Percorrer por autor "Afreixo, Vera"
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- Development and Application of a Harmonization Method for IgG Antibody Levels Against SARS-CoV-2S pike Protein: A Cohort Study in Healthcare ProfessionalsPublication . Saraiva, Ana Leonor; Afreixo, Vera; Gaio, Vânia; Machado, AusendaIntroduction: The emergence of COVID-19 led to the rapid development of vaccines and diagnostic tests. To assess antibody responses in healthcare workers (HCWs), a 2021–2022 cohort study was conducted in three Portuguese hospitals. Antibody levels were measured at six time points: pre-vaccination, post-first dose, at 3, 6, 12 months after the second dose, and post-booster. Each hospital utilized a different assay: Abbott’s CMIA, Roche’s Elecsys® ECLIA, and Siemens’ ADVIA Centaur®, leading to challenges in data comparability. The study aimed to harmonize serological data across these hospitals to enable joint analysis and better understand the dynamics of humoral immunity among HCWs in Portugal. Methods: To ensure adequate conversion of antibody titers obtained from different laboratory methods, several harmonization strategies were applied and compared. These included the World Health Organization (WHO) international conversion and a main strategy based on quantile interpolation, with linear and spline methods tested, followed by Deming regression. Before interpolation, models were required to estimate the antibody titers due to the limitations of each method, such as linear regressions with polynomials and splines, followed by data linearization and normalization. The final choice between methods was based on a graphical assessment of which approach best preserved the original data patterns prior to harmonization. Results: The application of quantile interpolation followed by regression proved more effective than the WHO recommended approach for harmonizing data across hospitals. This method preserved the individual distribution patterns of each hospital, even after transformation. Importantly, it allowed the harmonized values to reflect the scale and magnitude observed in the reference method (Abbott’s CMIA). After harmonization, a marked increase was observed between the pre-vaccination time point and the post-vaccination time point, followed by a gradual decrease over the next three time points. Finally, a second, even more pronounced increase was observed after the booster dose. Conclusions: Quantile interpolation followed by regression enabled effective harmonization of serological data across the hospital centers, allowing for the comparison and joint analysis of anti-SARS-CoV-2 IgG antibody titers from different laboratory methods. This approach also preserved the expected temporal antibody response pattern. Although laboratory validation, by quantifying the same samples across different laboratories, was not performed, which would be necessary to fully confirm the adequacy of the method, the presented methodology shows strong applicability to other contexts, particularly in European studies that conduct pooled analyses of data from multiple countries and laboratories.
- Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferationPublication . Bernardo, Carina; Santos, Júlio; Costa, Céu; Tavares, Ana; Amaro, Teresina; Marques, Igor; Gouveia, Maria João; Félix, Vítor; Afreixo, Vera; Brindley, Paul J.; Costa, José Manuel; Amado, Francisco; Helguero, Luisa; Santos, Lúcio L.Estrogen-like metabolites have been identified in S. haematobium, the helminth parasite that causes urogenital schistosomiasis (UGS) and in patients´ blood and urine during UGS. Estrogen receptor (ER) activation is enriched in the luminal molecular subtype bladder cancer (BlaCa). To date, the significance of ER to these diseases remains elusive. We evaluated ERα and ERβ expression in UGS-related BlaCa (n = 27), UGS-related non-malignant lesions (n = 35), and noninfected BlaCa (n = 80). We investigated the potential of ERα to recognize S. haematobium-derived metabolites by docking and molecular dynamics simulations and studied ERα modulation in vitro using 3 BlaCa cell lines, T24, 5637 and HT1376. ERα was expressed in tumor and stromal cells in approximately 20% noninfected cases and in 30% of UGS-related BlaCa, predominantly in the epithelial cells. Overall, ERα expression was associated with features of tumor aggressiveness such as high proliferation and p53 positive expression. ERα expression correlated with presence of schistosome eggs. ERβ was widely expressed in both cohorts but weaker in UGS-related cases. molecular dynamics simulations of the 4 most abundant S. haematobium-derived metabolites revealed that smaller metabolites have comparable affinity for the ERα active state than 17β-estradiol, while the larger metabolites present higher affinity. Our in vitro findings suggested that ERα activation promotes proliferation in ERα expressing BlaCa cells and that this can be reverted with anti-estrogenic therapy. In summary, we report differential ER expression between UGS-related BlaCa and noninfected BlaCa and provide evidence supporting a role of active ERα during UGS and UGS-induced carcinogenesis.
- Impacto da COVID-19 na incidência de hospitalizações por lesões autoinfligidas em PortugalPublication . Cardoso, Catarina; Silva, Susana; Alves, Tatiana; Nunes, Baltazar; Afreixo, VeraCom o início da pandemia de COVID-19, a realidade até então conhecida mudou para muitas pessoas. A falta de convivência com familiares e amigos, insegurança, ansiedade, medo de contrair a infeção, problemas económicos decorrentes da pandemia e luto pelos familiares e amigos que perderam e dos quais não se puderam despedir devido às restrições, podem aumentar os riscos para a saúde mental e consequentemente para lesões autoinfligidas e até suicídio. O objetivo deste estudo é conhecer o o impacto de 19 meses de COVID-19, desde março de 2020 a setembro de 2021, na incidência mensal de hospitalizações por lesões autoinfligidas em Portugal. quando comparado com o período de 32 meses pré-pandémicos, desde julho de 2017 a fevereiro de 2020. Os dados sobre a ocorrência de hospitalizações são provenientes da base de dados de morbilidade hospitalar da ACSS e os denominadores populacionais para o cálculo da taxa de incidência foram obtidos do INE. Foi realizada uma análise descritiva dos dados e decomposta a série temporal pela sazonalidade e tendência. Para a comparação das tendências nos dois períodos foi aplicada uma análise de séries temporais interrompidas cuja intervenção considerada foi o mês de março de 2020 em que houve o primeiro caso de COVID-19 registado em Portugal. Foi realizada também uma análise de correlação entre o número de hospitalizações por lesões autoinfligidas e a duração nos locais de residência. A taxa de incidência mensal de hospitalizações por lesões autoinfligidas por 100 000 habitantes no período total em análise é de 2.77, no período pré-pandémico é de 2.93 e no período pandémico é de 2.49 hospitalizações, verificando-se uma diminuição de 0.45 Verificou-se um padrão sazonal, apresentando o mês de dezembro valores inferiores aos restantes meses do respetivo ano. No período pré-pandémico o número de hospitalizações apresentava uma tendência ligeiramente decrescente, com uma diminuição de 0.09% a cada mês. Quando a pandemia iniciou verificou-se uma diminuição do nível de 69.27% e uma alteração da tendência para crescente, aumentando 2.13% a cada mês. Verificou-se que o número de hospitalizações é menor quando há uma maior permanência nos locais de residência, ou seja, existe uma correlação negativa de -0.65 estatisticamente significativa (valor-p= 0.002). Nesta análise verificou-se com o início da pandemia uma diminuição acentuada das hospitalizações por lesões autoinfligidas, que ao longo do tempo parece retomar a tendência pré-pandémica
- Linear Regression Analysis of Harmonized IgG Antibody Levels Against the SARS-CoV-2 Spike Protein: A Cohort Study in Healthcare WorkersPublication . Saraiva, Ana Leonor; Afreixo, Vera; Machado, Ausenda; Gaio, VâniaThe emergence of COVID-19 in 2019 led to the rapid development of vaccines and diagnostic tests. To assess antibody responses in healthcare workers (HCWs), a cohort study was conducted between 2021 and 2022 across three Portuguese hospitals. Antibody levels were measured at six time points: prevaccination, post-vaccination, and at 3, 6, and 12 months after the vaccination, as well as after the booster dose. Each hospital used a different assay: Abbott’s CMIA, Roche’s Elecsys® ECLIA, and Siemens’ ADVIA Centaur®, posing challenges for data comparability. The study aimed to harmonize serological data across these hospitals and to model antibody increases and decreases over time using linear regression. To ensure adequate conversion of antibody titers from different laboratory methods, quantile harmonization, and Deming regression were applied. After harmonization, three linear regressions were fitted: one for the increase between prevaccination and post-vaccination, another for the decrease between post-accination and 12 months after vaccination, and finally, one for the increase between 12 months after vaccination and after the booster dose. Models included variables such as prior infection, age, hospital, smoking status, contact with COVID-19 patients, and chronic conditions. In the phase-specific analysis, in addition to variations between hospitals in the regression of the last increase after the booster dose, it was observed that individuals over 50 years of age exhibited a superior immune response (811 550; IC 95%: 598 774, 1 024 327; p < 0.001). This higher percentage increase may be explained by initially lower levels, unlike younger individuals who had higher titers.
- Longitudinal dynamics of humoral immunity among health care workers in Portugal using mixed effects modellingPublication . Saraiva, Ana Leonor; Afreixo, Vera; Machado, Ausenda; Gaio, VâniaIntroduction: The emergence of COVID-19 in 2019 led to the rapid development of vaccines and diagnostic tests. To assess antibody responses in healthcare workers (HCWs), a 2021–2022 cohort study was conducted across three Portuguese hospitals. Antibody levels were measured at six intervals: pre-vaccination, post-first dose, at 3, 6, and 12 months after the second dose, and post-booster. Each hospital utilized a different assay: Abbott’s CMIA,, Roche’s Elecsys® ECLIA, and Siemens’ ADVIA Centaur®, leading to challenges in data comparability. The study aimed to harmonize serological data across these hospitals and, through mixed-effects modeling, jointly analyze the longitudinal dynamics of humoral immunity among HCWs in Portugal. Methods: To ensure adequate conversion of antibody titers from different laboratory methods, quantile harmonization, and Deming regression were applied. After harmonization, linear mixed-effects models (LMER) assessed the relationship between antibody levels and covariates, accounting for fixed and random effects. The models included variables such as prior infection, age, hospital, smoking status, contact with COVID-19 patients, and chronic conditions. Sensitivity analyses included models excluding outliers, removing influential points, and applying multiple imputation for missing data. Results: The mixed-effects models demonstrated significant increases in antibody levels following vaccination (β = 21,234; 95% CI: 14,014–28,454; p < 0.001), with an even greater rise observed after the booster dose (β = 33,185; 95% CI: 25,939–40,430; p < 0.001) when compared to the pre-vaccination baseline. Significant differences between hospitals were also evident, as Roche’s Elecsys® ECLIA showed a notably smaller increase at 3 months compared to Abbott’s CMIA (β = -3,285; 95% CI: -5,511 to -1,058; p = 0.004). Interaction plots highlighted how covariates influenced antibody levels over time, revealing higher antibody responses post-vaccination and booster among individuals with prior infection, younger age groups, non-smokers, healthcare workers with direct patient contact, and those without chronic conditions. Sensitivity analyses, such as removing outliers and influential points and applying multiple imputation for missing data, confirmed the robustness and reliability of these findings. Conclusions: The harmonization of antibody measurements enabled a clear evaluation of immune response dynamics among healthcare workers. Vaccination and booster doses significantly increased antibody levels, while differences between hospitals and individual characteristics influenced the magnitude of these responses. These findings enhance our understanding of factors shaping humoral immunity and may guide future vaccination strategies.