Search Results (5,253)

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 syndrome (LC) show substantial clinical overlap, but direct comparative microbiome studies remain limited. Methods: In this cross-sectional study, we compared the fecal gut microbiome of patients with ME/CFS, LC, and healthy controls (HC) within a unified analytical framework using 16S rRNA profiling, differential abundance testing, and multivariate modeling. We also examined associations between microbiome variation and questionnaire-derived symptom-domain scores. Results: Alpha-diversity did not differ significantly among groups, whereas beta-diversity analyses showed small but significant disease-associated community differences with broad overlap between cohorts. Differential abundance analysis identified stronger signals in disease-versus-control contrasts than in the direct ME/CFS vs. LC contrast. Both ME/CFS and LC shared enrichment of Sutterella and depletion of Terrisporobacter and Lachnospiraceae relative to HC. Predicted functional profiling showed shared disease-versus-control changes in pathways related to anaerobic acetate/H₂ carbon flow, inositol/polyol degradation, phosphonate/C1-related metabolism, and lysine-derived fermentation. Regression analyses showed the strongest microbiome associations with fatigue-related and physiosomatic domains, while affective, cognitive, and gastrointestinal outcomes showed weaker signals. Conclusions: Overall, these findings support the presence of overlapping but non-identical gut microbiome alterations in ME/CFS and LC. The results provide a basis for future longitudinal and multi-omics studies aimed at clarifying the stability, functional relevance, and clinical utility of these microbial patterns. Full article

Objectives: This study aimed to estimate the prevalence of Post-COVID-19 Syndrome among older adults in Indonesia, using time-based definitions of symptoms persisting beyond >4 weeks, >8 weeks, and >12 weeks. Methods: A retrospective cohort study was conducted among 329 older patients (≥60 years) hospitalized with COVID-19 in two tertiary hospitals in Jakarta from January to December 2021. Data on risk factors and persistent symptoms were collected from medical records and interviews. Results: The prevalence of Post-COVID-19 Syndrome was 31% (>4 weeks), 18.24% (>8 weeks), and 10.64% (>12 weeks). Significant predictors included frailty (OR 2.814), immobility during hospitalization (OR up to 4.767), higher number of initial symptoms (OR 2.043), constipation, instability, and sensory impairment during follow-up. Conclusions: Frailty, symptom burden, and geriatric syndromes, particularly immobility are strongly associated with Post-COVID-19 Syndrome in older adults. Clinical Implications: Early identification of frailty, geriatric syndromes (especially immobility), and high initial symptom burden is essential for risk stratification, targeted monitoring, and implementation of preventive and rehabilitative interventions to reduce long-term post-COVID-19 complications in older populations. Full article

COVID-19 has had profound global impacts, and Long COVID may continue to affect quality of life and well-being in some individuals. Young adults may be particularly vulnerable to these impacts due to ongoing physiological, behavioral, and psychological development. This study aimed to examine the associations between Long COVID, mental health-related outcomes, and quality of life among university students. A total of 365 Thai undergraduate students participated in this cross-sectional study screening for Long COVID. Long COVID symptoms, mental health, sleep quality, and quality of life were assessed using validated Thai versions of the Long COVID Screening Questionnaire, DASS-21, PSQI, and EQ-5D-5L. Regression and group comparison analyses were conducted between participants with Long COVID and those without Long COVID. Fatigue and cough were the most reported symptoms, while sleep disturbances were also prevalent. Long COVID was associated with significantly lower quality of life scores (p = 0.035). However, no significant differences were observed in DASS-21 or PSQI scores between groups. Vaccination doses and prior COVID-19 infections differed significantly between groups (p < 0.001 and p = 0.017). These findings highlight the multisystem impacts of Long COVID and emphasize the importance of identification and supportive interventions to enhance student health and well-being. Full article

Background: Globally, around 400 million people are estimated to be affected by long COVID, yet treatment options remain scarce. A systematic review published in 2025 indicated that non-invasive brain stimulation may help reduce some long COVID symptoms. If repetitive transcranial magnetic stimulation (rTMS) has therapeutic potential for these patients, then a clear synthesis of the evidence is necessary to determine efficacy and potential for implementation. Methodology: This systematic review and narrative synthesis was conducted in accordance with PRISMA guidelines. The search, completed on the 4th of December 2025, covered four databases and grey literature. Studies were included if they examined long COVID and rTMS. Findings: A meta-analysis was not possible due to insufficient reported data across studies. Instead, a structured narrative synthesis was conducted on four included studies. The structured narrative synthesis of four studies indicates that rTMS is feasible and is associated with reported improvements in fatigue, mood, and cognitive symptoms in individuals with long COVID. However, all included evidence is based on uncontrolled case series and retrospective analyses, meaning no causal conclusions can be drawn and findings should be interpreted as exploratory. Conclusions: Taken together, the evidence remains preliminary and highlights the need for well-designed randomised controlled trials to assess efficacy. Full article

Background/Objectives: Post-COVID syndrome (PCS) is frequently associated with persistent cognitive complaints such as fatigue and impaired concentration, yet objective markers related to cognitive dysfunction are lacking. Pupillary oscillation metrics have emerged as non-invasive indicators of task-related cognitive load and autonomic regulation. This study investigated the Index of Pupillary Activity (IPA) and the Low/High Index of Pupillary Activity (LHIPA) in a large cohort of patients with PCS compared with healthy controls. Methods: In this cross-sectional study, 526 participants (397 PCS patients, 129 controls) performed a standardized virtual reality-based stereoscopic task at three disparity levels: 275 arcsec (high difficulty), 550 arcsec (medium difficulty), and 1100 arcsec (low difficulty), using a head-mounted display with integrated eye tracking. Continuous pupillometry data were recorded, and IPA and LHIPA were calculated. Linear mixed-effects models with random intercepts for participants were applied, adjusting for age, sex, and task difficulty. Results: Both IPA and LHIPA were significantly lower in PCS patients than in controls at all three task difficulty levels in post hoc model-based contrasts. In adjusted mixed-effects models, PCS was also associated with lower overall IPA ($\beta =-0.111$, 95% CI $-0.160$ to $-0.062$, $p<0.001$) and lower overall LHIPA ($\beta =-0.164$, 95% CI $-0.253$ to $-0.074$, $p<0.001$). Lower task difficulty was associated with higher values of both metrics: for IPA, $\beta =0.164$ at 550 arcsec and $\beta =0.287$ at 1100 arcsec (both $p<0.001$); for LHIPA, $\beta =0.161$ at 550 arcsec and $\beta =0.254$ at 1100 arcsec (both $p<0.001$), relative to 275 arcsec. Thus, both indices showed an inverse association with task difficulty. Age was negatively associated with both metrics, whereas male sex was positively associated with both. No significant interaction between cohort and task difficulty was observed. Conclusions: PCS was associated with reduced IPA and LHIPA during a standardized stereoscopic task. These findings indicate altered task-related pupillary dynamics in PCS and may reflect altered cognitive-load processing and autonomic regulation. LHIPA, and with caution also IPA, may contribute to the objective assessment of task-related pupillary alterations in PCS. Full article

Background: The relationship between allergic status, SARS-CoV-2 infection, Long COVID, and post-restriction respiratory outcomes in children remains incompletely understood. This study aimed to explore the associations between allergic status and Long COVID, as well as between SARS-CoV-2 vaccination and post-restriction changes in allergic rhinitis (AR), asthma, and upper respiratory infections, in a pediatric tertiary-care cohort. Methods: We conducted a single-center, questionnaire-based observational study involving children aged 0–16 years, who were followed at the Pediatric Allergy Clinic of Umberto I Hospital in Rome. Parents completed an email-based questionnaire addressing SARS-CoV-2 infection, vaccination, persistent post-infectious symptoms, allergic diseases, and respiratory infections following restrictions. Analyses of Long COVID were limited to children with confirmed SARS-CoV-2 infection. Results: A total of 214 questionnaires were analyzed. Allergic status was not significantly associated with SARS-CoV-2 infection in the overall cohort. Among infected children, allergic status was independently associated with higher odds of Long COVID (adjusted OR 3.12, 95% CI 1.20–8.09; p = 0.019). Severe acute infection was also strongly associated with Long COVID (adjusted OR 6.84, 95% CI 2.72–17.21; p < 0.001). Complete vaccination was associated with lower odds of SARS-CoV-2 infection in the overall sample (adjusted OR 0.20, 95% CI 0.09–0.46; p < 0.001) but was not independently associated with Long COVID among infected children. After the removal of COVID-19 restrictions, 90.1% of allergic children reported worsening AR and 52.0% reported worsening asthma, with no significant association with SARS-CoV-2 infection or Long COVID. Group A Streptocossus (GAS) pharyngitis was reported in 50.0% and viral pharyngitis in 10.7% of the cohort, with no significant differences between allergic and non-allergic children. Conclusions: In this single-center, questionnaire-based pediatric cohort, allergic status was correlated with increased likelihood of Long COVID among children with confirmed SARS-CoV-2 infection; however, it was not associated with a higher risk of infection itself. Complete vaccination was linked to a reduced risk of infection, whereas no independent correlation with Long COVID was identified. Post-restriction exacerbation of allergic respiratory symptoms was prevalent, while the incidence of bacterial and viral pharyngitis did not vary significantly according to allergic status. Full article

Background: The COVID-19 pandemic has generated widespread concerns regarding its long-term effects on children’s mental health. While numerous studies documented increased psychological distress among children during the pandemic, less is known about how children’s emotional and behavioral functioning have evolved in the post-pandemic period. Objective: This study examines patterns of children’s mental health using survey data collected in 2023 and 2025. Guided by the dual-factor model of mental health, the analysis considers both psychological difficulties and positive social functioning in order to provide a multidimensional understanding of children’s well-being. Method: Data were collected using the Strengths and Difficulties Questionnaire (SDQ-25), a widely used behavioral screening instrument assessing emotional symptoms, conduct problems, hyperactivity/inattention, peer relationship problems, and prosocial behavior. These domains were analyzed across two time points to explore patterns of change in internalizing difficulties, externalizing difficulties, and social strengths among school-age children in the post-pandemic context (N = 1262 students in 2023 and N = 575 students in 2025). Results: The findings suggest that children’s mental health after the pandemic reflects both persistent vulnerability and adaptive capacity. Emotional symptoms and behavioral challenges remain present among a proportion of children, indicating that the psychological effects of pandemic-related disruptions may extend beyond the immediate crisis period. At the same time, many children demonstrate relatively stable levels of prosocial behavior, highlighting the continued importance of positive social functioning as a protective factor for psychological adjustment. Contributions: These results underscore the importance of adopting a comprehensive perspective on children’s mental health that recognizes both difficulties and strengths. The study highlights the role of schools and families in supporting children’s post-pandemic recovery through early mental health screening, social–emotional learning initiatives, and programs that promote empathy and peer support. Such approaches may contribute to strengthening children’s resilience and long-term well-being in the aftermath of large-scale social disruptions. Full article

Individuals with cystic fibrosis (CF) face significant treatment burdens, and as life expectancy has increased, there is growing emphasis on their psychosocial well-being. Prevalence data indicate that approximately one-quarter to one-third of individuals with CF and their caregivers experience clinically significant anxiety or depression. Specifically, pooled global estimates report an anxiety prevalence of 24.9% (95% CI: 20.8–28.9%) and depression prevalence of 13–33% in adults with CF, with caregivers experiencing even higher rates (anxiety: 35–38%; depression: 20–35%). Depression is independently associated with a nearly twofold increase in mortality risk and substantially higher healthcare costs, underscoring its prognostic significance. These mental health comorbidities are consistently associated with reduced treatment adherence, diminished quality of life, increased healthcare utilisation, and decreased survival. Accordingly, psychological well-being has emerged as a key patient outcome that directly shapes engagement with care and the effectiveness of long-term CF management. International CF guidelines now recommend routine mental health screening within multidisciplinary care frameworks. Evidence-based interventions include cognitive–behavioural therapy (CBT), which is endorsed as a primary treatment, although access remains limited, and stepped-care pharmacotherapy, primarily selective serotonin reuptake inhibitors (SSRIs), for moderate to severe symptoms. Telemedicine and other digital health approaches have expanded access to psychological support, with remote CBT and online programmes demonstrating feasibility and symptom improvement during the COVID-19 pandemic and beyond. The advent of CFTR modulator therapies has significantly altered clinical outcomes, enabling many patients to achieve improved lung function and daily functioning. Nevertheless, mental health challenges persist, as individuals navigate new identity shifts and anxieties despite enhanced physical health. The implementation of mental healthcare remains inconsistent; while screening rates have increased, timely follow-up and integrated psychosocial support are frequently insufficient across care centres. This narrative review highlights the ongoing need to integrate mental health management into CF care to optimise adherence, patient outcomes, and long-term survival in the current therapeutic landscape. Full article

Background: Hypertension is one of the most prevalent comorbidities in patients with COVID-19 and a major contributor to chronic kidney disease (CKD). Traditional kidney injury markers, including creatinine, estimated glomerular filtration rate (eGFR) and microalbuminuria, reflect renal injury only after substantial nephron loss has already occurred. Urinary podocyte proteins, such as nephrin (nephrinuria), have been suggested as early markers of glomerular barrier dysfunction; however, their clinical behavior and diagnostic value in hypertensive patients with previous SARS-CoV-2 infection are unknown. Aim: To assess urinary nephrinuria, microalbuminuria, transforming growth factor β1 (TGF-β1), aldosterone, vascular endothelial growth factor A (VEGF-A) and renal hemodynamics across different stages of hypertension in patients with and without a history of COVID-19 and to assess the response to conventional antihypertensive and nephroprotective treatment. Methods: In a prospective comparative cohort study, 120 patients (aged 30–60 years) with stage I–III essential hypertension were stratified by COVID-19 history into a post-COVID-19 group (n = 60) and a non-COVID-19 group (n = 60); within each group, 20 patients were assigned to each hypertension stage. Comparisons were performed between the post-COVID-19 and non-COVID-19 subgroups at the same hypertension stage. Serum creatinine, cystatin-C, aldosterone, TGF-β1 and VEGF-A, urinary microalbumin and nephrin and intrarenal Doppler hemodynamics were measured at baseline and after six months of guideline-based treatment. Results: Nephrinuria was markedly increased in post-COVID-19 patients in all stages of hypertension, including stage I, where serum creatinine, cystatin-C and eGFR were within the normal range (126.5 ± 9.1 vs. 91.9 ± 8.3 pg/mL, p < 0.01). Nephrinuria was strongly correlated with renal functional reserve (r = −0.824, p < 0.001), eGFR (r = −0.797, p < 0.001), microalbuminuria (r = 0.758, p < 0.001), aldosterone (r = 0.613, p < 0.001) and VEGF-A (r = 0.589, p < 0.001). Antihypertensive and nephroprotective treatment for six months decreased nephrinuria, blood pressure and TGF-β1, with more limited effects in stage III disease. Conclusions: Nephrinuria was found to be an early marker of renal involvement in COVID-19, occurring before microalbuminuria and conventional functional markers and with a greater relative difference than these markers in stage I disease, suggesting podocyte injury as an early and potentially reversible mechanism of post-COVID renal involvement in hypertensive patients. Nephrinuria seems to be a potential biomarker for early renal surveillance in this population and its prognostic role for incident CKD needs to be validated in longitudinal outcome studies. Full article

Achieving sustainable development requires decoupling economic growth from environmental degradation. In this context, this study examines the effects of tourism arrivals on CO₂ intensity and energy intensity, two key indicators of environmental sustainability aligned with SDGs 7 and 13. Panel autoregressive distributed lag (ARDL) and nonlinear ARDL models are employed using a balanced panel of 54 countries over the period 1996–2023. In addition, Wald tests for long-run asymmetry, dynamic multiplier analysis, and Dumitrescu–Hurlin causality tests are applied. The results confirm the existence of stable long-run relationships between tourism arrivals and both CO₂ intensity and energy intensity. In the symmetric framework, tourism growth is associated with significant long-run reductions in CO₂ and energy intensity, while short-run effects are negative and significant only for CO₂ intensity. In the asymmetric framework, positive tourism shocks generate stronger and more persistent reductions in both intensity measures, whereas negative shocks lead to weaker environmental efficiency gains. Moreover, the Wald test shows the existence of long-run asymmetry between positive and negative tourism shocks. In addition, the dynamic multiplier analysis confirms that environmental intensity adjusts gradually over time following tourism shocks. Finally, Dumitrescu–Hurlin causality tests indicate bidirectional Granger causality relationships between tourism arrivals and environmental intensity indicators. The findings are robust to dynamic endogeneity, the COVID-19 shock, and country heterogeneity. Overall, the findings indicate that tourism arrivals contribute to lowering long-term environmental intensity, consistent with relative decoupling and the goals of sustainable tourism development. Full article

Excitotoxicity is one of the factors that participates in neurodegeneration, impairing neuronal and glial cells’ function, and leading to the development of chronic neurodegenerative diseases. The main mechanism of action lies in the overstimulation of excitatory receptors, especially the NMDA (N-methyl-D-aspartic acid) receptor, by glutamate, which promotes a massive influx of Ca²⁺ that is not sufficiently buffered by the intracellular machinery, or not released by mechanisms such as Ca²⁺ ATPase and plasma membrane Ca²⁺/Na⁺ exchanger promoting, among other toxic effects, mitochondrial damage and an increase in reactive oxygen species (ROS). Notably, many cases reported of long COVID-19 describe significant brain alterations and neuropsychiatric disorders, including delirium, depression, etc., and patients required increased use of antidepressant or anxiolytic drugs, for example. In addition, emerging evidence links neurodegeneration as a potential long-term sequelae associated with an increased number of patients with cognitive disorders. This review analyzes data from the literature regarding brain alterations associated with post-COVID-19 syndrome and explores a potential link to the excitotoxicity pathways, due to its participation in neurodegeneration by homeostatic failure, and it is clearly present in various brain conditions, such as Alzheimer’s and Parkinson’s diseases. Full article

A three-year (January 2020–December 2022) daily dataset of 16 polycyclic aromatic hydrocarbons (PAHs) collected in parallel with PM_2.5 and a suite of meteorological variables at a coastal Mediterranean urban site in southern Italy (Pomigliano d’Arco, Campania) is presented and analysed. Raw PAH time series were decomposed into a long-term trend component (LT), a seasonal component (ST), and a residual component (RT) using an iterative missing-value-robust Kolmogorov–Zurbenko (KZ) moving-average filter. Spearman rank correlations between PAH concentrations and four meteorological predictors (mean temperature, relative humidity, mean wind speed, and maximum wind speed) were computed for each congener. Diagnostic molecular ratios—Fla/(Fla + Pyr), BaP/BghiP, Indeno[1,2,3-cd]pyrene/(IcdP + BghiP), and BaA/(BaA + Chr)—were evaluated seasonally and interpreted jointly with an information-theoretic Bayesian mixture modelling procedure (SNOB/MML) and with the documented susceptibility of some PAH ratios, especially BaP-containing ratios, to atmospheric ageing, phase repartitioning and summer photodegradation. Total PAH concentrations (sum of 16 congeners) ranged from <1 ng m⁻³ in summer to 46 ng m⁻³ during winter high-pollution episodes, with BaP peaking at ≈6.7 ng m⁻³. Because BaP was measured in the PM_2.5 fraction, comparisons with the EU annual target value of 1 ng m⁻³ established for PM₁₀-bound BaP are treated as indicative context only, not as formal compliance statements. Pronounced seasonal variability was driven primarily by residential heating emissions, and the incremental lifetime cancer risk (ILCR) for inhalation exposure reached $1.03\times {10}^{-4}$ (95% CI: $0.88$–$1.20\times {10}^{-4}$) during the heating season under a continuous outdoor-exposure worst-case scenario. The absolute ILCR magnitude is conditional on the selected TEF scheme and on the adopted BaP unit-risk coefficient; under an additional indoor-dominated scenario (16 h day⁻¹, infiltration factor 0.6), the corresponding risk remained above the conventional ${10}^{-6}$ benchmark. An anomalous near-background PAH signal during spring 2020 is attributed to the COVID-19 national lockdown, which reduced total PAH concentrations by approximately 85% relative to the seasonal component predicted by the iterative moving-average filter for the same calendar window. Source apportionment via diagnostic ratios identifies residential/biomass combustion as the dominant cold-season source and vehicular emissions as the prevailing warm-season source. These results provide a novel characterisation of PAH pollution dynamics in the undersampled southern Mediterranean and provide evidence to support targeted abatement policies. Full article

Bringing a new drug to market is a complex, costly, and lengthy process, averaging $2.6 billion and about ten years of research and development. It involves multiple stages, from target discovery to post-approval monitoring, and relies heavily on innovation driven by collaboration among pharmaceutical sciences, biology, biochemistry, engineering, and artificial intelligence. Drug discovery can be divided into four main stages: target selection and validation; compound screening and optimization; preclinical studies; and clinical trials. First, researchers identify and validate a biological target associated with a disease using genomic, proteomic, and bioinformatic approaches. Next, potential compounds (“hits”) are identified through methods such as high-throughput and virtual screening, followed by iterative chemical optimization and functional testing. Promising candidates undergo preclinical in vivo studies to assess pharmacokinetics, pharmacodynamics, and toxicity. Clinical development proceeds in three phases: Phase I evaluates safety in healthy volunteers; Phase II assesses efficacy in patients; and Phase III confirms efficacy and safety in larger populations. After successful trials, regulatory agencies review the data for approval. While small molecules have long dominated due to their stability and oral bioavailability, biologics—such as monoclonal antibodies and mRNA-based therapies—have grown rapidly, highlighted by COVID-19 vaccine development and increasing FDA approvals. Full article

Why do pandemics keep emerging despite decades of surveillance and response? Paleopathology, the study of disease traces in ancient remains, has been revolutionized by ancient DNA (aDNA) analysis and next-generation sequencing (NGS). Reconstructing pathogen genomes from archaeological material enables the identification of extinct lineages, the refinement of disease chronologies, and the characterization of long-term host-pathogen co-evolution. This provides context for public health challenges, including the emergence of pandemics and antimicrobial resistance (AMR). Infectious diseases are increasingly understood as complex phenomena arising from biological, ecological, and sociopolitical forces. Integrating paleopathology, aDNA, and paleomicrobiology supports a deep-time syndemic framework, revealing how recurring biosocial drivers have structured infectious disease risk throughout history. Ancient resistome studies demonstrate that AMR predates modern antibiotic use, reframing resistance as an intrinsic ecological feature rather than solely a modern phenomenon. Coronavirus disease 2019 (COVID-19) reaffirmed how infection intersects with chronic disease, health system fragility, and social inequities. This review highlights how integrating evolutionary perspectives into One Health shifts surveillance from a reactive approach to upstream risk mitigation and spillover prevention. Full article

Introduction: The COVID-19 pandemic disrupted immunization services in Togo, resulting in 69,672 “zero-dose” and 24,846 “under-vaccinated” children by the end of 2023. This study assessed the effectiveness, acceptability, and feasibility of a social marketing approach deployed during the 2025 Big Catch-Up initiative in Togo. Methods: A convergent mixed-methods study was conducted in 17 priority health districts. The quantitative component compared vaccination coverage before and after the intervention using administrative data. Chi-squared test for linear trend compared district-level coverages, and statistical significance was set at p < 0.05 for all tests. The qualitative component used in-depth interviews with key informants to collect data, followed by thematic content analysis. The intervention was grounded on the social marketing framework with 4 pillars (4Ps): Product, Price, Place, and Promotion. Results: Coverage increased dramatically: Penta1 from 1% to 64%, Penta3 from 1% to 45%, MR1 from 4% to 50%, and MR2 from 6% to 49% (all p < 0.001). Togo ranked 3rd out of 24 African countries for Penta1 progress. The approach demonstrated high community acceptability, with Vaccination Monitoring Committees praised as being culturally appropriate. Key concerns included sustainability and resource constraints. Conclusions: Social marketing was associated with increased community adherence and immunization coverage improvement. However, long-term sustainability requires the institutionalization of community structures with domestic funding and continued health system strengthening. Full article