International Journal of Environmental Research and Public Health
Validated physical activity (PA) questionnaires are crucial for collecting information in large e... more Validated physical activity (PA) questionnaires are crucial for collecting information in large epidemiological studies during childhood. Thus, this study analyzed the validity of a parent-reported PA questionnaire based on the Children’s Leisure Activities Study Survey by accelerometry in European children aged from 6 to 12 years old. We used data from 230 children of the Human Early-Life Exposome and Infancia y Medio Ambiente projects. Mean differences between moderate-to-vigorous PA (MVPA) reported by the questionnaire and the accelerometer were calculated (min/day), and its associated factors were explored by multiple robust linear regression. The agreement between methods was examined using a Bland–Altman plot. The concurrent validity of assessing MVPA was analyzed by cohort-adjusted Spearman’s partial correlations. ROC curve analysis was also used to explore the questionnaire’s capability to identify active children based on the World Health Organization guidelines. A moderate...
Introduction: In recent years, studies have emphasized the importance of air pollutants in the fo... more Introduction: In recent years, studies have emphasized the importance of air pollutants in the formation of reactive oxygen species and inflammation, leading to shorter telomere length and lower mt...
Background/Aim: Diet is the main source of exposure to several environmental contaminants, but th... more Background/Aim: Diet is the main source of exposure to several environmental contaminants, but the relative magnitude of various food groups is unknown. Our aim was to identify dietary determinants...
Ambient air pollution may play a role in childhood obesity development, but evidence is scarce, a... more Ambient air pollution may play a role in childhood obesity development, but evidence is scarce, and the modifying role of socioeconomic status (SES) is unclear. We aimed to examine the association between exposure to air pollution during early childhood and subsequent risk of developing overweight and obesity, and to evaluate whether SES is a modifier of this association. This longitudinal study included 416,955 children identified as normal weight between 2–5 years old and registered in an electronic primary healthcare record between 2006 and 2016 in Catalonia (Spain). Children were followed-up until they developed overweight or obesity, reached 15 years of age, died, transferred out, or end of study period (31/12/2018). Overweight and obesity were defined following the WHO reference obtained from height and weight measures. We estimated annual residential census levels of nitrogen dioxide (NO2) and particulate matter <10 μm (PM10), <2.5 μm (PM2.5), and 2.5–10 μm (PMcoarse) at study entry. We estimated the risk of developing overweight and obesity per interquartile range increase in air pollution exposure with Cox proportional hazard models. A total of 142,590 (34.2%) children developed overweight or obesity. Increased exposure to NO2, PM10, and PMcoarse was associated with a 2–3% increased risk of developing overweight and obesity (hazard ratio [HR] per 21.8 μg/m3 NO2 = 1.03 [95% CI: 1.02–1.04]; HR per 6.4 μg/m3 PM10 = 1.02 [95% CI: 1.02–1.03]; HR per 4.6 µg/m3 PMcoarse = 1.02, [95% CI: 1.01–1.02]). For all air pollutants, associations were stronger among children living in most compared to least deprived areas. This study suggests that early life exposure to air pollution may be associated with a small increase in the risk of developing overweight and obesity in childhood, and that this association may be exacerbated in the most deprived areas. Even these small associations are of potential global health importance because air pollution exposure is widespread and the long-term health consequences of childhood obesity are clear.
Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoro... more Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoroalkyl substances (PFAS), a group of endocrine disrupting chemicals. We hypothesized that early life exposure to PFASs is associated with poor metabolic health in children. We studied the association between prenatal and postnatal PFASs mixture exposure and cardiometabolic health in children, and the role of inflammatory proteins. In 1,101 mothers-child pairs from the Human Early Life Exposome project, we measured the concentrations of PFAS in blood collected in pregnancy and at 8 years (range = 6-12 years). We applied Bayesian Kernel Machine regression (BKMR) to estimate the associations between exposure to PFAS mixture and the cardiometabolic factors as age and sex- specific z-scores of waist circumference (WC), systolic and diastolic blood pressures (BP), and concentrations of triglycerides (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. We measured thirty six inflammatory biomarkers in child plasma and examined the underlying role of inflammatory status for the exposure-outcome association by integrating the three panels into a network. Exposure to the PFAS mixture was positively associated with HDL-C and systolic BP, and negatively associated with WC, LDL-C and TG. When we examined the independent effects of the individual chemicals in the mixture, prenatal PFHxS was negatively associated with HDL-C and prenatal PFNA was positively associated with WC and these were opposing directions from the overall mixture. Further, the network consisted of five distinct communities connected with positive and negative correlations. The selected inflammatory biomarkers were positively, while the postnatal PFAS were negatively related with the included cardiometabolic factors, and only prenatal PFOA was positively related with the pro-inflammatory cytokine IL-1beta and WC. Our study supports that prenatal, rather than postnatal, PFAS exposure might contribute to an unfavorable lipidemic profile and adiposity in childhood.
Exposure to chemical substances that can produce endocrine disrupting effects represents one of t... more Exposure to chemical substances that can produce endocrine disrupting effects represents one of the most critical public health threats nowadays. In line with the regulatory framework implemented within the European Union (EU) to reduce the levels of endocrine disruptors (EDs) for consumers, new and effective methods for ED testing are needed. The OBERON project will build an integrated testing strategy (ITS) to detect ED-related metabolic disorders by developing, improving and validating a battery of test systems. It will be based on the concept of an integrated approach for testing and assessment (IATA). OBERON will combine (1) experimental methods (in vitro, e.g., using 2D and 3D human-derived cells and tissues, and in vivo, i.e., using zebrafish at different stages), (2) high throughput omics technologies, (3) epidemiology and human biomonitoring studies and (4) advanced computational models (in silico and systems biology) on functional endpoints related to metabolism. Such inte...
International Journal of Environmental Research and Public Health, 2020
The assessment of early life socioeconomic position (SEP) is essential to the tackling of social ... more The assessment of early life socioeconomic position (SEP) is essential to the tackling of social inequalities in health. Although different indicators capture different SEP dimensions, maternal education is often used as the only indicator in birth cohort research, especially in multi-cohort analyses. Household income, as a direct measure of material resources, is one of the most important indicators, but one that is underused because it is difficult to measure through questionnaires. We propose a method to construct a standardized, cross-cohort comparable income indicator, the “Equivalized Household Income Indicator (EHII)”, which measures the equivalized disposable household income, using external data from the pan-European Union Statistics on Income and Living Conditions (EUSILC) surveys, and data from the cohorts. We apply this method to four studies, Piccolipiù and NINFEA from Italy and ELFE and EDEN from France, comparing the distribution of EHII with other SEP-related variabl...
Results from studies evaluating potential effects of prenatal exposure to radio-frequency electro... more Results from studies evaluating potential effects of prenatal exposure to radio-frequency electromagnetic fields from cell phones on birth outcomes have been inconsistent. Using data on 55,507 pregnant women and their children from Denmark (1996–2002), the Netherlands (2003–2004), Spain (2003–2008), and South Korea (2006–2011), we explored whether maternal cell-phone use was associated with pregnancy duration and fetal growth. On the basis of self-reported number of cell-phone calls per day, exposure was grouped as none, low (referent), intermediate, or high. We examined pregnancy duration (gestational age at birth, preterm/postterm birth), fetal growth (birth weight ratio, small/large size for gestational age), and birth weight variables (birth weight, low/high birth weight) and meta-analyzed cohort-specific estimates. The intermediate exposure group had a higher risk of giving birth at a lower gestational age (hazard ratio = 1.04, 95% confidence interval: 1.01, 1.07), and exposure...
International journal of obesity (2005), Jan 19, 2018
Maternal obesity and excessive gestational weight gain are associated with an increased risk of o... more Maternal obesity and excessive gestational weight gain are associated with an increased risk of obesity in offspring. It remains unclear whether maternal adiposity also affects organ fat, which has important adverse cardiometabolic health consequences and whether the associations reflect intrauterine causal mechanisms. We examined the associations of parental pre-pregnancy body mass index (BMI) and gestational weight gain with general, abdominal, pericardial, and liver fat in 10-year-old children. In a population-based prospective cohort study among 2354 parents and their children, we obtained pre-pregnancy maternal and paternal BMI and gestational weight gain and offspring BMI, fat mass index (total fat/height) by dual-energy X-ray absorptiometry, and subcutaneous fat index (subcutaneous fat/height), visceral fat index (visceral fat/height), pericardial fat index (pericardial fat/height), and liver fat fraction by magnetic resonance imaging (MRI) at 10 years. A 1-standard deviation...
Paediatric and perinatal epidemiology, Jan 4, 2016
Comparable evidence on adiposity inequalities in early life is lacking across a range of European... more Comparable evidence on adiposity inequalities in early life is lacking across a range of European countries. This study investigates whether low maternal education is associated with overweight and obesity risk in children from distinct European settings during early childhood. Prospective data of 45 413 children from 11 European cohorts were used. Children's height and weight obtained at ages 4-7 years were used to assess prevalent overweight and obesity according to the International Obesity Task Force definition. The Relative/Slope Indices of Inequality (RII/SII) were estimated within each cohort and by gender to investigate adiposity risk among children born to mothers with low education as compared to counterparts born to mothers with high education. Individual-data meta-analyses were conducted to obtain aggregate estimates and to assess heterogeneity between cohorts. Low maternal education yielded a substantial risk of early childhood adiposity across 11 European countries...
Journal of epidemiology and community health, Jan 24, 2015
A healthy start to life is a major priority in efforts to reduce health inequalities across Europ... more A healthy start to life is a major priority in efforts to reduce health inequalities across Europe, with important implications for the health of future generations. There is limited combined evidence on inequalities in health among newborns across a range of European countries. Prospective cohort data of 75 296 newborns from 12 European countries were used. Maternal education, preterm and small for gestational age births were determined at baseline along with covariate data. Regression models were estimated within each cohort and meta-analyses were conducted to compare and measure heterogeneity between cohorts. Mother's education was linked to an appreciable risk of preterm and small for gestational age (SGA) births across 12 European countries. The excess risk of preterm births associated with low maternal education was 1.48 (1.29 to 1.69) and 1.84 (0.99 to 2.69) in relative and absolute terms (Relative/Slope Index of Inequality, RII/SII) for all cohorts combined. Similar effe...
The exposome concept takes a holistic approach facilitated by new and emerging technologies to de... more The exposome concept takes a holistic approach facilitated by new and emerging technologies to describe 'the totality of human environmental (i.e. non-genetic) exposures from conception onwards, complementing the genome'. It provides a framework to advance the environmental epidemiology field that has until now focused almost exclusively on single-exposure health effects. The exposome includes an external domain, measured by methods including geo-spatial modelling, questionnaire and biomonitoring of external exposures while the internal domain is commonly assessed through molecular omics platforms. The internal domain, in part, reflects the biological response to the external domain. New statistical frameworks are required to integrate and assess exposome-health effects. The pregnancy period is a key starting point to describe the dynamic exposome, due to its heightened sensitivity and potential lifetime impact. A handful of studies have started to move towards an exposome...
SummaryEnvironmental exposures during early life play a critical role in life-course health, yet ... more SummaryEnvironmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1,301 mother-child pairs, we associated individual exposomes consisting of >100 chemical, physical and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, metabolome and proteins) in childhood. We identified 1,170 associations, 249 in pregnancy and 921 in childhood, which revealed potential biological responses and sources of exposure. The methylome best captures the persistent influence of pregnancy exposures, including maternal smoking; while childhood exposures were associated with features from all omics layers, revealing novel signatures for indoor air quality, essential trace elements, endocrine disruptors and weather conditions. This study provides a unique ...
Sparse data exist on the complex natural immunity to SARS-CoV-2 at the population level. We appli... more Sparse data exist on the complex natural immunity to SARS-CoV-2 at the population level. We applied a well-validated multiplex serology test in 5000 participants of a general population study in Catalonia in blood samples collected from end June to mid November 2020. Based on responses to fifteen isotype-antigen combinations, we detected a seroprevalence of 18.1% in adults (n = 4740), and modeled extrapolation to the general population of Catalonia indicated a 15.3% seroprevalence. Antibodies persisted up to 9 months after infection. Immune profiling of infected individuals revealed that with increasing severity of infection (asymptomatic, 1–3 symptoms, ≥ 4 symptoms, admitted to hospital/ICU), seroresponses were more robust and rich with a shift towards IgG over IgA and anti-spike over anti-nucleocapsid responses. Among seropositive participants, lower antibody levels were observed for those ≥ 60 years vs
International Journal of Environmental Research and Public Health
Validated physical activity (PA) questionnaires are crucial for collecting information in large e... more Validated physical activity (PA) questionnaires are crucial for collecting information in large epidemiological studies during childhood. Thus, this study analyzed the validity of a parent-reported PA questionnaire based on the Children’s Leisure Activities Study Survey by accelerometry in European children aged from 6 to 12 years old. We used data from 230 children of the Human Early-Life Exposome and Infancia y Medio Ambiente projects. Mean differences between moderate-to-vigorous PA (MVPA) reported by the questionnaire and the accelerometer were calculated (min/day), and its associated factors were explored by multiple robust linear regression. The agreement between methods was examined using a Bland–Altman plot. The concurrent validity of assessing MVPA was analyzed by cohort-adjusted Spearman’s partial correlations. ROC curve analysis was also used to explore the questionnaire’s capability to identify active children based on the World Health Organization guidelines. A moderate...
Introduction: In recent years, studies have emphasized the importance of air pollutants in the fo... more Introduction: In recent years, studies have emphasized the importance of air pollutants in the formation of reactive oxygen species and inflammation, leading to shorter telomere length and lower mt...
Background/Aim: Diet is the main source of exposure to several environmental contaminants, but th... more Background/Aim: Diet is the main source of exposure to several environmental contaminants, but the relative magnitude of various food groups is unknown. Our aim was to identify dietary determinants...
Ambient air pollution may play a role in childhood obesity development, but evidence is scarce, a... more Ambient air pollution may play a role in childhood obesity development, but evidence is scarce, and the modifying role of socioeconomic status (SES) is unclear. We aimed to examine the association between exposure to air pollution during early childhood and subsequent risk of developing overweight and obesity, and to evaluate whether SES is a modifier of this association. This longitudinal study included 416,955 children identified as normal weight between 2–5 years old and registered in an electronic primary healthcare record between 2006 and 2016 in Catalonia (Spain). Children were followed-up until they developed overweight or obesity, reached 15 years of age, died, transferred out, or end of study period (31/12/2018). Overweight and obesity were defined following the WHO reference obtained from height and weight measures. We estimated annual residential census levels of nitrogen dioxide (NO2) and particulate matter <10 μm (PM10), <2.5 μm (PM2.5), and 2.5–10 μm (PMcoarse) at study entry. We estimated the risk of developing overweight and obesity per interquartile range increase in air pollution exposure with Cox proportional hazard models. A total of 142,590 (34.2%) children developed overweight or obesity. Increased exposure to NO2, PM10, and PMcoarse was associated with a 2–3% increased risk of developing overweight and obesity (hazard ratio [HR] per 21.8 μg/m3 NO2 = 1.03 [95% CI: 1.02–1.04]; HR per 6.4 μg/m3 PM10 = 1.02 [95% CI: 1.02–1.03]; HR per 4.6 µg/m3 PMcoarse = 1.02, [95% CI: 1.01–1.02]). For all air pollutants, associations were stronger among children living in most compared to least deprived areas. This study suggests that early life exposure to air pollution may be associated with a small increase in the risk of developing overweight and obesity in childhood, and that this association may be exacerbated in the most deprived areas. Even these small associations are of potential global health importance because air pollution exposure is widespread and the long-term health consequences of childhood obesity are clear.
Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoro... more Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoroalkyl substances (PFAS), a group of endocrine disrupting chemicals. We hypothesized that early life exposure to PFASs is associated with poor metabolic health in children. We studied the association between prenatal and postnatal PFASs mixture exposure and cardiometabolic health in children, and the role of inflammatory proteins. In 1,101 mothers-child pairs from the Human Early Life Exposome project, we measured the concentrations of PFAS in blood collected in pregnancy and at 8 years (range = 6-12 years). We applied Bayesian Kernel Machine regression (BKMR) to estimate the associations between exposure to PFAS mixture and the cardiometabolic factors as age and sex- specific z-scores of waist circumference (WC), systolic and diastolic blood pressures (BP), and concentrations of triglycerides (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. We measured thirty six inflammatory biomarkers in child plasma and examined the underlying role of inflammatory status for the exposure-outcome association by integrating the three panels into a network. Exposure to the PFAS mixture was positively associated with HDL-C and systolic BP, and negatively associated with WC, LDL-C and TG. When we examined the independent effects of the individual chemicals in the mixture, prenatal PFHxS was negatively associated with HDL-C and prenatal PFNA was positively associated with WC and these were opposing directions from the overall mixture. Further, the network consisted of five distinct communities connected with positive and negative correlations. The selected inflammatory biomarkers were positively, while the postnatal PFAS were negatively related with the included cardiometabolic factors, and only prenatal PFOA was positively related with the pro-inflammatory cytokine IL-1beta and WC. Our study supports that prenatal, rather than postnatal, PFAS exposure might contribute to an unfavorable lipidemic profile and adiposity in childhood.
Exposure to chemical substances that can produce endocrine disrupting effects represents one of t... more Exposure to chemical substances that can produce endocrine disrupting effects represents one of the most critical public health threats nowadays. In line with the regulatory framework implemented within the European Union (EU) to reduce the levels of endocrine disruptors (EDs) for consumers, new and effective methods for ED testing are needed. The OBERON project will build an integrated testing strategy (ITS) to detect ED-related metabolic disorders by developing, improving and validating a battery of test systems. It will be based on the concept of an integrated approach for testing and assessment (IATA). OBERON will combine (1) experimental methods (in vitro, e.g., using 2D and 3D human-derived cells and tissues, and in vivo, i.e., using zebrafish at different stages), (2) high throughput omics technologies, (3) epidemiology and human biomonitoring studies and (4) advanced computational models (in silico and systems biology) on functional endpoints related to metabolism. Such inte...
International Journal of Environmental Research and Public Health, 2020
The assessment of early life socioeconomic position (SEP) is essential to the tackling of social ... more The assessment of early life socioeconomic position (SEP) is essential to the tackling of social inequalities in health. Although different indicators capture different SEP dimensions, maternal education is often used as the only indicator in birth cohort research, especially in multi-cohort analyses. Household income, as a direct measure of material resources, is one of the most important indicators, but one that is underused because it is difficult to measure through questionnaires. We propose a method to construct a standardized, cross-cohort comparable income indicator, the “Equivalized Household Income Indicator (EHII)”, which measures the equivalized disposable household income, using external data from the pan-European Union Statistics on Income and Living Conditions (EUSILC) surveys, and data from the cohorts. We apply this method to four studies, Piccolipiù and NINFEA from Italy and ELFE and EDEN from France, comparing the distribution of EHII with other SEP-related variabl...
Results from studies evaluating potential effects of prenatal exposure to radio-frequency electro... more Results from studies evaluating potential effects of prenatal exposure to radio-frequency electromagnetic fields from cell phones on birth outcomes have been inconsistent. Using data on 55,507 pregnant women and their children from Denmark (1996–2002), the Netherlands (2003–2004), Spain (2003–2008), and South Korea (2006–2011), we explored whether maternal cell-phone use was associated with pregnancy duration and fetal growth. On the basis of self-reported number of cell-phone calls per day, exposure was grouped as none, low (referent), intermediate, or high. We examined pregnancy duration (gestational age at birth, preterm/postterm birth), fetal growth (birth weight ratio, small/large size for gestational age), and birth weight variables (birth weight, low/high birth weight) and meta-analyzed cohort-specific estimates. The intermediate exposure group had a higher risk of giving birth at a lower gestational age (hazard ratio = 1.04, 95% confidence interval: 1.01, 1.07), and exposure...
International journal of obesity (2005), Jan 19, 2018
Maternal obesity and excessive gestational weight gain are associated with an increased risk of o... more Maternal obesity and excessive gestational weight gain are associated with an increased risk of obesity in offspring. It remains unclear whether maternal adiposity also affects organ fat, which has important adverse cardiometabolic health consequences and whether the associations reflect intrauterine causal mechanisms. We examined the associations of parental pre-pregnancy body mass index (BMI) and gestational weight gain with general, abdominal, pericardial, and liver fat in 10-year-old children. In a population-based prospective cohort study among 2354 parents and their children, we obtained pre-pregnancy maternal and paternal BMI and gestational weight gain and offspring BMI, fat mass index (total fat/height) by dual-energy X-ray absorptiometry, and subcutaneous fat index (subcutaneous fat/height), visceral fat index (visceral fat/height), pericardial fat index (pericardial fat/height), and liver fat fraction by magnetic resonance imaging (MRI) at 10 years. A 1-standard deviation...
Paediatric and perinatal epidemiology, Jan 4, 2016
Comparable evidence on adiposity inequalities in early life is lacking across a range of European... more Comparable evidence on adiposity inequalities in early life is lacking across a range of European countries. This study investigates whether low maternal education is associated with overweight and obesity risk in children from distinct European settings during early childhood. Prospective data of 45 413 children from 11 European cohorts were used. Children's height and weight obtained at ages 4-7 years were used to assess prevalent overweight and obesity according to the International Obesity Task Force definition. The Relative/Slope Indices of Inequality (RII/SII) were estimated within each cohort and by gender to investigate adiposity risk among children born to mothers with low education as compared to counterparts born to mothers with high education. Individual-data meta-analyses were conducted to obtain aggregate estimates and to assess heterogeneity between cohorts. Low maternal education yielded a substantial risk of early childhood adiposity across 11 European countries...
Journal of epidemiology and community health, Jan 24, 2015
A healthy start to life is a major priority in efforts to reduce health inequalities across Europ... more A healthy start to life is a major priority in efforts to reduce health inequalities across Europe, with important implications for the health of future generations. There is limited combined evidence on inequalities in health among newborns across a range of European countries. Prospective cohort data of 75 296 newborns from 12 European countries were used. Maternal education, preterm and small for gestational age births were determined at baseline along with covariate data. Regression models were estimated within each cohort and meta-analyses were conducted to compare and measure heterogeneity between cohorts. Mother's education was linked to an appreciable risk of preterm and small for gestational age (SGA) births across 12 European countries. The excess risk of preterm births associated with low maternal education was 1.48 (1.29 to 1.69) and 1.84 (0.99 to 2.69) in relative and absolute terms (Relative/Slope Index of Inequality, RII/SII) for all cohorts combined. Similar effe...
The exposome concept takes a holistic approach facilitated by new and emerging technologies to de... more The exposome concept takes a holistic approach facilitated by new and emerging technologies to describe 'the totality of human environmental (i.e. non-genetic) exposures from conception onwards, complementing the genome'. It provides a framework to advance the environmental epidemiology field that has until now focused almost exclusively on single-exposure health effects. The exposome includes an external domain, measured by methods including geo-spatial modelling, questionnaire and biomonitoring of external exposures while the internal domain is commonly assessed through molecular omics platforms. The internal domain, in part, reflects the biological response to the external domain. New statistical frameworks are required to integrate and assess exposome-health effects. The pregnancy period is a key starting point to describe the dynamic exposome, due to its heightened sensitivity and potential lifetime impact. A handful of studies have started to move towards an exposome...
SummaryEnvironmental exposures during early life play a critical role in life-course health, yet ... more SummaryEnvironmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1,301 mother-child pairs, we associated individual exposomes consisting of >100 chemical, physical and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, metabolome and proteins) in childhood. We identified 1,170 associations, 249 in pregnancy and 921 in childhood, which revealed potential biological responses and sources of exposure. The methylome best captures the persistent influence of pregnancy exposures, including maternal smoking; while childhood exposures were associated with features from all omics layers, revealing novel signatures for indoor air quality, essential trace elements, endocrine disruptors and weather conditions. This study provides a unique ...
Sparse data exist on the complex natural immunity to SARS-CoV-2 at the population level. We appli... more Sparse data exist on the complex natural immunity to SARS-CoV-2 at the population level. We applied a well-validated multiplex serology test in 5000 participants of a general population study in Catalonia in blood samples collected from end June to mid November 2020. Based on responses to fifteen isotype-antigen combinations, we detected a seroprevalence of 18.1% in adults (n = 4740), and modeled extrapolation to the general population of Catalonia indicated a 15.3% seroprevalence. Antibodies persisted up to 9 months after infection. Immune profiling of infected individuals revealed that with increasing severity of infection (asymptomatic, 1–3 symptoms, ≥ 4 symptoms, admitted to hospital/ICU), seroresponses were more robust and rich with a shift towards IgG over IgA and anti-spike over anti-nucleocapsid responses. Among seropositive participants, lower antibody levels were observed for those ≥ 60 years vs
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