasil. O alto percentual de pessoas sem máscara na hora da entrevista sugere que ainda é importante reforçar o aspecto preventivo e de autocuidado, não fazendo do uso da máscara algo apenas ligado à obrigatoriedade.

By March 3, 2022, the COVID-19 pandemic has caused more than 399 million infections and claimed the lives of more than five million people worldwide. To reduce infection rates, a series of prevention measures indicated by the World Health Organization (WHO) were adopted by countries, including the use of masks. This study aims to describe mask use in Brazil via data analysis from the EPICOVID19-BR, a population-based study conducted in 133 cities in the country in four phases between March and August 2020. The proportion of individuals who reported wearing a mask when they left their homes was 97.9% (95%CI: 97.8-98.0). The interviewer did not see interviewees' mask in 50% (95%CI: 49.9-51.1) of the cases at the time of the interview. However, between phase one and four of the survey, we observed a 4.4% decrease in the proportion of interviewees who failed to wear masks at the time of the interview. Mask non-visualization was more prominent in women, participants aged 10-19 and 20-29 years of indigenous, black, and brown skin color, and those with elementary and high school education and in the Central-West Region. The use of cloth masks showed a 91.4% predominance (95%CI: 91.2-1.5) with a 4.9% increase between phases 1 and 4. The results of the study bring important information to reinforce COVID-19 control policies in Brazil. The high percentage of people who failed to wear masks at the time of the interview suggests that it is still important to reinforce prevention and self-care, rather than relating mask wear to a mandatory measure.

La pandemia del COVID-19 ha provocado más de 399 millones de infecciones y se ha cobrado la vida de más de cinco millones de personas en todo el mundo hasta el 3 de Marzo de 2022. Para reducir la tasa de contagios, los países adoptaron una serie de medidas de prevención indicadas por la Organización Mundial de la Salud (OMS), entre ellas el uso de mascarillas. El objetivo de este estudio es describir el uso de mascarillas en la población brasileña, utilizando el análisis de datos de EPICOVID19-BR, un estudio de base poblacional realizado en 133 ciudades del país, en cuatro fases entre marzo y agosto de 2020. La proporción de personas que informaron usar mascarillas al salir de casa fue del 97,9% (IC95%: 97,8-98,0). El entrevistador no vio la mascarilla del entrevistado en el 50% (IC95%: 49,9-51,1) de los casos al momento de la entrevista, sin embargo entre las fases uno y cuatro de la investigación se observó una disminución de 4,4 puntos porcentuales en la proporción de los encuestados que no llevaban mascarilla durante la entrevista. Se observó una mayor visualización de falta de uso de mascarillas en las mujeres, en participantes con edades entre 10-19 y 20-29 años, de color de piel indígena, negra y parda, entre personas con educación primaria y secundaria y en la Región Centro-oeste. Hubo un mayor predominio de uso de mascarillas de tela en el 91,4% (IC95%: 91,2-91,5) con un aumento de 4,9 puntos porcentuales entre las fases 1 y 4. Los resultados muestran la importancia de fortalecer las políticas de prevención del COVID-19 en Brasil. El alto porcentaje de personas sin mascarilla al momento de la entrevista sugiere que es importante reforzar la prevención y el autocuidado en general no solo relacionado a la obligatoriedad en el uso de mascarillas.

Population-level seropositivity trend for SARS-Cov-2 in Rio Grande do Sul, Brazil.

OBJECTIVE: To describe the evolution of seropositivity in the State of Rio Grande do Sul, Brazil, through 10 consecutive surveys conducted between April 2020 and April 2021. METHODS: Nine cities covering all regions of the State were studied, 500 households in each city. One resident in each household was randomly selected for testing. In survey rounds 1-8 we used the rapid WONDFO SARS-CoV-2 Antibody Test (Wondfo Biotech Co., Guangzhou, China). In rounds 9-10, we used a direct ELISA test that identifies IgG to the viral S protein (S-UFRJ). In terms of social distancing, individuals were asked three questions, from which we generated an exposure score using principal components analysis. RESULTS: Antibody prevalence in early April 2020 was 0.07%, increasing to 10.0% in February 2021, and to 18.2% in April 2021. In round 10, self-reported whites showed the lowest seroprevalence (17.3%), while indigenous individuals presented the highest (44.4%). Seropositivity increased by 40% when comparing the most with the least exposed. CONCLUSIONS: The proportion of the population already infected by SARS-Cov-2 in the state is still far from any perspective of herd immunity and the infection affects population groups in very different levels.

Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits.

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

Assortative mating and within-spouse pair comparisons.

Spousal comparisons have been proposed as a design that can both reduce confounding and estimate effects of the shared adulthood environment. However, assortative mating, the process by which individuals select phenotypically (dis)similar mates, could distort associations when comparing spouses. We evaluated the use of spousal comparisons, as in the within-spouse pair (WSP) model, for aetiological research such as genetic association studies. We demonstrated that the WSP model can reduce confounding but may be susceptible to collider bias arising from conditioning on assorted spouse pairs. Analyses using UK Biobank spouse pairs found that WSP genetic association estimates were smaller than estimates from random pairs for height, educational attainment, and BMI variants. Within-sibling pair estimates, robust to demographic and parental effects, were also smaller than random pair estimates for height and educational attainment, but not for BMI. WSP models, like other within-family models, may reduce confounding from demographic factors in genetic association estimates, and so could be useful for triangulating evidence across study designs to assess the robustness of findings. However, WSP estimates should be interpreted with caution due to potential collider bias.

[Prevalence of antibodies against SARS-CoV-2 according to socioeconomic and ethnic status in a nationwide Brazilian surveyPrevalência de anticorpos contra o SARS-CoV-2 de acordo com o status socioeconômico e étnico em uma pesquisa nacional no Brasil]. / Prevalencia de anticuerpos contra el SARS-CoV-2 según el estatus socioeconómico y étnico en una encuesta nacional de Brasil.

OBJECTIVES: To investigate socioeconomic and ethnic group inequalities in prevalence of antibodies against SARS-CoV-2 in the 27 federative units of Brazil. METHODS: In this cross-sectional study, three household surveys were carried out on May 14-21, June 4-7, and June 21-24, 2020 in 133 Brazilian urban areas. Multi-stage sampling was used to select 250 individuals in each city to undergo a rapid antibody test. Subjects answered a questionnaire on household assets, schooling and self-reported skin color/ethnicity using the standard Brazilian classification in five categories: white, black, brown, Asian or indigenous. Principal component analyses of assets was used to classify socioeconomic position into five wealth quintiles. Poisson regression was used for the analyses. RESULTS: 25 025 subjects were tested in the first, 31 165 in the second, and 33 207 in the third wave of the survey, with prevalence of positive results equal to 1.4%, 2.4%, and 2.9% respectively. Individuals in the poorest quintile were 2.16 times (95% confidence interval 1.86; 2.51) more likely to test positive than those in the wealthiest quintile, and those with 12 or more years of schooling had lower prevalence than subjects with less education. Indigenous individuals had 4.71 (3.65; 6.08) times higher prevalence than whites, as did those with black or brown skin color. Adjustment for region of the country reduced the prevalence ratios according to wealth, education and ethnicity, but results remained statistically significant. CONCLUSIONS: The prevalence of antibodies against SARS-CoV-2 in Brazil shows steep class and ethnic gradients, with lowest risks among white, educated and wealthy individuals.

OBJETIVOS: Investigar as desigualdades socioeconômicas e étnicas na prevalência de anticorpos contra SARS-CoV-2 nas 27 unidades federativas do Brasil. MÉTODOS: Neste estudo transversal, três pesquisas domiciliares foram realizadas de 14 a 21 de maio, 4 a 7 de junho, e 21-24 de junho, 2020 em 133 áreas urbanas brasileiras. Amostragem em várias etapas foi utilizada para selecionar 250 indivíduos em cada cidade para se submeter a um teste rápido de anticorpos. Os sujeitos responderam a um questionário sobre bens domésticos, escolaridade e cor da pele/etnicidade (auto-relatada utilizando a classificação padrão brasileira de cinco categorias: branco, preto, pardo, asiático ou indígena). A análise dos componentes principais dos ativos foi utilizada para classificar a posição socioeconómica em cinco quintis de riqueza. A regressão de Poisson foi utilizada para as análises. RESULTADOS: 25 025 indivíduos foram testados na primeira pesquisa, 31 165 na segunda, e 33 207 na terceira, com prevalência de resultados positivos de 1,4%, 2,4% e 2,9%, respectivamente. Indivíduos no quintil mais pobre tinham 2,16 vezes (intervalo de confiança de 95% 1,86; 2,51) mais probabilidade de ter um resultado positivo do que aqueles do quintil mais rico, e aqueles com 12 ou mais anos de escolaridade tinham uma prevalência menor do que aqueles com menos educação. Os indivíduos indígenas tinham 4,71 (3,65; 6,08) vezes mais prevalência do que os brancos, assim como aqueles com cor da pele preta ou parda. O ajuste regional reduziu as taxas de prevalência de acordo com a riqueza, educação e etnia, mas os resultados permaneceram estatisticamente significativos. CONCLUSÕES: A prevalência de anticorpos contra a SARS-CoV-2 no Brasil mostra gradientes relacionados com a posição socioeconómica e a etnia muito acentuados, com os menores riscos entre os indivíduos brancos, educados e ricos.

Prevalencia de anticuerpos contra el SARS-CoV-2 según el estatus socioeconómico y étnico en una encuesta nacional de Brasil

[RESUMEN]. Objetivos. Investigar las desigualdades socioeconómicas y entre distintos grupos étnicos en la prevalencia de anticuerpos contra el SARS-CoV-2 en las 27 unidades federativas de Brasil. Métodos. En este estudio transversal, se realizaron tres encuestas de hogares los días 14-21 de mayo, 4-7 de junio y 21-24 de junio de 2020 en 133 áreas urbanas brasileñas. Se utilizó un muestreo de etapas múltiples para seleccionar 250 individuos en cada ciudad a fin de someterlos a una prueba rápida de anticuerpos. Los sujetos respondieron un cuestionario sobre los bienes del hogar, la escolaridad y el color de la piel y etnia (autodeclarado utilizando la clasificación brasileña estándar de cinco categorías: blanco, negro, pardo, asiático o indígena). Se utilizó el análisis de los componentes principales de los bienes para clasificar el estatus socioeconómico en cinco quintiles de riqueza. Se empleó la regresión de Poisson para los análisis. Resultados. Se analizaron 25 025 sujetos en la primera encuesta, 31 165 en la segunda y 33 207 en la tercera, que mostraron una prevalencia de resultados positivos de 1,4%, 2,4% y 2,9%; respectivamente. Los individuos del quintil más pobre tuvieron 2,16 veces más probabilidades de presentar un resultado positivo (intervalo de confianza del 95%: 1,86-2,51) que los del quintil más rico, y los que tenían 12 o más años de escolaridad tuvieron una prevalencia menor que los sujetos con menos educación. Las personas indígenas presentaron una prevalencia 4,71 (IC95%: 3,65-6,08) veces mayor que las blancas, al igual que las de piel negra o parda. El ajuste por región del país redujo los índices de prevalencia según la riqueza, la educación y el origen étnico, pero los resultados siguieron siendo estadísticamente significativos. Conclusiones. La prevalencia de anticuerpos contra el SARS-CoV-2 en Brasil muestra gradientes relacionados con la posición socioeconómica y la etnia muy pronunciados, con menor riesgo en las personas blancas, educadas y ricas.

[ABSTRACT]. Objectives. To investigate socioeconomic and ethnic group inequalities in prevalence of antibodies against SARS-CoV-2 in the 27 federative units of Brazil. Methods. In this cross-sectional study, three household surveys were carried out on May 14-21, June 4-7, and June 21-24, 2020 in 133 Brazilian urban areas. Multi-stage sampling was used to select 250 individuals in each city to undergo a rapid antibody test. Subjects answered a questionnaire on household assets, schooling and self-reported skin color/ethnicity using the standard Brazilian classification in five categories: white, black, brown, Asian or indigenous. Principal component analyses of assets was used to classify socioeconomic position into five wealth quintiles. Poisson regression was used for the analyses. Results. 25 025 subjects were tested in the first, 31 165 in the second, and 33 207 in the third wave of the survey, with prevalence of positive results equal to 1.4%, 2.4%, and 2.9% respectively. Individuals in the poorest quintile were 2.16 times (95% confidence interval 1.86; 2.51) more likely to test positive than those in the wealthiest quintile, and those with 12 or more years of schooling had lower prevalence than subjects with less education. Indigenous individuals had 4.71 (3.65; 6.08) times higher prevalence than whites, as did those with black or brown skin color. Adjustment for region of the country reduced the prevalence ratios according to wealth, education and ethnicity, but results remained statistically significant. Conclusions. The prevalence of antibodies against SARS-CoV-2 in Brazil shows steep class and ethnic gradients, with lowest risks among white, educated and wealthy individuals.

[RESUMO]. Objetivos. Investigar as desigualdades socioeconômicas e étnicas na prevalência de anticorpos contra SARS-CoV-2 nas 27 unidades federativas do Brasil. Métodos. Neste estudo transversal, três pesquisas domiciliares foram realizadas de 14 a 21 de maio, 4 a 7 de junho, e 21-24 de junho, 2020 em 133 áreas urbanas brasileiras. Amostragem em várias etapas foi utilizada para selecionar 250 indivíduos em cada cidade para se submeter a um teste rápido de anticorpos. Os sujeitos responderam a um questionário sobre bens domésticos, escolaridade e cor da pele/etnicidade (auto-relatada utilizando a classificação padrão brasileira de cinco categorias: branco, preto, pardo, asiático ou indígena). A análise dos componentes principais dos ativos foi utilizada para classificar a posição socioeconómica em cinco quintis de riqueza. A regressão de Poisson foi utilizada para as análises. Resultados. 25 025 indivíduos foram testados na primeira pesquisa, 31 165 na segunda, e 33 207 na terceira, com prevalência de resultados positivos de 1,4%, 2,4% e 2,9%, respectivamente. Indivíduos no quintil mais pobre tinham 2,16 vezes (intervalo de confiança de 95% 1,86; 2,51) mais probabilidade de ter um resultado positivo do que aqueles do quintil mais rico, e aqueles com 12 ou mais anos de escolaridade tinham uma prevalência menor do que aqueles com menos educação. Os indivíduos indígenas tinham 4,71 (3,65; 6,08) vezes mais prevalência do que os brancos, assim como aqueles com cor da pele preta ou parda. O ajuste regional reduziu as taxas de prevalência de acordo com a riqueza, educação e etnia, mas os resultados permaneceram estatisticamente significativos. Conclusões. A prevalência de anticorpos contra a SARS-CoV-2 no Brasil mostra gradientes relacionados com a posição socioeconómica e a etnia muito acentuados, com os menores riscos entre os indivíduos brancos, educados e ricos.

Time-dependent decay of detectable antibodies against SARS-CoV-2: A comparison of ELISA with two batches of a lateral-flow test.

BACKGROUND: Large-scale epidemiological studies of seroprevalence of antibodies against SARS-CoV-2 often rely on point-of-care tests that provide immediate results to participants. Yet, little is known on how long rapid tests remain positive after the COVID-19 episode, or how much variability exists across different brands and even among batches of the same test. METHODS: In November 2020, we assessed the sensitivity of three tests applied to 133 individuals with a previous positive PCR result between April and October. All subjects provided finger prick blood samples for two batches (A and B) of the Wondfo lateral-flow IgG/IgM test, and dried blood spot samples for the S-UFRJ ELISA test. RESULTS: Overall sensitivity levels were 92.5% (95% CI 86.6-96.3), 63.2% (95% CI 54.4-71.4) and 33.8% (95% CI 25.9-42.5) for the S-UFRJ test, Wondfo A and Wondfo B tests, respectively. There was no evidence of a decline in the positivity of S-UFRJ with time since the diagnosis, but the two Wondfo batches showed sharp reductions to as low as 41.9% and 19.4%, respectively, for subjects with a positive PCR in June or earlier. Positive results for batch B of the rapid test were 35% to 54% lower than for batch A at any given month of diagnosis. INTERPRETATION: Whereas the ELISA test showed high sensitivity and stability of results over the five months of the study, both batches of the rapid test showed substantial declines, with one of the batches consistently showing lower sensitivity levels than the other. ELISA tests based on dried-blood spots are an inexpensive alternative to rapid lateral-flow tests in large-scale epidemiological studies. FUNDING: The study was funded by the "Todos Pela Saúde" initiative, Instituto Serrapilheira, Brazilian Ministry of Health, Brazilian Collective Health Association (ABRASCO) and the JBS S.A. initiative 'Fazer o Bem Faz Bem'.

Slow Spread of SARS-CoV-2 in Southern Brazil Over a 6-Month Period: Report on 8 Sequential Statewide Serological Surveys Including 35 611 Participants.

Objectives. To evaluate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over 6 months in the Brazilian State of Rio Grande do Sul (population 11.3 million), based on 8 serological surveys. Methods. In each survey, 4151 participants in round 1 and 4460 participants in round 2 were randomly sampled from all state regions. We assessed presence of antibodies against SARS-CoV-2 using a validated lateral flow point-of-care test; we adjusted figures for the time-dependent decay of antibodies. Results. The SARS-CoV-2 antibody prevalence increased from 0.03% (95% confidence interval [CI] = 0.00%, 0.34%; 1 in every 3333 individuals) in mid-April to 1.89% (95% CI = 1.36%, 2.54%; 1 in every 53 individuals) in early September. Prevalence was similar across gender and skin color categories. Older adults were less likely to be infected than younger participants. The proportion of the population who reported leaving home daily increased from 21.4% (95% CI = 20.2%, 22.7%) to 33.2% (95% CI = 31.8%, 34.5%). Conclusions. SARS-CoV-2 infection increased slowly during the first 6 months in the state, differently from what was observed in other Brazilian regions. Future survey rounds will continue to document the spread of the pandemic.

COVID-19 and social distancing among children and adolescents in Brazil.

OBJECTIVE: To estimate the prevalence of SARS-CoV-2 antibodies and the adherence to measures of social distancing in children and adolescents studied in three national surveys conducted in Brazil between May-June 2020. METHODS: Three national serological surveys were conducted in 133 sentinel cities located in all 27 Federative Units. Multistage probability sampling was used to select 250 individuals per city. The total sample size in age ranges 0-9 and 10-19 years old are of 4,263 and 8,024 individuals, respectively. Information on children or adolescents was gathered with a data collection app, and a rapid point-of-case test for SARS-CoV-2 was conducted on a finger prick blood sample. RESULTS: The adjusted prevalence of antibodies was 2.9% (2.2-3.6) among children 0-9 years, 2.2% (1.8-2.6) among adolescents 10-19 years, and 3.0% (2.7-3.3) among adults 20+years. Prevalence of antibodies was higher among poor children and adolescents compared to those of rich families. Adherence to social distancing measures was seen in 72.4% (71.9-73.8) of families with children, 60.8% (59.6-61.9) for adolescents, and 57.4% (56.9-57.8) for adults. For not leaving the house except for essential matters the proportions were 81.7% (80.5-82.9), 70.6% (69.6-61.9), and 65.1% (64.7-65.5), respectively. Among children and adolescents, social distancing was strongly associated with socioeconomic status, being much higher in the better-off families. CONCLUSIONS: The prevalence of antibodies against SARS-CoV-2 showed comparable levels among children, adolescents, and adults. Adherence to social distancing measures was more prevalent in children, followed by adolescents. There were important socioeconomic differences in the adherence to social distancing among children and adolescents.

High prevalence of symptoms among Brazilian subjects with antibodies against SARS-CoV-2.

Since the beginning of the pandemic of COVID-19, there has been a widespread assumption that most infected persons are asymptomatic. Using data from the recent wave of the EPICOVID19 study, a nationwide household-based survey including 133 cities from all states of Brazil, we estimated the proportion of people with and without antibodies for SARS-CoV-2 who were asymptomatic, which symptoms were most frequently reported, number of symptoms and the association with socio-demographic characteristics. We tested 33,205 subjects using a rapid antibody test previously validated. Information was collected before participants received the test result. Out of 849 (2.7%) participants positive for SARS-CoV-2 antibodies, only 12.1% (95% CI 10.1-14.5) reported no symptoms, compared to 42.2% (95% CI 41.7-42.8) among those negative. The largest difference between the two groups was observed for changes in smell/taste (56.5% versus 9.1%, a 6.2-fold difference). Changes in smell/taste, fever and body aches were most likely to predict positive tests as suggested by recursive partitioning tree analysis. Among individuals without any of these three symptoms, only 0.8% tested positive, compared to 18.3% of those with both fever and changes in smell or taste. Most subjects with antibodies against SARS-CoV-2 are symptomatic, even though most present only mild symptoms.

Patterns of Growth in Childhood in Relation to Adult Schooling Attainment and Intelligence Quotient in 6 Birth Cohorts in Low- and Middle-Income Countries: Evidence from the Consortium of Health-Oriented Research in Transitioning Societies (COHORTS).

BACKGROUND: Growth faltering has been associated with poor intellectual performance. The relative strengths of associations between growth in early and in later childhood remain underexplored. OBJECTIVES: We examined the association between growth in childhood and adult human capital in 5 low- and middle-income countries (LMICs). METHODS: We analyzed data from 9503 participants in 6 prospective birth cohorts from 5 LMICs (Brazil, Guatemala, India, the Philippines, and South Africa). We used linear and quasi-Poisson regression models to assess the associations between measures of height and relative weight at 4 age intervals [birth, age ∼2 y, midchildhood (MC), adulthood] and 2 dimensions of adult human capital [schooling attainment and Intelligence Quotient (IQ)]. RESULTS: Meta-analysis of site- and sex-specific estimates showed statistically significant associations between size at birth and height at ∼2 y and the 2 outcomes (P < 0.001). Weight and length at birth and linear growth from birth to ∼2 y of age (1 z-score difference) were positively associated with schooling attainment (ß: 0.13; 95% CI: 0.08, 0.19, ß: 0.17; 95% CI: 0.07, 0.32, and ß: 0.25, 95% CI: 0.10, 0.40, respectively) and adult IQ (ß: 0.74, 95% CI: 0.35, 1.14, ß: 0.73, 95% CI: 0.35, 1.10, and ß: 1.52, 95% CI: 0.96, 2.08, respectively). Linear growth from age 2 y to MC and from MC to adulthood was not associated with higher school attainment or IQ. Change in relative weight in early childhood, MC, and adulthood was not associated with either outcome. CONCLUSIONS: Linear growth in the first 1000 d is a predictor of schooling attainment and IQ in adulthood in LMICs. Linear growth in later periods was not associated with either of these outcomes. Changes in relative weight across the life course were not associated with schooling and IQ in adulthood.