Lifecourse trajectories and cross-generational trends in social isolation: Findings from five successive British birth cohort studies.

Despite growing concerns in the UK about social isolation, there remains a lack of data on the extent and time trends of social isolation from longitudinal, population-based studies. There is also little research that assesses the multiple domains of social isolation across the lifecourse and between generations in a holistic way accounting for different contexts. By applying a multi-context, multi-domain framework of social isolation to 5 successive British birth cohorts, we provide conceptual and empirical understanding of social isolation trajectories across the lifecourse and identify potential generational and sex differences in trends. Where data were available, comparable social isolation indicators were generated to enable lifecourse trajectories and cross-generational trends to be explored. Information on isolation was available across the following relational contexts: household i.e., living alone; partnership, family and friends outside the household; education and employment networks; and community engagement. Trajectories were modelled stratified by sex using a multilevel growth curve framework. Data were analysed from 73,847 individuals (48.5% female), in 5 successive cohorts born in 1946 (N = 5,362), 1958 (N = 16,742), 1970 (N = 16,950), 1989-90 (N = 15,562), and 2000-01 (N = 19,231). Exploring a range of social isolation indicators across several contexts provided a nuanced picture of social isolation across the lifecourse and between generations in the UK, with no consistent pattern of increased or decreased isolation over time. For example, more people are living alone, less women are out of education and employment in midlife, more people are volunteering, but fewer people regularly engage in religious activity. It therefore highlights the need to focus on a range of social isolation indicators across contexts to understand how people compensate for specific types of isolation, and to understand structural differences in social configurations in the UK, which may not only define the timing and sequencing of life transitions but also social isolation.

Long COVID and financial outcomes: evidence from four longitudinal population surveys.

BACKGROUND: Long-term sequelae of COVID-19 (long COVID) include muscle weakness, fatigue, breathing difficulties and sleep disturbance over weeks or months. Using UK longitudinal data, we assessed the relationship between long COVID and financial disruption. METHODS: We estimated associations between long COVID (derived using self-reported length of COVID-19 symptoms) and measures of financial disruption (subjective financial well-being, new benefit claims, changes in household income) by analysing data from four longitudinal population studies, gathered during the first year of the pandemic. We employed modified Poisson regression in a pooled analysis of the four cohorts adjusting for a range of potential confounders, including pre-pandemic (pre-long COVID) factors. RESULTS: Among the 20 112 observations across four population surveys, 13% reported having COVID-19 with symptoms that impeded their ability to function normally-10.7% had such symptoms for <4 weeks (acute COVID-19), 1.2% had such symptoms for 4-12 weeks (ongoing symptomatic COVID-19) and 0.6% had such symptoms for >12 weeks (post-COVID-19 syndrome). We found that post-COVID-19 syndrome was associated with worse subjective financial well-being (adjusted relative risk ratios (aRRRs)=1.57, 95% CI=1.25, 1.96) and new benefit claims (aRRR=1.79, CI=1.27, 2.53). Associations were broadly similar across sexes and education levels. These results were not meaningfully altered when scaled to represent the population by age. CONCLUSIONS: Long COVID was associated with financial disruption in the UK. If our findings reflect causal effects, extending employment protection and financial support to people with long COVID may be warranted.

Examining the quality and population representativeness of linked survey and administrative data: guidance and illustration using linked 1958 National Child Development Study and Hospital Episode Statistics data.

Introduction: Recent years have seen an increase in linkages between survey and administrative data. It is important to evaluate the quality of such data linkages to discern the likely reliability of ensuing research. Evaluation of linkage quality and bias can be conducted using different approaches, but many of these are not possible when there is a separation of processes for linkage and analysis to help preserve privacy, as is typically the case in the UK (and elsewhere). Objectives: We aimed to describe a suite of generalisable methods to evaluate linkage quality and population representativeness of linked survey and administrative data which remain tractable when users of the linked data are not party to the linkage process itself. We emphasise issues particular to longitudinal survey data throughout. Methods: Our proposed approaches cover several areas: i) Linkage rates, ii) Selection into response, linkage consent and successful linkage, iii) Linkage quality, and iv) Linked data population representativeness. We illustrate these methods using a recent linkage between the 1958 National Child Development Study (NCDS; a cohort following an initial 17,415 people born in Great Britain in a single week of 1958) and Hospital Episode Statistics (HES) databases (containing important information regarding admissions, accident and emergency attendances and outpatient appointments at NHS hospitals in England). Results: Our illustrative analyses suggest that the linkage quality of the NCDS-HES data is high and that the linked sample maintains an excellent level of population representativeness with respect to the single dimension we assessed. Conclusions: Through this work we hope to encourage providers and users of linked data resources to undertake and publish thorough evaluations. We further hope that providing illustrative analyses using linked NCDS-HES data will improve the quality and transparency of research using this particular linked data resource.

Life-course social participation and physical activity in midlife: longitudinal associations in the 1970 British Cohort Study (BCS70).

A hypothesized benefit of social participation is that it encourages people to be more physically active. However, limited evidence exists on the association between social participation over the life-course and physical activity in midlife. We sought to apply a life-course framework to examine the association of social participation and device measured physical activity in midlife in the UK. We used the 1970 British Birth Cohort Study (BCS70), which includes all people born in Britain during a single week in 1970. Social participation was assessed at ages 16, 30, 34 and 42. Physical activity was measured by accelerometery at age 46, as mean daily step count and time spent in moderate to vigorous physical activity (MVPA). The associations of social participation and physical activity were tested using two different life-course models: the sensitive period model and the accumulation model. Individuals with medium and high participation compared to no social participation over their life-course had higher mean daily step count and MVPA in midlife, supporting the accumulation model. In the sensitive period model, only those that actively participated at age 42 had higher mean daily steps and MVPA compared to those who did not participate. Our study provides empirical evidence on the importance of sustaining social participation at all ages over the life-course rather than at a particular timepoint of someone's life. If our findings reflect causal effects, interventions to promote social participation throughout the life-course could be an avenue to promote physical activity in middle life.

Generational differences in physical health and disability in the United States and Europe.

Objectives: Declines in mortality have typically been associated with improvements in physical health across generations. While life expectancy in most high-income countries continues to increase, there is evidence that younger generations, particularly in the United States (US), are less healthy than previous generations at the same age. We compared generational trends in physical health in the US, England, and continental Europe to explore whether other regions have experienced a similar pattern of worsening health across cohorts. Methods: Using data from nationally representative studies of adults aged ≥50 years from the US (Health and Retirement Study, n=26,939), England (English Longitudinal Study of Ageing, n=14,992) and 11 continental European countries (Survey of Health, Ageing and Retirement in Europe, n=72,595), we estimated differences in the age-adjusted prevalence of self-reported chronic disease and disability and observer-measured health indicators across pseudo-birth cohorts (born <1925, 1925-1935, 1936-1945, 1946-1954, 1955-1959). Results: Age-adjusted prevalence of doctor-diagnosed chronic disease increased across cohorts in all regions. Trends in disability prevalence were more regionally varied. Still, in both the US and Europe, we observed a structural break in disability trends, with declines observed in pre-war cohorts slowing, stalling, or reversing for cohorts born since 1945. Discussion: In all regions, we found evidence for worsening health across cohorts, particularly for those born since 1945. While more chronic disease in younger cohorts need not necessarily translate to worse quality of life or higher rates of functional limitation, there is some suggestion that worsening chronic disease morbidity may be spilling over into worsening disability.

A quantitative approach to the intersectional study of mental health inequalities during the COVID-19 pandemic in UK young adults.

PURPOSE: Mental health inequalities across social identities/positions during the COVID-19 pandemic have been mostly reported independently from each other or in a limited way (e.g., at the intersection between age and sex or gender). We aim to provide an inclusive socio-demographic mapping of different mental health measures in the population using quantitative methods that are consistent with an intersectional perspective. METHODS: Data included 8,588 participants from two British cohorts (born in 1990 and 2000-2002, respectively), collected in February/March 2021 (during the third UK nationwide lockdown). Measures of anxiety and depressive symptomatology, loneliness, and life satisfaction were analysed using Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) models. RESULTS: We found evidence of large mental health inequalities across intersectional strata. Large proportions of those inequalities were accounted for by the additive effects of the variables used to define the intersections, with some of the largest gaps associated with sexual orientation (with sexual minority groups showing substantially worse outcomes). Additional inequalities were found by cohort/generation, birth sex, racial/ethnic groups, and socioeconomic position. Intersectional effects were observed mostly in intersections defined by combinations of privileged and marginalised social identities/positions (e.g., lower-than-expected life satisfaction in South Asian men in their thirties from a sexual minority and a disadvantaged childhood social class). CONCLUSION: We found substantial inequalities largely cutting across intersectional strata defined by multiple co-constituting social identities/positions. The large gaps found by sexual orientation extend the existing evidence that sexual minority groups were disproportionately affected by the pandemic. Study implications and limitations are discussed.

Fast food proximity and weight gain in childhood and adolescence: Evidence from Great Britain.

We study the relationship between proximity to fast food restaurants and weight gain from late childhood to early adolescence. We use the Millennium Cohort Study, a UK-wide nationally representative longitudinal study, linked with granular geocoded food outlet data to measure the presence of fast food outlets around children's homes and schools from ages 7 to 14. We find that proximity to fast food outlets is associated with increased weight (body mass index, overweight, obese, body fat, weight), but only among those with maternal education below degree level. Within this sample, those with lower levels of emotional regulation are at heightened risk of weight gain.

Using linked administrative data to aid the handling of non-response and restore sample representativeness in cohort studies: the 1958 national child development study and hospital episode statistics data.

BACKGROUND: There is growing interest in whether linked administrative data have the potential to aid analyses subject to missing data in cohort studies. METHODS: Using linked 1958 National Child Development Study (NCDS; British cohort born in 1958, n = 18,558) and Hospital Episode Statistics (HES) data, we applied a LASSO variable selection approach to identify HES variables which are predictive of non-response at the age 55 sweep of NCDS. We then included these variables as auxiliary variables in multiple imputation (MI) analyses to explore the extent to which they helped restore sample representativeness of the respondents together with the imputed non-respondents in terms of early life variables (father's social class at birth, cognitive ability at age 7) and relative to external population benchmarks (educational qualifications and marital status at age 55). RESULTS: We identified 10 HES variables that were predictive of non-response at age 55 in NCDS. For example, cohort members who had been treated for adult mental illness had more than 70% greater odds of bring non-respondents (odds ratio 1.73; 95% confidence interval 1.17, 2.51). Inclusion of these HES variables in MI analyses only helped to restore sample representativeness to a limited extent. Furthermore, there was essentially no additional gain in sample representativeness relative to analyses using only previously identified survey predictors of non-response (i.e. NCDS rather than HES variables). CONCLUSIONS: Inclusion of HES variables only aided missing data handling in NCDS to a limited extent. However, these findings may not generalise to other analyses, cohorts or linked administrative datasets. This work provides a demonstration of the use of linked administrative data for the handling of missing cohort data which we hope will act as template for others.

Differences in the impact of the COVID-19 pandemic in the long-term trajectories of life satisfaction by sex in the UK: a prospective cohort study.

BACKGROUND: The COVID-19 pandemic has disproportionately affected women's mental health, with most evidence focused on mental ill-health outcomes. Previous research suggests that differences in time-use might explain this disparity, as women generally spent more time doing psychologically taxing activities than men. We investigated (1) sex differences in the impact of the pandemic in the long-term trajectories of life satisfaction and (2) whether time-use differences partly explained that differential impact. METHODS: In this prospective cohort study, we used the 1970 British Cohort Study, a birth cohort representing people born in Great Britain in 1970. Since 1970, information has been collected for all cohort members every 4-10 years (ten sweeps). Additional data were collected at three timepoints during the pandemic (May 2020, September-October 2020, February-March 2021) as part of the COVID-19 Survey. Response rates within the target population ranged between 23·6% (May, 2020) and 32·5% (March, 2021) in the COVID-19 Survey. We used non-response weights to restore sample representativeness to the target population (cohort members alive and residing in the UK during the pandemic). Life satisfaction was prospectively assessed at ages 26 (1996), 30, 34, 42, 46, 50, 50·5, and 51 years (2021) using a single question with responses ranging from 0 (lowest life satisfaction) to 10 (highest life satisfaction). We used multiple-group piecewise latent growth curve models grouped by sex assigned at birth. Additional models were adjusted for self-reported number of hours spent working, volunteering, home-schooling children, taking care of children and other people, and doing housework during the pandemic. Participants provided verbal informed consent. Ethics approval was not sought as non-sensitive, open-access data with minimal risk of identification was used. FINDINGS: We analysed data from 6766 adults (3799 [56·2%] women and 2967 [43·8%] men). Compared with men, women had consistently higher levels of life satisfaction before the pandemic (Δintercept,unadjusted = 0·213, 95% CI 0·087 to 0·340, p=0·0009), and experienced a more accelerated decline with its onset (Δquad2,unadjusted = -0·018, -0·026 to -0·011; p<0·0001), even after accounting for time use (Δquad2,adjusted = -0·016, -0·031 to -0·001; p=0·0348). Results were robust to adjustment for concurrent financial and occupational situation (Δquad2,adjustedfull = -0·019, -0·035 to -0·004; p=0·0158). INTERPRETATION: Our study shows sex inequalities in the impact of the pandemic on the long-term life satisfaction trajectories of adults in their 50s. Self-reported time-use differences did not account for these inequalities. One of the limitations is that we relied on self-reported time-use and were not able to include factors like the so-called mental load (being responsible for organising or monitoring activities, regardless of being involved in their execution), which might partly explain these results. FUNDING: Economic and Social Research Council (ESRC) Centre for Society and Mental Health at King's College London.

Associations between SARS-CoV-2 infection and subsequent economic inactivity and employment status: pooled analyses of five linked longitudinal surveys.

Introduction: Following the acute phase of the COVID-19 pandemic, record numbers of people became economically inactive (i.e., neither working nor looking for work), or non-employed (including unemployed job seekers and economically inactive people). A possible explanation is people leaving the workforce after contracting COVID-19. We investigated whether testing positive for SARS-CoV-2 is related to subsequent economic inactivity and non-employment, among people employed pre-pandemic. Methods: The data came from five UK longitudinal population studies held by both the UK Longitudinal Linkage Collaboration (UK LLC; primary analyses) and the UK Data Service (UKDS; secondary analyses). We pooled data from five long established studies (1970 British Cohort Study, English Longitudinal Study of Ageing, 1958 National Child Development Study, Next Steps, and Understanding Society). The study population were aged 25-65 years between March 2020 to March 2021 and employed pre-pandemic. Outcomes were economic inactivity and non-employment measured at the time of the last follow-up survey (November 2020 to March 2021, depending on study). For the UK LLC sample (n=8,174), COVID-19 infection was indicated by a positive SARS-CoV-2 test in NHS England records. For the UKDS sample we used self-reported measures of COVID-19 infection (n=13,881). Logistic regression models estimated odds ratios (ORs) with 95% confidence intervals (95%CIs) adjusting for potential confounders including sociodemographic variables, pre-pandemic health and occupational class. Results: Testing positive for SARS-CoV-2 was very weakly associated with economic inactivity (OR 1.08 95%CI 0.68-1.73) and non-employment status (OR 1.09. 95%CI 0.77-1.55) in the primary analyses. In secondary analyses, self-reported test-confirmed COVID-19 was not associated with either economic inactivity (OR 1.01 95%CI 0.70-1.44) or non-employment status (OR 1.03 95%CI 0.79-1.35). Conclusions: Among people employed pre-pandemic, testing positive for SARS-CoV-2 was either weakly or not associated with increased economic inactivity or non-employment. Research on the recent increases in economic inactivity should focus on other potential causes.

Genetic impacts on DNA methylation help elucidate regulatory genomic processes.

BACKGROUND: Pinpointing genetic impacts on DNA methylation can improve our understanding of pathways that underlie gene regulation and disease risk. RESULTS: We report heritability and methylation quantitative trait locus (meQTL) analysis at 724,499 CpGs profiled with the Illumina Infinium MethylationEPIC array in 2358 blood samples from three UK cohorts. Methylation levels at 34.2% of CpGs are affected by SNPs, and 98% of effects are cis-acting or within 1 Mbp of the tested CpG. Our results are consistent with meQTL analyses based on the former Illumina Infinium HumanMethylation450 array. Both SNPs and CpGs with meQTLs are overrepresented in enhancers, which have improved coverage on this platform compared to previous approaches. Co-localisation analyses across genetic effects on DNA methylation and 56 human traits identify 1520 co-localisations across 1325 unique CpGs and 34 phenotypes, including in disease-relevant genes, such as USP1 and DOCK7 (total cholesterol levels), and ICOSLG (inflammatory bowel disease). Enrichment analysis of meQTLs and integration with expression QTLs give insights into mechanisms underlying cis-meQTLs (e.g. through disruption of transcription factor binding sites for CTCF and SMC3) and trans-meQTLs (e.g. through regulating the expression of ACD and SENP7 which can modulate DNA methylation at distal sites). CONCLUSIONS: Our findings improve the characterisation of the mechanisms underlying DNA methylation variability and are informative for prioritisation of GWAS variants for functional follow-ups. The MeQTL EPIC Database and viewer are available online at https://epicmeqtl.kcl.ac.uk .

Social Health and Change in Cognitive Capability among Older Adults: Findings from Four European Longitudinal Studies.

INTRODUCTION: In this study, we examine whether social health markers measured at baseline are associated with differences in cognitive capability and the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies. METHODS: We applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline. RESULTS: Pooled estimates show distinct relationships between markers of social health and cognitive domains, e.g., a large network size (≥6 people vs. none) was associated with higher executive function (0.17 standard deviation [SD] [95% CI: 0.00, 0.34], I2 = 27%) but not with memory (0.08 SD [95% CI: -0.02, 0.18], I2 = 19%). We also observed pooled associations between being married or cohabiting, having a large network size, and participating in social activities with slower decline in cognitive capability. However, estimates were close to zero, e.g., 0.01 SD/year (95% CI: 0.01, 0.02) I2 = 19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous, and results for average memory were the most heterogeneous. CONCLUSION: Overall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between-study differences and considering the context specificity of findings in developing and deploying interventions.

The performance of long vs. short questionnaire-based measures of depression, anxiety, and psychological distress among UK adults: A comparison of the patient health questionnaires, generalized anxiety disorder scales, malaise inventory, and Kessler scales.

It is often important to minimise the time participants in social science studies spend on completing questionnaire-based measures, reducing response burden, and increasing data quality. Here, we investigated the performance of the short versions of some widely used depression, anxiety, and psychological distress scales and compared them to the performance of longer versions of these scales (PHQ-2 vs PHQ-9, GAD-2 vs GAD-7, Malaise-3 vs Malaise-9, K6 vs K10). Across a sample of UK adults (N = 987, ages 18-86), we tested the existing factor structure and accuracy of the scales through confirmatory factor analyses and exploration of the total information functions, observing adequate model fit indices across the measures. Measurement invariance was tested across birth sex and age groups to explore whether any differences in measurement properties or measurement bias may exist, finding support for the invariance of most measures. We conducted bivariate correlations across the measures as a way of obtaining evidence of the equivalence in the rank-ordering of short vs long scales. The results followed a similar pattern across the young adult subsample (N = 375, ages 18-39) as in the overall sample. Overall, these results indicate that the short forms of the tested scales may perform similarly to the full versions. Where brevity is important, researchers may opt to use the shorter versions of the scales based on these data.

Home working and social and mental wellbeing at different stages of the COVID-19 pandemic in the UK: Evidence from 7 longitudinal population surveys.

BACKGROUND: Home working has increased since the Coronavirus Disease 2019 (COVID-19) pandemic's onset with concerns that it may have adverse health implications. We assessed the association between home working and social and mental wellbeing among the employed population aged 16 to 66 through harmonised analyses of 7 UK longitudinal studies. METHODS AND FINDINGS: We estimated associations between home working and measures of psychological distress, low life satisfaction, poor self-rated health, low social contact, and loneliness across 3 different stages of the pandemic (T1 = April to June 2020 -first lockdown, T2 = July to October 2020 -eased restrictions, T3 = November 2020 to March 2021 -second lockdown) using modified Poisson regression and meta-analyses to pool results across studies. We successively adjusted the model for sociodemographic characteristics (e.g., age, sex), job characteristics (e.g., sector of activity, pre-pandemic home working propensities), and pre-pandemic health. Among respectively 10,367, 11,585, and 12,179 participants at T1, T2, and T3, we found higher rates of home working at T1 and T3 compared with T2, reflecting lockdown periods. Home working was not associated with psychological distress at T1 (RR = 0.92, 95% CI = 0.79 to 1.08) or T2 (RR = 0.99, 95% CI = 0.88 to 1.11), but a detrimental association was found with psychological distress at T3 (RR = 1.17, 95% CI = 1.05 to 1.30). Study limitations include the fact that pre-pandemic home working propensities were derived from external sources, no information was collected on home working dosage and possible reverse association between change in wellbeing and home working likelihood. CONCLUSIONS: No clear evidence of an association between home working and mental wellbeing was found, apart from greater risk of psychological distress during the second lockdown, but differences across subgroups (e.g., by sex or level of education) may exist. Longer term shifts to home working might not have adverse impacts on population wellbeing in the absence of pandemic restrictions but further monitoring of health inequalities is required.

Long-term psychological distress trajectories and the COVID-19 pandemic in three British birth cohorts: A multi-cohort study.

BACKGROUND: Growing evidence suggests that population mental health outcomes have worsened since the pandemic started. The extent that these changes have altered common age-related trends in psychological distress, where distress typically rises until midlife and then falls after midlife in both sexes, is unknown. We aimed to analyse whether long-term pre-pandemic psychological distress trajectories were disrupted during the pandemic, and whether these changes have been different across cohorts and by sex. METHODS AND FINDINGS: We used data from three nationally representative birth cohorts comprising all people born in Great Britain in a single week of 1946 (National Survey of Health and Development, NSHD), 1958 (National Child Development Study, NCDS), or 1970 (British Cohort Study, BCS70). The follow-up data used spanned 39 years in NSHD (1982 to 2021), 40 years in NCDS (1981 to 2001), and 25 years in BCS70 (1996 to 2021). We used psychological distress factor scores, as measured by validated self-reported questionnaires (NSHD: Present State Examination, Psychiatric Symptoms Frequency, and 28- and 12-item versions of General Health Questionnaire; NCDS and BCS70: Malaise Inventory; all: 2-item versions of Generalized Anxiety Disorder scale and Patient Health Questionnaire). We used a multilevel growth curve modelling approach to model the trajectories of distress across cohorts and sexes and obtained estimates of the differences between the distress levels observed during the pandemic and those observed at the most recent pre-pandemic assessment and at the peak in the cohort-specific pre-pandemic distress trajectory, located at midlife. We further analysed whether pre-existing cohort and sex inequalities had changed with the pandemic onset using a difference-in-differences (DiD) approach. The analytic sample included 16,389 participants. By September/October 2020, distress levels had reached or exceeded the levels of the peak in the pre-pandemic life-course trajectories, with larger increases in younger cohorts (standardised mean differences [SMD] and 95% confidence intervals of SMDNSHD,pre-peak = -0.02 [-0.07, 0.04], SMDNCDS,pre-peak = 0.05 [0.02, 0.07], and SMDBCS70,pre-peak = 0.09 [0.07, 0.12] for the 1946, 1958, and 1970 birth cohorts, respectively). Increases in distress were larger among women than men, widening pre-existing sex inequalities (DiD and 95% confidence intervals of DiDNSHD,sex,pre-peak = 0.17 [0.06, 0.28], DiDNCDS,sex,pre-peak = 0.11 [0.07, 0.16], and DiDBCS70,sex,pre-peak = 0.11 [0.05, 0.16] when comparing sex inequalities in the pre-pandemic peak in midlife to those observed by September/October 2020). As expected in cohort designs, our study suffered from high proportions of attrition with respect to the original samples. Although we used non-response weights to restore sample representativeness to the target populations (those born in the United Kingdom in 1946, 1958, and 1970, alive and residing in the UK), results may not be generalisable to other sections within the UK population (e.g., migrants and ethnic minority groups) and countries different than the UK. CONCLUSIONS: Pre-existing long-term psychological distress trajectories of adults born between 1946 and 1970 were disrupted during the COVID-19 pandemic, particularly among women, who reached the highest levels ever recorded in up to 40 years of follow-up data. This may impact future trends of morbidity, disability, and mortality due to common mental health problems.

Clustering of adverse health and educational outcomes in adolescence following early childhood disadvantage: population-based retrospective UK cohort study.

BACKGROUND: Disadvantage in early childhood (ages 0-5 years) is associated with worse health and educational outcomes in adolescence. Evidence on the clustering of these adverse outcomes by household income is scarce in the generation of adolescents born since the turn of the millennium. We aimed to describe the association between household income in early childhood and physical health, psychological distress, smoking behaviour, obesity, and educational outcomes at age 17 years, including the patterning and clustering of these five outcomes by income quintiles. METHODS: In this population-based, retrospective cohort study, we used data from the Millennium Cohort Study in which individuals born in the UK between Sept 1, 2000, and Jan 1, 2002, were followed up. We collected data on five adverse health and social outcomes in adolescents aged 17 years known to limit life chances: psychological distress, self-assessed ill health, smoking, obesity, and poor educational achievement. We compared how single and multiple outcomes were distributed across early childhood quintile groups of income, as an indicator of disadvantage, and modelled the potential effect of three income-shifting scenarios in early childhood for reducing adverse outcomes in adolescence. FINDINGS: We included 15 245 adolescents aged 17 years, 7788 (51·1%) of whom were male and 7457 (48·9%) of whom were female. Adolescents in the lowest income quintile group in childhood were 12·7 (95% CI 6·4-25·1) times more likely than those in the highest quintile group to have four or five adverse adolescent outcomes, with poor educational achievement (risk ratio [RR] 4·6, 95% CI 4·2-5·0) and smoking (3·6, 3·0-4·2), showing the largest single risk ratios. Shifting up to the second lowest, middle, and highest income groups would reduce multiple adolescent adversities by 4·9% (95% CI -23·8 to 33·6), 32·3% (-2·7 to 67·3), and 83·9% (47·2 to 120·7), respectively. Adjusting for parental education and single parent status moderately attenuated these estimates. INTERPRETATION: Early childhood disadvantage is more strongly correlated with multiple adolescent adversities than any of the five single adverse outcomes. However, shifting children from the lowest income quintile group to the next lowest group is ineffective. Tackling multiple adolescent adversities requires managing early childhood disadvantage across the social gradient, with income redistribution as a central element of coordinated cross-sectoral action. FUNDING: UK Prevention Research Partnership.

Age of First Overweight and Obesity, COVID-19 and Long COVID in Two British Birth Cohorts.

Longer exposure to obesity, and thus a longer period in an inflamed state, may increase susceptibility to infectious diseases and worsen severity. Previous cross-sectional work finds higher BMI is related to worse COVID-19 outcomes, but less is known about associations with BMI across adulthood. To examine this, we used body mass index (BMI) collected through adulthood in the 1958 National Child Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Participants were grouped by the age they were first overweight (> 25 kg/m2) and obese (> 30 kg/m2). Logistic regression was used to assess associations with COVID-19 (self-reported and serology-confirmed), severity (hospital admission and contact with health services) and long-COVID reported at ages 62 (NCDS) and 50 (BCS70). An earlier age of obesity and overweight, compared to those who never became obese or overweight, was associated with increased odds of adverse COVID-19 outcomes, but results were mixed and often underpowered. Those with early exposure to obesity were over twice as likely in NCDS (odds ratio (OR) 2.15, 95% confidence interval (CI) 1.17-4.00) and three times as likely in BCS70 (OR 3.01, 95% CI 1.74-5.22) to have long COVID. In NCDS they were also over four times as likely to be admitted to hospital (OR 4.69, 95% CI 1.64-13.39). Most associations were somewhat explained by contemporaneous BMI or reported health, diabetes or hypertension; however, the association with hospital admission in NCDS remained. An earlier age of obesity onset is related to COVID-19 outcomes in later life, providing evidence of the long-term impact of raised BMI on infectious disease outcomes in midlife.

Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher levels of SARS-CoV-2 anti-Spike antibodies are known to be associated with increased protection against future SARS-CoV-2 infection. However, variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination have not been explored across a wide range of socio-demographic, SARS-CoV-2 infection and vaccination, and health factors within population-based cohorts. Methods: Samples were collected from 9361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies and tested for SARS-CoV-2 antibodies. Cross-sectional sampling was undertaken jointly in April-May 2021 (TwinsUK, N=4256; ALSPAC, N=4622), and in TwinsUK only in November 2021-January 2022 (N=3575). Variation in antibody levels after first, second, and third SARS-CoV-2 vaccination with health, socio-demographic, SARS-CoV-2 infection, and SARS-CoV-2 vaccination variables were analysed. Using multivariable logistic regression models, we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection, and SARS-CoV-2 vaccination variables. Results: Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had threefold greater odds of SARS-CoV-2 infection over the next 6-9 months (OR = 2.9, 95% CI: 1.4, 6.0), compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK 'Shielded Patient List' had consistently greater odds (two- to fourfold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations. Conclusions: These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies. Funding: Antibody testing was funded by UK Health Security Agency. The National Core Studies program is funded by COVID-19 Longitudinal Health and Wellbeing - National Core Study (LHW-NCS) HMT/UKRI/MRC ([MC_PC_20030] and [MC_PC_20059]). Related funding was also provided by the NIHR 606 (CONVALESCENCE grant [COV-LT-0009]). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The UK Medical Research Council and Wellcome (Grant ref: [217065/Z/19/Z]) and the University of Bristol provide core support for ALSPAC.

Vaccination against the virus that causes COVID-19 triggers the body to produce antibodies that help fight future infections. But some people generate more antibodies after vaccination than others. People with lower levels of antibodies are more likely to get COVID-19 in the future. Identifying people with low antibody levels after COVID-19 vaccination is important. It could help decide who receives priority for future vaccination. Previous studies show that people with certain health conditions produce fewer antibodies after one or two doses of a COVID-19 vaccine. For example, people with weakened immune systems. Now that third booster doses are available, it is vital to determine if they increase antibody levels for those most at risk of severe COVID-19. Cheetham et al. show that a third booster dose of a COVID-19 vaccine boosts antibodies to high levels in 90% of individuals, including those at increased risk. In the experiments, Cheetham et al. measured antibodies against the virus that causes COVID-19 in 9,361 individuals participating in two large long-term health studies in the United Kingdom. The experiments found that UK individuals advised to shield from the virus because they were at increased risk of complications had lower levels of antibodies after one or two vaccine doses than individuals without such risk factors. This difference was also seen after a third booster dose, but overall antibody levels had large increases. People who received the Oxford/AstraZeneca vaccine as their first dose also had lower antibody levels after one or two doses than those who received the Pfizer/BioNTech vaccine first. Positively, this difference in antibody levels was no longer seen after a third booster dose. Individuals with lower antibody levels after their first dose were also more likely to have a case of COVID-19 in the following months. Antibody levels were high in most individuals after the third dose. The results may help governments and public health officials identify individuals who may need extra protection after the first two vaccine doses. They also support current policies promoting booster doses of the vaccine and may support prioritizing booster doses for those at the highest risk from COVID-19 in future vaccination campaigns.

Characterising patterns of COVID-19 and long COVID symptoms: evidence from nine UK longitudinal studies.

Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups ('no COVID-19', 'COVID-19 in last 12 weeks', 'COVID-19 > 12 weeks ago'), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 'COVID-19 in last 12 weeks' and 'no COVID-19' groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 'COVID-19 > 12 weeks ago' and 'no COVID-19' groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.

Socioeconomic and sex inequalities in parent-reported adolescent mental ill-health: time trends in four British birth cohorts.

BACKGROUND: Studies using symptom-based screeners have suggested that mental ill-health has increased in adolescents in recent decades, however, few studies have tested the equivalence of their instruments, which is critical for inferring changes in prevalence. In addition, little research has explored whether socioeconomic position (SEP) and sex inequalities in adolescent mental health have changed over time. METHODS: Using structural equation modelling, we explored SEP and sex differences in harmonised parent reports of emotional and behavioural problems, using data from four UK birth cohorts: the 1958 National Child Development Study (NCDS'58; n = 10,868), the 1970 British Cohort Study (BCS'70; n = 8,242), the 1991-92 Avon Longitudinal Study of Parents and Children (ALSPAC'91; n = 5,389), and the 2000-01 Millennium Cohort Study (MCS'01; n = 9,338). RESULTS: Compared with the two earliest cohorts, members of MCS'01 had higher latent mean scores on emotional problems (both sexes), and lower scores on behavioural problems (females only). The associations between four indicators of SEP and emotional problems were strongest in MCS'01, with housing tenure having the strongest association. All four SEP indicators were associated with behavioural problems in each cohort, with housing tenure again more strongly associated with problems in the MCS'01. Mediation analyses suggested that the increase in emotional problems occurred despite broadly improving socioeconomic conditions. CONCLUSIONS: Our findings suggest that parent reports of adolescent emotional problems, but not behavioural problems, have risen in recent generations and this trend is not solely due to reporting styles. A failure to address widening social inequalities may result in further increases in mental ill-health amongst disadvantaged young people.