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Sociodemographic, clinical, and immunological factors associated with SARS-CoV-2 diagnosis and severe COVID-19 outcomes in people living with HIV: a retrospective cohort study.
(Elsevier B.V., 2021-10-13) Cortés, C.; Force, L.; Letang, Emilio; Vilaró, I.; Casabona, J.; Miró Meda, José M. (José María), 1956-; PISCIS study group.; Nomah, D.K.; Reyes-Urueña, J.; Díaz, Y.; Moreno, Silvia; Aceiton, J.; Bruguera, A.; Vivanco-Hidalgo, R.M.; Llibre, J.M.; Domingo, Pere (Domingo Pedrol); Falcó, V.; Imaz, Arkaitz
Background: Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with HIV. Methods: We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis. Findings: We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0-52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31-1·83), men who have sex with men (1·42, 1·09-1·86), and those with four or more chronic comorbidities (1·46, 1·09-1·97). Age at least 75 years (5·2, 1·8-15·3), non-Spanish origin (2·1, 1·3-3·4), and neuropsychiatric (1·69, 1·07-2·69), autoimmune disease (1·92, 1·14-3·23), respiratory disease (1·84, 1·09-3·09), and metabolic disease (2·59, 1·59-4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15). Interpretation: People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes. Funding: Fundació "la Caixa". Translations: For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section.
Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers
(Elsevier, 2022-01-11) Moncunill, Gemma; Aguilar, Ruth; Ribes, Marta; Ortega, Natalia; Rubio, Rocío; Salmerón, Gemma; Molina, María José; Vidal, Marta; Barrios, Diana; Mitchell, Robert A.; Jiménez, Alfons; Castellana, Cristina; Hernández-Luis, Pablo; Rodó, Pau; Méndez, Susana; Llupià García, Anna; Puyol, Laura; Rodrigo Melero, Natalia; Carolis, Carlo; Mayor Aparicio, Alfredo Gabriel; Izquierdo, Luis; Varela, Pilar; Trilla Garcia, Antonio De Padua; Vilella, Anna; Barroso, Sonia; Angulo Aguado, Ana; Engel Rocamora, Pablo; Tortajada, Marta; Garcia-Basteiro, Alberto L.; Dobaño, Carlota, 1969-
Background: Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naïve adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. Methods: We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. Findings: Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects (p<0·05). A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with 43% (95% CI, 19-59) and 45% (95% CI, 63-18) lower neutralization, respectively, and 35% (95% CI, 3-57%) and 55% (95% CI, 33-70%) lower antibody levels, respectively. Among fully vaccinated, 6·3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. Interpretation: Our data support administering a single-dose in pre-exposed healthy individuals as primary vaccination. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination and in face of variants that escape immunity such as Omicron. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year. Funding: This work was supported by Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona, the Fundació Privada Daniel Bravo Andreu, and European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Programme. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L. I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.
RBD-Based ELISA and Luminex Predict Anti-SARS-CoV-2 Surrogate-Neutralizing Activity in Two Longitudinal Cohorts of German and Spanish Health Care Workers
(American Society for Microbiology, 2023-02-14) Aguilar, Ruth; Li, Xue; Crowell, Claudia S.; Burrell, Teresa; Vidal, Marta; Rubio, Rocío; Jiménez, Alfons; Hernández-Luis, Pablo; Hofmann, Dieter; Mijočević, Hrvoje; Jeske, Samuel; Christa, Catharina; D'Ippolito, Elvira; Lingor, Paul; Knolle, Percy A; Roggendorf, Hedwig; Priller, Alina; Yazici, Sarah; Carolis, Carlo; Mayor Aparicio, Alfredo Gabriel; Schreiner, Patrik; Poppert, Holger; Beyer, Henriette; Schambeck, Sophia E.; Izquierdo Lázaro, Luis; Tortajada, Marta; Angulo Aguado, Ana; Soutschek, Sophia E.; Engel Rocamora, Pablo; Garcia-Basteiro Alberto L.; Busch, Dirk H; Moncunill Piñas, Gemma; Protzer, Ulrike; Dobaño, Carlota, 1969- ; Gerhard, Markus
The ability of antibodies to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important correlate of protection. For routine evaluation of protection, however, a simple and cost-efficient anti-SARS-CoV-2 serological assay predictive of serum neutralizing activity is needed. We analyzed clinical epidemiological data and blood samples from two cohorts of health care workers in Barcelona and Munich to compare several immunological readouts for evaluating antibody levels that could be surrogates of neutralizing activity. We measured IgG levels against SARS-CoV-2 spike protein (S), its S2 subunit, the S1 receptor binding domain (RBD), and the full length and C terminus of nucleocapsid (N) protein by Luminex, and against RBD by enzyme-linked immunosorbent assay (ELISA), and assessed those as predictors of plasma surrogate-neutralizing activity measured by a flow cytometry assay. In addition, we determined the clinical and demographic factors affecting plasma surrogate-neutralizing capacity. Both cohorts showed a high positive correlation between IgG levels to S antigen, especially to RBD, and the levels of plasma surrogate-neutralizing activity, suggesting RBD IgG as a good correlate of plasma neutralizing activity. Symptomatic infection, with symptoms such as loss of taste, dyspnea, rigors, fever and fatigue, was positively associated with anti-RBD IgG positivity by ELISA and Luminex, and with plasma surrogate-neutralizing activity. Our serological assays allow for the prediction of serum neutralization activity without the cost, hazards, time, and expertise needed for surrogate or conventional neutralization assays. Once a cutoff is established, these relatively simple high-throughput antibody assays will provide a fast and cost-effective method of assessing levels of protection from SARS-CoV-2 infection. IMPORTANCE Neutralizing antibody titers are the best correlate of protection against SARS-CoV-2. However, current tests to measure plasma or serum neutralizing activity do not allow high-throughput screening at the population level. Serological tests could be an alternative if they are proved to be good predictors of plasma neutralizing activity. In this study, we analyzed the SARS-CoV-2 serological profiles of two cohorts of health care workers by applying Luminex and ELISA in-house serological assays. Correlations of both serological tests were assessed between them and with a flow cytometry assay to determine plasma surrogate-neutralizing activity. Both assays showed a high positive correlation between IgG levels to S antigens, especially RBD, and the levels of plasma surrogate-neutralizing activity. This result suggests IgG to RBD as a good correlate of plasma surrogate-neutralizing activity and indicates that serology of IgG to RBD could be used to assess levels of protection from SARS-CoV-2 infection.
Normalization of short-chain fatty acid concentration by bacterial count of stool samples improves discrimination between eubiotic and dysbiotic gut microbiota caused by Clostridioides difficile infection-
(Taylor & Francis, 2024-10-12) Sayol Altarriba, Anna; Aira Gómez, Andrea; Villasante, Anna; Albarracín, Rosa; Faneca, Joana; Casals Mercadal, Gregori; Villanueva Cañas, José Luis; Casals Pascual, Climent
Short-chain fatty acids (SCFAs) represent a cornerstone of gut health, serving as critical mediators of immune modulation and overall host homeostasis. Patients with dysbiosis caused by Clostridioides difficile infection (CDI) typically exhibit lower SCFAs levels compared to healthy stool donors and, thus, the concentration of SCFAs has been proposed as a proxy marker of a healthy microbiota. However, there is no consistency in the methods used to quantify SCFAs in stool samples and usually, the results are normalized by the weight of the stool samples, which does not address differences in water and fiber content and ignores bacterial counts in the sample (the main component of stool that contributes to the composition of these metabolites in the sample). Here, we show that normalized SCFAs concentrations by the bacterial count improve discrimination between healthy and dysbiotic samples (patients with CDI), particularly when using acetate and propionate levels. After normalization, butyrate is the metabolite that best discriminates eubiotic and dysbiotic samples according to the area under the receiver operating characteristic (ROC) curve (AUC-ROC = 0.860, [95% CI: 0.786–0.934], p < .0001).
Seven-month kinetics of SARS-CoV-2 antibodies and protective role of pre-existing antibodies to seasonal human coronaviruses on COVID-19
(Nature Publishing Group, 2021-08-06) Ortega, Natalia; Ribes, Marta; Vidal, Marta; Rubio, Rocío; Aguilar, Ruth; Williams, Sarah; Barrios, Diana; Alonso, Selena; Hernández-Luis, Pablo; Mitchell, Robert A.; Jairoce, Chenjerai; Cruz, Angeline; Jiménez, Alfons; Santano, Rebeca; Méndez, Susana; Lamoglia Puig, Montserrat; Rosell, Neus; Llupià García, Anna; Puyol, Laura; Chi, Jordi; Rodrigo-Melero, Natalia; Parras, Daniel; Serra, Pau; Pradenas Saavedra, Edwards; Trinité, Benjamin; Blanco, Julià; Mayor Aparicio, Alfredo Gabriel; Barroso, Sonia; Varela, Pilar; Vilella, Anna; Trilla Garcia, Antonio De Padua; Santamaria, Pere; Carolis, Carlo; Tortajada, Marta; Izquierdo Lázaro, Luis; Angulo Aguado, Ana; Engel, Pablo; Garcia-Basteiro, Alberto L; Moncunill Piñas, Gemma; Dobaño, Carlota, 1969-
Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.
Clinical Variables Related to Functional Capacity and Exertional Desaturation in Patients with COVID-19
(MDPI, 2023-07-20) Larrateguy, Santiago; Vinagre, Julian; Londero, Federico; Dabin, Johana; Ricciardi, Evangelina; Jeanpaul, Santiago; Torres Castro, Rodrigo; Núñez Cortés, Rodrigo; Sánchez Ramírez, Diana; Gimeno Santos, Elena, 1980-; Blanco Vich, Isabel
Impaired functional capacity is one of the most commonly reported consequences among post-COVID-19 patients. This study aimed to analyse the clinical variables related to functional capacity and exertional desaturation in post-COVID-19 patients at the time of hospital discharge. A cross-sectional study was conducted on patients recovering from COVID-19 pneumonia. The main outcomes measures were functional capacity, assessed using the 1 min sit-to-stand test (1 min STST), and exertional desaturation, defined as a drop of ≥4% in the arterial oxygen saturation. Factors used to characterise the participant outcomes included the use of a high-flow nasal cannula (HFNC), prolonged hospitalisation, occurrence of pulmonary embolism during hospitalisation, and underlying comorbidities. A total of 381 participants (mean age = 53.7 ± 13.2 years, 65.6% men) were included. Participants completed a mean of 16.9 ± 6.2 repetitions in the 1 min STST. Exertional desaturation was observed in 51% of the patients. Higher odds of exertional desaturation were found in the participants who used a HFNC (OR = 3.6; 95%CI: 1.6 to 7.8), were admitted in the hospital >10 days (OR = 4.2; 95%CI: 2.6 to 6.8), and had a pulmonary embolism (OR = 3.5; 95%CI: 2.2. to 5.3). Use of a HFNC (β = -3.4; 95%CI: -5.3 to -1.44), a hospital stay >10 days (β = -2.2; 95%CI: -3.4 to -0.9), and a history of pulmonary embolism (β = -1.4; 95%CI: -2.6 to -0.2) were also negatively associated with the 1 min STST. Most post-COVID-19 patients exhibited reduced functional capacity at the time of hospital discharge, and approximately half had exertional desaturation after the 1 min STST. The use of a HFNC, prolonged hospitalisation and pulmonary embolism were the main clinical variables associated with worse a 1 min STST performance and a higher likelihood of exertional desaturation.
Holistic evaluation of the impact of pregnancy urban exposome on infant wheezing and chest infections: an outcome-wide approach
(Elsevier Ltd., 2025-11-08) Gómez Roig, Ma. Dolores; Sunyer, Jordi; Marcon, Alessandro; Johannessen, Ane; Dadvand, Payam; Sinsamala, Robin M.; Anguita-Ruiz, Augusto; Basagaña, Xavier; Foraster, Maria; Gascón, Mireia; Llurba Olivé, Elisa; Luo, Chongliang; Nieuwenhuijsen, Mark J.; Persavento, Cecilia; Rivas, Ioar; Zhao, Yu
Background: Few studies have considered the complex interplay of the urban exposome in association with multiple respiratory outcomes during infancy. Aim: Utilizing an outcome-wide exposome approach, we aimed to assess associations of pregnancy urban exposome with offspring wheezing and chest infections at different time points within the first 18 months of life. Methods: The analysis included data from 1032 mother-child pairs from the Barcelona Life Study Cohort (BiSC) (2018-2021). In total, 44 urban exposome factors were assessed during pregnancy, including air pollution, noise, temperature, humidity, green and blue spaces, and socioeconomic and lifestyle factors. Wheezing and chest infection were evaluated simultaneously at 2, 6, 12, and 18 months. We applied mixed-response sparse reduced-rank regression (MsRRR), with resampling procedures, adjusting for potential confounders. This many-to-many modelling approach identifies exposures concurrently associated with multiple interrelated outcomes. Results: We found 13 exposures consistently associated with wheezing and chest infection across four time-points. Maternal education was the most consistent protective factor with odds ratios (OR) ranging from 0.65 to 0.81 for university and 0.88 to 0.96 for secondary education (vs. primary education) (all p < 0.05). Other important protective factors were size of nearest green space and maternal light-intensity physical activity. NO2 (OR 1.02-1.08), outdoor temperature (OR 1.02-1.04), and noise annoyance (OR 1.01-1.03) were consistently associated with increased risk. Area-level socioeconomic status indicators showed inverse associations. Conclusion: Pregnancy urban exposome may influence both wheezing and chest infections in infancy. Identifying key determinants through an outcome-wide exposome approach can inform targeted public health interventions towards more holistic urban planning strategies.
Agreement and Reliability Between Tele-Assessment and In-Person Assessment of the One-Minute Sit-to-Stand Test in Patients with Chronic Respiratory Diseases
(MDPI, 2025-07-16) Larrateguy, Santiago; Otto Yáñez, Matías; Bogado, Juan; Larrateguy, Luis; Barros Poblete, Marisol; Mazzucco, Guillermo; Blanco Vich, Isabel; Gimeno Santos, Elena, 1980-; Torres Castro, Rodrigo
Background/Objectives: Telemedicine has emerged as a valuable tool for overcoming access barriers in healthcare, particularly in rehabilitation. However, the validity and reliability of remotely conducted physical capacity assessments remain unclear. This study evaluated the agreement and intra-rater reliability between in-person and tele-assessment administration of the one-minute sit-to-stand test (1 min-STST) in individuals with chronic respiratory diseases (CRDs). Methods: In this cross-sectional study, forty adults (55% female; mean age 59.8 ± 15.9 years) diagnosed with CRDs-including chronic obstructive pulmonary disease (52.5%), asthma (20%), and pulmonary fibrosis (20%)-completed the 1 min-STST in two conditions: in person and via tele-assessment. The primary outcome was the number of repetitions completed in each condition. Intra-rater reliability was analyzed using the intraclass correlation coefficient (ICC), and agreement between methods was evaluated with Bland-Altman analysis. Results: The mean number of repetitions was 24.4 ± 8.0 in person and 24.3 ± 8.1 via tele-assessment, with no significant difference (p = 0.78). Excellent reliability was observed (ICC = 0.978, p < 0.001), and Bland-Altman analysis showed good agreement with a mean difference of 0.08 ± 1.7 repetitions and limits of agreement from -3.26 to 3.41. No adverse events were reported. Conclusions: Tele-assessment of the 1 min-STST shows excellent agreement and reliability compared to in-person assessment in individuals with CRDs. These findings support tele-assessment as a valid and practical alternative for evaluating functional capacity remotely. Further research is needed to confirm its implementation in home-based or less-controlled settings.
Effects of pulmonary arterial hypertension therapies on arterial oxygenation in patients with pulmonary hypertension associated with lung disease: a systematic review and meta-analysis
(BMJ Publishing Group, 2025-10-10) Blanco Vich, Isabel; Torres Castro, Rodrigo; Piccari, Lucilla; Roberto Garcia, Agustín; Gimeno Santos, Elena, 1980-; Ramírez, Ana M.; Barberà i Mir, Joan Albert
Background Pulmonary hypertension (PH) associated with lung disease entails a poor prognosis. There is concern about the potential deleterious effect on gas exchange of drugs approved for pulmonary arterial hypertension (PAH) in patients with lung disease. We conducted a systematic review on the effects of drugs approved for PAH on arterial oxygenation in randomised clinical trials (RCTs) conducted in patients with PH associated with lung disease. Methods Five databases were searched until May 2025. We included RCTs with PAH therapies in patients with PH associated with lung disease that reported measurements of arterial oxygenation, either the partial pressure of arterial oxygen (PaO2) or the arterial oxygen saturation (SpO2). For analysis purposes, both measurements were merged into one single variable called ‘overall oxygenation’. As secondary outcomes, we analysed the use of supplemental oxygen and the presence of adverse events related to oxygenation. Results Of the 393 reports returned by the initial search, nine articles, reporting 827 patients (64.6% male), were included. The overall oxygenation at the end of the trial in the intervention group (IG), treated with a PAH therapy, was similar to the control group (standard mean difference (SMD) −0.00; 95% CI −0.17 to 0.18; p=0.98). Similarly, the change in overall oxygenation postintervention in the IG was similar to the control group (SMD 0.01; 95% CI −0.22 to 0.24; p=0.91). Reported adverse events related to oxygenation were similar in the treatment and control arms. Conclusion There is currently no consistent evidence from RCTs to suggest a deleterious effect of PAH therapies on arterial oxygenation in patients with PH associated with lung disease.
Prenatal exposure to synthetic phenols assessed in multiple urine samples and dysregulation of steroid hormone homeostasis in two European cohorts
(National Institute of Environmental Health Science, 2025-05-22) Jedynak, Paulina; Bustamante Pineda, Mariona; Rolland, Matthieu; Mustieles, Vicente; Thomsen, Cathrine; Sakhi, Amrit K.; Sabaredzovic, Azemira; Foraster, Maria; Gascón, Mireia; Gómez Roig, Ma. Dolores; Llurba Olivé, Elisa; Rivas, Ioar; Ouellet-Morin, Isabelle; Bayat, Sam; Lyon-Caen, Sarah; Pozo, Oscar J.; Vrijheid, Martine; Sunyer, Jordi; Slama, Rémy; Dadvand, Payam; Philippat, Claire
Background: Some synthetic phenols alter hormonal pathways involved in successful pregnancy and fetal development. Despite high within-subject temporal variability of phenols, previous studies mostly utilized spot urine samples to assess pregnancy exposure. Herein, we investigated associations between pregnancy exposure to eight phenols assessed in multiple pooled urine samples and steroid hormones assessed in maternal hair reflecting cumulative hormone levels over the previous weeks to months.Methods: We assessed phenol-hormone associations in 928 pregnant women from two pooled cohorts recruited in Spain [Barcelona Life Study Cohort (BiSC), 2018-2021] and France [Assessment of Air Pollution exposure during Pregnancy and Effect on Health (SEPAGES), 2014-2017] using pools of up to 21 samples each, collected in early pregnancy (median gestational age: 18.0 wk), as well as hair collected in late pregnancy (BiSC) or at birth (SEPAGES). We measured two bisphenols, four parabens, benzophenone-3, and triclosan along with metabolites of three adrenal(∑cortisol∑cortisol, ∑cortisone∑cortisone, and 11-dehydrocorticosterone) and two reproductive (progesterone and testosterone) hormones. We ran adjusted linear regressions for each exposure biomarker-outcome pair and Bayesian kernel machine regression for phenols mixture.Results: Bisphenol S was associated with higher cortisol and 11-dehydrocorticosterone concentrations. Propylparaben was associated with lower levels of cortisol, cortisone, and 11-dehydrocorticosterone, while methylparaben was linked to a reduction in cortisol levels. Interestingly, associations identified for parabens were stronger for women carrying female fetuses. No associations for phenol mixture were detected.Conclusions: Our study suggests that pregnancy exposure to bisphenol S and some parabens (propyl- and methylparaben) may affect production of maternal corticosteroid hormones that are important for a successful pregnancy and fetal development.
Functional structure of local connections and differentiation of cerebral cortex areas in the neonate
(Elsevier B.V., 2024-08-08) Falcón Falcón, Carles Maria; Pujol Nuez, Jesús; Blanco Hinojo, Laura; Persavento, Cecilia; Martínez Vilavella, Gerard; Gascón, Mireia; Rivas, Ioar; Vilanova, Marc; Deus Yela, Juan; Gispert, Juan Domingo; Gómez Roig, Ma. Dolores; Llurba Olivé, Elisa; Dadvand, Payam; Sunyer, Jordi
Neuroimaging research on functional connectivity can provide valuable information on the developmental differentiation of the infant cerebral cortex into its functional areas. We examined healthy neonates to comprehensively map brain functional connectivity using a combination of local measures that uniquely capture the rich spatial structure of cerebral cortex functional connections. Optimal functional MRI scans were obtained in 61 neonates. Local functional connectivity maps were based on Iso-Distance Average Correlation (IDAC) measures. Single distance maps and maps combining three distinct IDAC measures were used to assess different levels of cortical area functional differentiation. A set of brain areas showed higher connectivity than the rest of the brain parenchyma in each local distance map. These areas were consistent with those supporting basic aspects of the neonatal repertoire of adaptive behaviors and included the sensorimotor, auditory and visual cortices, the frontal operculum/anterior insula (relevant for sucking, swallowing and the sense of taste), paracentral lobule (processing anal and urethral sphincter activity), default mode network (relevant for self-awareness), and limbicemotional structures such as the anterior cingulate cortex, amygdala and hippocampus. However, the results also indicate that brain areas presumed to be actively developing may not necessarily be mature. In fact, combined distance, second-level maps confirmed that the functional differentiation of the cerebral cortex into functional areas in neonates is far from complete. Our results provide a more comprehensive understanding of the developing brain systems, while also highlighting the substantial developmental journey that the neonatal brain must undergo to reach adulthood.
Prenatal exposure to per- and polyfluoroalkyl substances, fetoplacental hemodynamics, and fetal growth
(Elsevier Ltd., 2024-11-06) Cserbik, Dora; Knox, Bethany; Güil-Oumrait, Nuria; Basagaña, Xavier; Dadvand, Payam; Foraster, Maria; Galmes, Toni; Gascón, Mireia; Gómez Roig, Ma. Dolores; Gómez-Herrera, Laura; Småstuen Haug, Line; Llurba Olivé, Elisa; Márquez, Sandra; Rivas, Ioar; Sunyer, Jordi; Thomsen, Cathrine; Zanini, Maria Julia; Bustamante Pineda, Mariona; Vrijheid, Martine
Introduction: The impact of legacy per- and polyfluoroalkyl substances (PFAS) on fetal growth has been well studied, but assessments of next-generation PFAS and PFAS mixtures are sparse and the potential role of fetoplacental hemodynamics has not been studied. We aimed to evaluate associations between prenatal PFAS exposure and fetal growth and fetoplacental hemodynamics. Methods: We included 747 pregnant women from the BiSC birth cohort (Barcelona, Spain (2018-2021)). Twenty-three PFAS were measured at 32 weeks of pregnancy in maternal plasma, of which 13 were present above detectable levels. Fetal growth was measured by ultrasound, as estimated fetal weight at 32 and 37 weeks of gestation, and weight at birth. Doppler ultrasound measurements for uterine (UtA), umbilical (UmA), and middle cerebral artery (MCA) pulsatility indices (PI), as well as the cerebroplacental ratio (CPR - ratio MCA to UmA), were obtained at 32 weeks to assess fetoplacental hemodynamics. We applied linear mixed effects models to assess the association between singular PFAS and longitudinal fetal growth and PI, and Bayesian Weighted Quantile Sum models to evaluate associations between the PFAS mixture and the aforementioned outcomes, controlled for the relevant covariates. Results: Single PFAS and the mixture tended to be associated with reduced fetal growth and CPR PI, but few associations reached statistical significance. Legacy PFAS PFOS, PFHpA, and PFDoDa were associated with statistically significant decreases in fetal weight z-score of 0.13 (95%CI (-0.22, -0.04), 0.06 (-0.10, 0.01), and 0.05 (-0.10, 0.00), respectively, per doubling of concentration. The PFAS mixture was associated with a non-statistically significant 0.09 decrease in birth weight z-score (95%CI -0.22, 0.04) per quartile increase. Conclusion: This study suggests that legacy PFAS may be associated with reduced fetal growth, but associations for next generation PFAS and for the PFAS mixture were less conclusive. Associations between PFAS and fetoplacental hemodynamics warrant further investigation.
Seroepidemiology of maternal and childhood pathogen exposure in three European mother-child cohorts
(Elsevier BV, 2025-07-21) Karachaliou, Marianna; Vidal, Marta; Pembrey, Lucy; Bustamante Pineda, Mariona; Espinosa, Ana; Mason, Dan; Bañuls Tornero, Marc; Casabonne, Delphine; Roumeliotaki, Theano; Bempi, Vicky; Marín, Natalia; Delgado Saborit, Juana Maria; Rodríguez Loreto, Santa Marina; Ibarluzea, Jesús; Vrijheid, Martine; Aguilar, Ruth; Dobaño, Carlota, 1969-; Kogevinas, Manolis
Objectives: To describe the epidemiology of common pathogens and risk factors among pregnant women and their children. Methods: In three European population-based birth cohorts, we examined 2213 mother-child pairs, contributing 5036 blood samples from pregnancy to 12 years of age. We measured serum immunoglobulin G levels against polyomaviruses (BKPyV, JCPyV, KIPyV, WUPyV, MCPyV), herpesviruses (Epstein-Barr virus [EBV], cytomegalovirus [CMV], varicella-zoster virus), adenovirus 36, Helicobacter pylori , and Toxoplasma gondii with multiplex serology. Results: Among pregnant women, seroprevalence ranged from 18.7% ( H. pylori ) to 95.7% (EBV); among 4-6-year-old children, seroprevalence ranged from 3.6% ( H. pylori ) to 88.4% (BKPyV). Although most primary infections occurred in the first 4 years of life, some children had primary infections at later ages. Seropositive mothers were more likely to have seropositive children, but an intergenerational decrease in seroprevalence was evident for herpesviruses and H. pylori . There were sizeable differences between countries for H. pylori and T. gondii. Non-western ethnicity mothers and their children were more likely to be infected. Female sex (WUPyV, MCPyV, CMV), breastfeeding (CMV), early daycare attendance (CMV, H. pylori ), and obesity (JCPyV, EBV, Adv-36) were associated with child's seroprevalence. Conclusions: European children acquire common pathogens but often experience first exposure beyond early childhood. Differences are expected between and within countries and across generations. (c) 2025 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
The use of saliva and blood progesterone to profile the menstrual cycles of youth professional football players.
(Frontiers Media, 2024-08-21) Ferrer Vidal-Barraquer, Eva; Rodas Font, Gil; Casals Mercadal, Gregori; Trilla García, Antoni; Balagué-Dobón, Laura; González Ruiz, Juan Ramón; Ridley, Katherine; White, Richard; Burden, Richard J.
Background: Understanding individual ovarian hormone cycles and their relationship with health, performance and injuries is highly important to practitioners supporting female athletes. Venous blood sampling is the current gold standard for measuring the ovarian hormones, but the invasive nature of this method presents a major barrier in sport environments. Saliva analysis may offer an alternative method as it is non-invasive, allowing the sample to be collected “in situ”, with relative ease, necessary in applied sport environments. Objective: The aims of this study were: (i) To compare the concentration of progesterone between capillary blood and saliva, (ii) To assess the efficacy of weekly measurements of progesterone for determining if ovulation has occurred in elite eumenorrheic football players, and (iii) To establish a saliva criteria cut-off for establishing ovulation and assessing the sensitivity, specificity and accuracy values of the method. Methodology: Twenty-one professional and semi-professional, Spanish league female football players (18.6 ± 1.5 years, 58.1 ± 6.0 kg, 164.0 ± 4.8 cm) with natural menstrual cycles, completed the study. Capillary blood and saliva samples were collected from each participant on twelve occasions each separated by at least 7 days. All samples were collected in the morning, following an overnight fast. Results: According to luteal phase serum progesterone concentrations, 11 out of 21 (52%) players presented with menstrual irregularities (oligomenorrheic n = 6, anovulatory n = 4, amenorrhoeic n = 1). A significant correlation was observed between plasma and saliva progesterone in the estimated eumenorrheic group (r = 0.80, p = <0.001, 95% CI 0.72–0.86). The association between serum and saliva progesterone was weaker in the oligomenorrheic group (r = 0.47, p = <0.001, 95% CI 0.27–0.64) and was not present in the anovulatory or amenorrhoeic groups. Conclusions: Salivary measurements of progesterone are well correlated with capillary blood when taken during eumenorrheic menstrual cycles and presents a viable, non-invasive method of establishing characteristic progesterone fluctuations in applied sport settings. The strength of the association appears to be concentration dependent. A luteal phase saliva progesterone (P4) >50 pg/ml and >1.5× follicular baseline has good sensitivity, specificity, and accuracy to indicate ovulation compared to established criteria for serum progesterone.
Metabolomic Plasma Profile of Chronic Obstructive Pulmonary Disease Patients
(MDPI, 2025-05-09) Casadevall, Carme; Agranovich, Bella; Enríquez Rodríguez, Cesar Jesse; Faner, Rosa; Pascual-Guardia, Sergi; Castro Acosta, Ady Angélica; Camps Ubach, Ramon; García Aymerich, Judith; Barreiro, Esther; Monsó, Eduard; Seijo Maceiras, Luis Miguel; Soler Cataluña, Juan José; Santos Pérez, Salud; Peces Barba, Germán; López Campos, José Luis; Casanova, Ciro; Agustí García-Navarro, Àlvar; García Cosío, Borja; Abramovich, Ifat; Gea Guiral, Joaquim; EARLY COPD group; BIOMEPOC group
The analysis of blood metabolites may help identify individuals at risk of having COPD and offer insights into its underlying pathophysiology. This study aimed to identify COPD-related metabolic alterations and generate a biological signature potentially useful for screening purposes. Plasma metabolomic profiles from 91 COPD patients and 91 controls were obtained using complementary semi-targeted and untargeted LC-MS approaches. Univariate analysis identified metabolites with significant differences between groups, and enrichment analysis highlighted the most affected metabolic pathways. Multivariate analysis, including ROC curve assessment and machine learning algorithms, was applied to assess the discriminatory capacity of selected metabolites. After adjustment for major potential confounders, 56 metabolites showed significant differences between COPD patients and controls. The enrichment analysis revealed that COPD-associated metabolic alterations primarily involved lipid metabolism (especially fatty acids and acylcarnitines), followed by amino acid pathways and xenobiotics. A panel of 10 metabolites, mostly related to lipid metabolism, demonstrated high discriminatory performance for COPD (ROC-AUC: 0.916; 90.1% sensitivity and 89% specificity). These findings may contribute to improving screening strategies and a better understanding of COPD-related metabolic changes. However, our findings remain exploratory and should be interpreted with caution, needing further validation and mechanistic studies.
YAT2150: Overcoming limitations of traditional amyloid dyes in aggregation studies
(Elsevier Ltd., 2025-03-19) Espargaró Colomé, Alba; Álvarez-Berbel, Irene; Llabrés Prat, Salomé; Domènech Cabrera, Òscar; Busquets i Viñas, Ma. Antonia; Fernàndez Busquets, Xavier; Arce, Elsa M.; Gavín Marín, Rosalina; Río Fernández, José Antonio del; Muñoz-Torrero López-Ibarra, Diego; Luque Garriga, F. Xavier; Sabaté Lagunas, Raimon
Amyloid fibrils, which are aggregates of misfolded proteins characterized by β-sheet-rich structures, are implicated in several neurodegenerative and systemic pathologies, including Alzheimer’s and Parkinson’s diseases and type II diabetes mellitus. Traditional amyloid markers, such as Congo Red and Thioflavin T, are widely used for amyloid detection but present limitations, particularly in cellular assays, due to spectral interference and aggregation inhibition. This study investigates YAT2150, a novel fluorescent dye with enhanced amyloid-binding specificity and sensitivity, as a potential alternative to conventional dyes. We evaluated YAT2150’s efficacy for detecting amyloid aggregates in both in vitro and in cellula assays. First, we compared its fluorescence intensity and binding specificity to that of Thioflavin T in amyloid fibril assays, demonstrating that YAT2150 exhibits high affinity and selectivity for amyloid structures, with minimal interference from non-aggregated proteins. Furthermore, we explored YAT2150’s utility in Escherichia coli as a model system for studying protein aggregation and amyloid formation in a procaryotic cellular context. Our findings indicate that YAT2150 effectively labels amyloid-like inclusion bodies in E. coli, producing a robust fluorescence signal with low background noise. These results suggest that YAT2150 is a promising new tool for amyloid research, offering greater sensitivity compared to traditional dyes, even in complex cellular environments.
Perceptions and future perspectives of medical students on the use of artificial intelligence based chatbots : an exploratory analysis
(Frontiers Media, 2025-01-22) Gualda Gea, Juan José; Barón Miras, Lourdes Estefanía; Bertran, Maria Jesús; Vilella i Morató, Anna; Torà Rocamora, Isabel; Prat, Andrés
Background: Artificial Intelligence (AI) has made a strong entrance into different fields such as healthcare, but currently, medical degree curricula are not adapted to the changes that adopting these types of tools entitles. It is important to understand the future needs of students to provide the most comprehensive education possible. Objective: The aim of this teaching improvement project is to describe the knowledge, attitudes, and perspectives of medical students regarding the application of AI and chatbots with patients, also considering their ethical perceptions. Methods: Descriptive cross-sectional analysis in which the participants were students enrolled in the subject "Preventive Medicine, Public Health and Applied Statistics" during the second semester of the 2023/24 academic year, corresponding to the fifth year of the Degree in Medicine at the University of Barcelona. The students were invited to complete a specific questionnaire anonymously and voluntarily, which they could respond to using their mobile devices by scanning a QR code projected on the classroom screen, we used Microsoft Forms to perform the survey. Results: Out of the 61 students enrolled in the subject, 34 (56%) attended the seminar, of whom 29 (85%) completed the questionnaire correctly. Of those completing the questionnaire, 20 (69%) had never used chatbots for medical information, 19 (66%) expressed a strong interest in the practical applications of AI in medicine, 14 (48%) indicated elevated concern about the ethical aspects, 17 (59%) acknowledged potential biases in these tools, and 17 (59%) expressed at least moderate confidence in chatbot-provided information. Notably, 24 (83%) agreed that acquiring AI-related knowledge will be essential to effectively perform their future professional roles. Conclusion: Surveyed medical students demonstrated limited exposure to AI-based tools and showed a mid-level of awareness about ethical concerns, but they recognized the importance of AI knowledge for their careers, emphasizing the need for AI integration in medical education.
SARS-CoV-2 transmission in teenagers and young adults in Fútbol Club Barcelona's Multidisciplinary Sports Training Academy
(Springer Verlag, 2023-03-14) Hernández García, María; Bassat Orellana, Quique; Fumadó, Victoria; Rodas Font, Gil; Pi, Ramon; Miranda García, Maite; Girona Alarcón, Mònica; Català, Martí; Alonso, Sergio; Alvarez Lacalle, Enrique; López, Daniel; Melé Casas, Maria; Pons Tomàs, Gemma; Fernández de Sevilla Estrach, Mariona; Bonet Carné, Elisenda; Fortuny Guasch, Claudia; Garcia Miquel, Aleix; Jou, Cristina; Adroher, Cristina; Claverol, Joana; Cubells, Marta; Codina, Anna; Cuadras, Daniel; Gratacós Solsona, Eduard; Brotons, Pedro; Muñoz Almagro, Carmen; Prats, Clara; García García, Juan José; Jordán García, Iolanda
Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020-2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 (p < 0.01). A Basketball team showed a significant higher AR. Conclusion: Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential. What is Known: Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum. The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings. What is New: Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied. Routine and semi-professional sports activities seem safe environments to promote during this pandemic.
Long-Term Reassurance with Negative High-Risk Human Papillomavirus (HR-HPV) and Clear Margins After Large Loop Excision of the Transformation Zone (LLETZ)
(MDPI, 2025-02-01) Heydari, Fatima; Sanjosé Llongueras, Silvia de; Peñafiel, Judith; Fernández Montolí, Ma. Eulalia
Background/objective: Women treated with large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia grade 2-3 (CIN2-3) remain at risk of CIN2-3 and cervical cancer for many years. We assessed the roles of high-risk human papillomavirus (HR-HPV) post-LLETZ, surgical margins, and LLETZ characteristics on the long-term risk of CIN2-3. Methods: A retrospective observational study was performed using data for 432 women with a histological diagnosis of CIN2-3 treated by LLETZ between 1996 and 2020 and followed-up until October 2021 at Hospital Bellvitge in Barcelona, Spain. Age, surgical margins, 6-month HR-HPV status, excision type, and cone volume/dimensions were analyzed in association with the risk of persistent/recurrent CIN2-3. The cumulative probability of persistent/recurrent CIN2-3 was calculated using the Kaplan-Meier and Cox models. Results: Persistent/recurrent CIN2-3 was detected in 7.4%, with over 90% found within 5 years post-LLETZ. Predictors of persistent/recurrent CIN2-3 were HR-HPV (HR = 7.36, 95% CI = 3.55-15.26), involved margins (HR = 3.94, 95% CI = 1.68-9.25), uncertain margins (HR = 4.42, 95% CI = 1.55-12.55), and age ≥ 35 years (HR = 2.92, 95% CI = 1.19-7.13). Type 3 excision (p = 0.035) and cone length (p = 0.010) correlated with clear margins. The negative predictive value (NPV) of both negative HR-HPV and clear margins post-LLETZ was 98.7%. Conclusions: The combination of negative HR-HPV and clear margins post-LLETZ provides stronger reassurance against the risk of persistent/recurrent CIN2-3 than do LLETZ characteristics. However, larger excisions in older women likely reduce the risk of involved margins. Close surveillance, including repeat HR-HPV testing in the first 5 years post-LLETZ, is crucial.
Exposure to residential air pollution and the development of functional connectivity of brain networks throughout adolescence
(Elsevier BV, 2025-02-01) Kusters, Michelle S.W.; Granés, Laura; Petricola, Sami; Tiemeier, Henning; Muetzel, Ryan L.; Guxens, Mònica
Background: A few studies linked air pollution to differences in functional connectivity of resting-state brain networks in children, but how air pollution exposure affects the development of brain networks remains poorly understood. Therefore, we studied the association of air pollution exposure from birth to 3 years and one year before the first imaging assessment with the development of functional connectivity across adolescence. Methods: We utilized data from 3,626 children of the Generation R Study (The Netherlands). We estimated residential exposure to PM10, PM2.5, PM 2.5 absorbance, NOX, and NO2 with land-use regression models. Between- and within-network functional connectivity was calculated for 13 cortical networks, and the amygdala, hippo- campus, and caudate nucleus at two assessments (8.6-12.0 and 12.6-17.1 years), resulting in 4,628 scans (2,511 for assessment 1 and 2,117 for assessment 2) from 3,626 individuals. We investigated the association between air pollution and functional connectivity with linear mixed models adjusted for life-style and socioeconomic variables, and corrected for multiple testing. Results: Higher exposure to PM 2.5 from birth to 3 years was associated with persistently lower functional connectivity over time between the amygdala and the ventral attention, somatomotor hand, and auditory networks throughout adolescence (e.g.-0.027 functional connectivity [95 % CI-0.040;-0.013] amygdala - ventral attention network per 5 mu g/m3 higher PM2.5). Higher exposure to PM10 one year before the first imaging assessment was associated with persistently lower functional connectivity between the salience and medial- parietal networks throughout adolescence. Air pollution was not associated with a faster or slower change in functional connectivity with age. Conclusions: Air pollution exposure early in life was associated with persistent alterations in connectivity between the amygdala and cortical networks involved in attention, somatomotor, and auditory function. Concurrent exposure was associated with persistent connectivity alterations between networks related to higher cognitive functions (i.e. the salience and medial-parietal networks).

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