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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.

Introduction Breast cancer is the leading cause of cancer-related deaths among women worldwide. In Costa Rica, it ranks first in incidence and fourth in terms of mortality. However, there is a lack of comprehensive information on treatment patterns and outcomes for breast cancer patients in Costa Rica. Methods This study utilized data from the National Tumor Registry, which was merged with the Costa Rica Social Security Fund (CCSS) to ensure comprehensive access to clinical information. The study is prospective and focused on patients diagnosed with breast cancer between January 2008 and December 2012. This combined dataset allowed for a more comprehensive analysis of patient characteristics, treatment patterns, and outcomes related to breast cancer in Costa Rica. Results Among the 4775 patients diagnosed during this period, 3160 met the inclusion criteria for our study. The average age at diagnosis was 59.1 years, with 32.5% of patients being over the age of 65. Most of the patients (55.4%) identified themselves as homemakers, while 46.5% underwent core needle biopsy for diagnosis. Approximately 60% of women were diagnosed with early-stage disease (IA, IIA, and IIB), while 1.7% had metastatic disease, mainly affecting the bone. The mean interval between diagnosis and surgery was 72 days. Most patients (88.7%) received surgery as their initial treatment, and over half (54.4%) received some form of adjuvant therapy. Additionally, 85.6% of patients completed their prescribed treatment. Conclusion This study provides a comprehensive and detailed description of the characteristics and treatment patterns among breast cancer patients in Costa Rica. The findings contribute to our understanding of the disease in this population and can serve as a foundation for further research and improvement in breast cancer management and care.

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.

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.

Introduction Variability in household secondary attack rates and transmission risks factors of SARS-CoV-2 remain poorly understood. Methods We conducted a household transmission study of SARS-CoV-2 in Costa Rica, with SARS-CoV-2 index cases selected from a larger prospective cohort study and their household contacts were enrolled. A total of 719 household contacts of 304 household index cases were enrolled from November 21, 2020, through July 31, 2021. Blood specimens were collected from contacts within 30–60 days of index case diagnosis; and serum was tested for presence of spike and nucleocapsid SARS-CoV-2 IgG antibodies. Evidence of SARS-CoV-2 prior infections among household contacts was defined based on the presence of both spike and nucleocapsid antibodies. We fitted a chain binomial model to the serologic data, to account for exogenous community infection risk and potential multi-generational transmissions within the household. Results Overall seroprevalence was 53% (95% confidence interval (CI) 48–58%) among household contacts. The estimated household secondary attack rate is 34% (95% CI 5–75%). Mask wearing by the index case is associated with the household transmission risk reduction by 67% (adjusted odds ratio = 0.33 with 95% CI: 0.09–0.75) and not sharing bedroom with the index case is associated with the risk reduction of household transmission by 78% (adjusted odds ratio = 0.22 with 95% CI 0.10–0.41). The estimated distribution of household secondary attack rates is highly heterogeneous across index cases, with 30% of index cases being the source for 80% of secondary cases. Conclusions Modeling analysis suggests that behavioral factors are important drivers of the observed SARS-CoV-2 transmission heterogeneity within the household. Plain Language Summary When living in the same house with known SARS-CoV-2 cases, household members may change their behavior and adopt preventive measures to reduce the spread of SARS-CoV-2. To understand how behavioral factors affect SARS-CoV-2 spreading in household settings, we focused on household members of individuals with laboratory-confirmed SARS-CoV-2 infections and followed the way SARS-CoV-2 spread within the household, by looking at who had antibodies against the virus, which means they were infected. We also asked participants detailed questions about their behavior and applied mathematical modeling to evaluate its impact on SARS-CoV-2 transmission. We found that mask-wearing by the SARS-CoV-2 cases, and avoiding sharing a bedroom with the infected individuals, reduces SARS-CoV-2 transmission. However, caring for SARS-CoV-2 cases, and prolonged interaction with infected individuals facilitate SARS-CoV-2 spreading. Our study helps inform what behaviors can help reduce SARS-CoV-2 transmission within a household. Sun et al. investigate SARS-CoV-2 household transmission in a cohort in Costa Rica assessing behavioral factors and preventive measures. They show that behavioral factors are significant drivers of SARS-CoV-2 transmission in the household setting.