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Allostatic load (AL) is a measure of overall physiological wear-and-tear over the life course, which could partially be the consequence of early life exposures. AL could allow a better understanding of the potential biological pathways playing a role in the construction of the social gradient in adult health. To explore the biological embedding hypothesis, we examined whether adverse childhood experiences (ACEs) are associated with elevated AL in midlife. We used imputed data on 3,782 women and 3,753 men of the National Child Development Study in Britain followed up seven times. ACEs were measured using prospective data collected at ages 7, 11, and 16. AL was operationalized using data from the biomedical survey collected at age 44 on 14 parameters representing four biological systems. We examined the role of adult health behaviors, body mass index (BMI), and socioeconomic status as potential mediators using a path analysis. ACEs were associated with higher AL for both men and women after adjustment for early life factors and childhood pathologies. The path analysis showed that the association between ACEs and AL was largely explained by early adult factors at age 23 and 33. For men, the total mediated effect was 59% (for two or more ACEs) via health behaviors, education level, and wealth. For women, the mediated effect represented 76% (for two or more ACEs) via smoking, BMI, education level, and wealth. Our results indicate that early psychosocial stress has an indirect lasting impact on physiological wear-and-tear via health behaviors, BMI, and socioeconomic factors in adulthood.

Previous SARS-CoV-2 research indicates that antibody levels and corresponding neutralization potential increase with additional exposures (comprising vaccination or infection), and that hybrid immunity resulting from combined vaccination and natural infection is more robust than either alone. However, it is unclear whether or how antibody levels increase or eventually plateau with repeated exposures and how SARS-CoV-2 exposure differs by sex or other demographic factors. Research regarding the association of antibody production with neutralization potential is also limited. We conducted this analysis within the RESPIRA population-based cohort in Costa Rica to investigate relationships between antibody levels and neutralization potential at increasing exposure levels. We examined immunological profiles from systematically defined single-exposure groups (one vaccine dose or one natural infection), double-exposure groups (two vaccine doses or one vaccine dose following a natural infection), and a triple-exposure group (two vaccine doses following a natural infection). We used a S1-RBD-based serological assay for antibody level detection and a pseudovirion assay for neutralization potential quantification. Using linear regression, we compared antibody levels and pseudoneutralization geometric mean titers between exposure groups. For single exposure groups, one vaccine dose was inferior to natural infection, but a second vaccine dose was superior to natural infection. For double exposure groups, those who were vaccinated once after infection developed higher levels of antibodies and higher neutralization potential compared with those who had only two vaccine doses. We note that peak antibody levels following an exposure may plateau after two exposures while neutralization potential continues to increase with a third exposure dose. Response patterns were comparable in males and females and in sensitivity analyses stratified by age, vaccine type, and pandemic wave. These results provide evidence that SARS-CoV-2 vaccination after COVID infection provides immunological benefit and suggest neutralization potential continues to increase after a second vaccine dose despite plateauing of antibody levels.

SummaryBackgroundIn 2022, WHO recommended single-dose human papillomavirus (HPV) vaccination as an alternative schedule to multidose regimens. To provide evidence to support approval of a single-dose indication for the AS04-adjuvanted bivalent HPV vaccine (Cervarix, GlaxoSmithKline), we investigated whether the immune response to a single dose of the bivalent vaccine in girls aged 9–14 years was non-inferior to the immune response to three doses of the quadrivalent HPV vaccine (Gardasil-4, Merck) in women aged 18–25 years, a dose and population combination with demonstrated efficacy. MethodsThis non-randomised, open-label, immunobridging trial enrolled girls aged 9–14 years and women aged 18–25 years in Guanacaste Province, Costa Rica. Healthy girls aged 9–14 years received one dose of bivalent HPV vaccine, whereas healthy women aged 18–25 years received three doses of quadrivalent HPV vaccine at 0, 2, and 6 months. The primary endpoint was geometric mean concentrations (GMCs) of HPV-specific serum antibodies measured by a validated virus-like-particle-based ELISA assay at 36 months. The per-protocol cohort included participants who received the correct number of doses within the predefined vaccination windows, had blood collected at the 36-month study visit for the final analysis, were seronegative at baseline for the specified HPV type, and did not receive additional HPV vaccine doses outside the study. Non-inferiority was declared when the lower bound of the 96% CI for the GMC ratio was greater than or equal to 0·67 for HPV-16 and HPV-18. Seropositivity was a secondary objective. Safety was analysed in the total vaccinated population. This trial is registered with ClinicalTrials.gov, NCT03728881, and is complete. FindingsBetween April 1 and Aug 16, 2019, 620 girls and 620 women were enrolled and received their first HPV vaccination. After exclusions, 539 girls and 366 women were HPV-16 seronegative at enrolment and were included in the HPV-16 per-protocol cohort; 523 girls and 373 women were HPV-18 seronegative at enrolment and were included in the HPV-18 per-protocol cohort. At 36 months, the HPV-16 GMC was 21·4 international units (IU)/mL (95% CI 19·7–23·3) in girls in the single-dose bivalent vaccine group and 42·9 IU/mL (95% CI 38·9–47·3) in women in the three-dose quadrivalent vaccine group, resulting in a GMC ratio of 0·50 (96% CI 0·44–0·57); the HPV-18 GMC was 8·0 IU/mL (95% CI 7·4–8·8) in girls in the single-dose bivalent vaccine group and 7·2 IU/mL (95% CI 6·4–8·1) in women in the three-dose quadrivalent vaccine group, resulting in a GMC ratio of 1·11 (96% CI 0·95–1·29). At 36 months, 538 (99·8%, 95% CI 99·1–100) of 539 girls in the single-dose bivalent vaccine group were seropositive for HPV-16 compared with 366 (100%, 99·2–100) of 366 women in the three-dose quadrivalent vaccine group (p=1·00). The proportion of participants who were seropositive for HPV-18 was higher in the single-dose bivalent vaccine group (517 [98·9%, 95% CI 97·6–99·5] of 523 girls) than in the three-dose quadrivalent vaccine group (358 [96·0%, 93·6–97·6] of 373 women; p=0·0065). Two serious adverse events were reported in 620 girls and 13 serious adverse events were reported in 620 women; all serious adverse events were deemed to be unrelated to HPV vaccination. InterpretationNon-inferior antibody responses for the single-dose bivalent HPV vaccine were seen for HPV-18 but not HPV-16, which would be insufficient evidence to motivate regulatory change, even though seropositivity approached 100% in the follow-up phase and the observed antibody concentrations were similar to protective levels seen in previous trials. Trials that directly evaluate protection afforded by single-dose HPV vaccination against persistent HPV infection will definitively address the level of protection afforded by single-dose HPV vaccination. FundingNational Cancer Institute, Cancer Research UK, and the Gates Foundation. TranslationFor the Spanish translation of the abstract see Supplementary Materials section.

Antibodies to SARS-CoV-2 are essential for protection or reduction in severity of subsequent disease. We studied antibody responses to spike protein receptor-binding domain (S1-RBD) and nucleocapsid (N) in a population-based sample of COVID-19 cases in Costa Rica. As part of the RESPIRA study, we selected an age-stratified random sample of PCR-confirmed COVID-19 cases diagnosed from March 2020 to July 2021. Antibodies were determined with multiplex serology in 794 unvaccinated subjects diagnosed 3 days to 17 months before recruitment to investigate immune response to natural infection. In addition, neutralizing antibodies were determined in 136 randomly selected participants. We estimated antibody positivity and GMTs by time since diagnosis and explored determinants using multivariate regression. Most participants tested 15-29 days after PCR diagnosis were seropositive for N (90%) and S1-RBD antibodies (96%) and had the highest GMTs for both antibodies. Only 42% of subjects tested one year after infection were seropositive for N antibodies, compared to 97% for S1-RBD. GMTs for neutralizing antibodies peaked 15-89 days after infection and declined but remained positive for 95% of subjects thereafter. In multivariate models, antibodies were significantly higher among men and increased with age and severity of the clinical presentation. The correlation of multiplex and neutralizing antibodies was high (0.72 [95% CI = 0.63-0.79]) and stronger among women. A robust immune response against N and S1-RBD is elicited by COVID-19 a few days after infection. While S1-RBD antibodies are present after > 1 year, N antibodies decline significantly. Antibody levels are higher in men and increase with age and severity of disease. The different immune response patterns by sex warrant further investigation. RESPIRA Study ClinicalTrials.gov ID: NCT04537338 (3 September 2020).

Background Evidence continues to accumulate regarding the potential long-term health consequences of COVID-19 in the population. To distinguish between COVID-19-related symptoms and health limitations from those caused by other conditions, it is essential to compare cases with community controls using prospective data ensuring case-control status. The RESPIRA study addresses this need by investigating the lasting impact of COVID-19 on Health-related Quality of Life (HRQoL) and symptomatology in a population-based cohort in Costa Rica, thereby providing a robust framework for controlling HRQoL and symptoms. Methods The study comprised 641 PCR-confirmed, unvaccinated cases of COVID-19 and 947 matched population-based controls. Infection was confirmed using antibody tests on enrollment serum samples and symptoms were monitored monthly for 6 months post-enrolment. Administered at the 6-month visit (occurring between 6- and 2-months post-diagnosis for cases and 6 months after enrollment for controls), HRQoL and Self-Perceived Health Change were assessed using the SF-36, while brain fog, using three items from the Mental Health Inventory (MHI). Regression models were utilized to analyze SF-36, MHI scores, and Self-Perceived Health Change, adjusted for case/control status, severity (mild case, moderate case, hospitalized) and additional independent variables. Sensitivity analyses confirmed the robustness of the findings. Results Cases showed significantly higher prevalences of joint pain, chest tightness, and skin manifestations, that stabilized at higher frequencies from the fourth month post-diagnosis onwards (2.0%, 1.2%, and 0.8% respectively) compared to controls (0.9%, 0.4%, 0.2% respectively). Cases also exhibited significantly lower HRQoL than controls across all dimensions in the fully adjusted model, with a 12.4 percentage-point difference [95%CI: 9.4-14.6], in self-reported health compared to one year prior. Cases reported 8.0% [95%CI: 4.2, 11.5] more physical limitations, 7.3% [95%CI: 3.5, 10.5] increased lack of vitality, and 6.0% [95%CI: 2.4, 9.0] more brain fog compared to controls with similar characteristics. Undiagnosed cases detected with antibody tests among controls had HRQoL comparable to antibody negative controls. Differences were more pronounced in individuals with moderate or severe disease and among women. Conclusions PCR-confirmed unvaccinated cases experienced prolonged HRQoL reductions 6 months to 2 years after diagnosis, this was particularly the case in severe cases and among women. Mildly symptomatic cases showed no significant long-term sequelae.

This research investigates the influence of place of residence and diabetic patient's socioeconomic position on their use of health services in a universal health care system. This retrospective cross-sectional population-based study is based on the joint use of the Health Insurance information systems, an ecological indicator of social deprivation and an indicator of potential spatial accessibility of healthcare provision in the Midi-Pyrénées region. Using French healthcare insurance population-based data on reimbursement of out-of-hospital care during the year 2012, we study the use of health services among patients aged 50 and over (n = 90,136).We built logistic regression models linking health services use to socioeconomic position by geographic area, adjusted for age, gender, healthcare provision, information regarding patients precariousness, and long-term condition, used as proxy for the state of health. After adjustment for healthcare provision, the lower population density in the geographical area of concern, the lower the access to specialised care, independent of the patients' SEP. General practitioner attendance was higher among the patients with the lowest SEP without being clearly influenced by their living place. We found no clear influence of either patients' SEP or their living place on their access to biological follow-up. This study is an attempt to account for the geographical context and to go further in studying the social determinants of health among diabetes patients.

PurposeThe RESPIRA cohort aims to describe the nature, magnitude, time course and efficacy of the immune response to SARS-CoV-2 infection and vaccination, population prevalence, and household transmission of COVID-19.ParticipantsFrom November 2020, we selected age-stratified random samples of COVID-19 cases from Costa Rica confirmed by PCR. For each case, two population-based controls, matched on age, sex and census tract were recruited, supplemented with hospitalised cases and household contacts. Participants were interviewed and blood and saliva collected for antibodies and PCR tests. Participants will be followed for 2 years to assess antibody response and infection incidence.Findings to dateRecruitment included 3860 individuals: 1150 COVID-19 cases, 1999 population controls and 719 household contacts from 304 index cases. The age and regional distribution of cases was as planned, including four age strata, 30% rural and 70% urban. The control cohort had similar sex, age and regional distribution as the cases according to the study design. Among the 1999 controls recruited, 6.8% reported at enrolment having had COVID-19 and an additional 12.5% had antibodies against SARS-CoV-2. Compliance with visits and specimens has been close to 70% during the first 18 months of follow-up. During the study, national vaccination was implemented and nearly 90% of our cohort participants were vaccinated during follow-up.Future plansRESPIRA will enable multiple analyses, including population prevalence of infection, clinical, behavioural, immunological and genetic risk factors for SARS-CoV-2 acquisition and severity, and determinants of household transmission. We are conducting retrospective and prospective assessment of antibody levels, their determinants and their protective efficacy after infection and vaccination, the impact of long-COVID and a series of ancillary studies. Follow-up continues with bimonthly saliva collection for PCR testing and biannual blood collection for immune response analyses. Follow-up will be completed in early 2024.Trial registration numberNCT04537338.

Background: A global pandemic due to COVID-19 emerged in November 2019 and hit France in early March 2020. It not only resulted in a loss of lives, but also in very strict confinement measures. The objective of this study was to understand what the determinants of the changes in participants’ behavior and mental state were during the confinement. Methods: An online survey was launched on 23 April 2020 and closed on 7 May 2020. The final sample included 1454 participants from 24 to 65 years old. Descriptive and multivariate analyses were then performed. Results: In total, 28.7% reported having a more balanced diet, against 17.1% with a less balanced diet, 22.7% of respondents reported an increased alcohol consumption, as opposed to only 12.2% declaring a decrease, and 11.2% of respondents increased their tobacco consumption, while 6.3% decreased it. In total, 50.6% of the participants reported being more depressed, stressed, or irritable since the beginning of the lockdown. Confinement had a negative effect on every behavior studied in this survey, except for nutrition. We also found that negative mental state changes were strongly associated with nutrition, sleep, physical activity and alcohol consumption changes.

Introduction: Measuring socioeconomic position (SEP) is central in the analysis of social inequalities in health (SIH). It requires the use of updated instruments, adapted to a particular conceptual framework, taking into account the local context and the population characteristics. This study aims to present and discuss the advantages and disadvantages of different measurement of SEP used in Costa Rica for the analysis of health inequalities.  Materials and methods: A systematic review of the existing instruments and methods used to characterize SEP in Costa Rica was carried out. Results: There is a great diversity of instruments used as proxies of SEP in Costa Rica, both at the individual, and at geographical level. These measures allow to capture specific dimensions of SEP potentially associated with different health outcomes. Being a latent concept, variables approaching SEP should refer to their specific conceptual framework, be adapted to the study design, and population’s characteristics (e.g. age), and should consider the study feasibility of data collection.  Due to the variety and different conceptual frameworks behind each SEP variable, it is not possible to establish the existence of a gold standard. Conclusion: This review of the Costa Rican health inequalities literature regarding SEP instruments, can contribute to a better use of the existing tools. It will allow researchers to better evaluate the instruments that have been previously validated, their respective theoretical frameworks and limitations, to choose the most suitable proxy of SEP for the local context analyzed.

This article analyses the relationship between socio-economic status and the prevalence of overweight and obesity in the primary school population in Costa Rica. A National School Weight/Height Census was disseminated across Costa Rica in 2016. The percentage of children who were overweight or obese was calculated by sex, age and socio-economic indicators (type of institution: private, public, mix; type of geographic location: rural, urban and the level of development of the district of residence: quartiles). A mixed-effects multinomial logistic regression model and mixed-effects logistic regression model were used to analyse the association between the prevalence of being overweight or obese and district socio-economic status. The survey was carried out in public and private primary schools across Costa Rica in 2016. In total, 347 366 students from 6 to 12 years were enrolled in public and private primary schools. The prevalence of overweight and obesity among children was 34·0 %. Children in private schools were more likely to be overweight or obese than students in public schools (OR = 1·10 [1·07, 1·13]). Additionally, children were less likely to be overweight or obese if attending a school in a district of the lowest socio-economic quartile compared with the highest socio-economic quartile (OR = 0·79 [0·75, 0·83]) and in a rural area compared with the urban area (OR = 0·92 [0·87, 0·97]). Childhood obesity in Costa Rica continues to be a public health problem. Prevalence of overweight and obesity in children was associated with indicators of higher socio-economic status.