Search Results (19,361)

Background/Objectives: Marine-derived bioactive compounds have attracted increasing interest due to their potential antiviral properties. This study investigated in vitro antiviral activity of oil extracted from the green-lipped mussel (Perna canaliculus, GLM) and low-molecular-weight (LMW) fucoidan from Undaria pinnatifida against three human viruses in mammalian cell systems. herpes simplex virus-1 (HSV-1), respiratory syncytial virus (RSV), and SARS-CoV-2. These marine compounds were selected with the longer-term aim of evaluating their combination as a potential synergistic antiviral strategy. Methods: Antiviral efficacy was assessed using complementary assay platforms, including plaque reduction assays in mammalian cell systems and a lentiviral pseudovirus system delivering a bioluminescent reporter gene in HEK293/ACE2 cells pseudotyped with the SARS-CoV-2 spike glycoprotein. Cytotoxicity was assessed in parallel, and the selectivity index (SI) was calculated as the ratio of CC₅₀ to IC₅₀ for each compound and virus tested. Results: GLM oil showed potential antiviral activity against SARS-CoV-2 pseudovirus (SI > 6.20), with limited activity against RSV (SI > 3.48) and HSV-1 (SI > 2.28). In contrast, LMW fucoidan did not demonstrate antiviral activity against any of the tested viruses. Conclusions: These findings support further investigation of GLM-derived bioactive compounds as potential antiviral agents, including studies to elucidate their mechanisms of action and in vivo studies to confirm their antiviral efficacy. Combination studies were not pursued in the present work as both compounds require further optimisation individually; however, future studies should evaluate their combined antiviral potential, as synergistic or additive effects remain plausible. Full article

Background: In the context of a multi-stakeholder program promoted by Regione Lombardia in collaboration with Fondazione The Bridge and the University of Pavia, the present study investigates the organization and availability of hospital-based vaccination services for high-risk patients. Framing hospitals as strategic hubs for vaccination delivery, the study aimed to map service availability, operational settings and dedicated pathways across the region. Methods: A structured questionnaire was administered in 2025 to 40 healthcare organizations, encompassing 114 hospital facilities, including Local Health and Social Care Authorities (ASSTs) and both public and private Scientific Institutes for Research, Hospitalization and Healthcare (IRCCSs). Descriptive and inferential statistical analyses were performed, and findings were compared with those from the 2023 and 2024 editions of the same survey, developed within the “Vaccination—an opportunity for high-risk patients” project, using Pearson’s chi-square test. Results: In 2025, 99 facilities (86.8% of respondents) reported providing vaccination services for at-risk individuals. Dedicated vaccination pathways were generally available in more than 50% of facilities for nearly two-thirds of the risk categories considered. Vaccination services for diabetic patients were available in 70.7% of facilities. Among healthcare workers, influenza (93%) and SARS-CoV-2 (89.5%) vaccines were the most frequently offered, with rates approximately ten percentage points higher than those of other vaccines. Conclusions: Overall, these findings indicate a regional model progressively consolidating hospital-based vaccination for high-risk groups, with a consistent upward trend in service availability from 2023 to 2025. Full article

Background: Increasing evidence suggests that COVID-19 can induce or exacerbate autoimmune disorders, including immune-mediated thyroid dysfunction. The most common autoimmune thyroid diseases are Graves’ disease and Hashimoto’s thyroiditis; the mechanisms by which viral infections like SARS-CoV-2 trigger these diseases are not fully understood. Objectives: This study aims to systematically review published clinical evidence on the presentation, laboratory characteristics, and outcomes of autoimmune thyroid diseases after COVID-19 infection. Methods: The review followed the PRISMA 2020 framework. Scopus, Web of Science, and PubMed were searched for English-language studies between January 2020 and December 2025 using the terms COVID-19, SARS-CoV-2, autoimmune thyroiditis, Graves’ disease, Hashimoto’s thyroiditis, and autoimmune thyroid disease. Results: In total, 46 studies (five cohort studies and 41 case reports/series) involving 3856 patients were analyzed. The findings indicate that a significant increase in TPOAb prevalence occurs post-COVID-19 infection (15.7% vs. 7.7% in controls). New-onset Graves’ disease (GD) post-COVID-19 presented with higher fT3/fT4 ratios and more aggressive thyrotoxicosis compared to non-viral cases. Rare but severe manifestations included thyrotoxic periodic paralysis, Hashimoto’s encephalopathy, and dilated cardiomyopathy. Conclusions: SARS-CoV-2 may act as a trigger for autoimmune thyroid diseases, particularly in moderate-to-severe infections; however, the strength of this association warrants further investigation with controlled prospective data. Standard therapy remains effective, but thyroid function monitoring is advisable during post-COVID-19 recovery. An interdisciplinary approach is essential for early diagnosis and management of systemic complications. Full article

Background/Objectives: The airway epithelium plays a central role in host defense, inflammatory signaling, and disease progression across infectious, inflammatory, and genetic respiratory disorders. Human nasal epithelial organoids have emerged as accessible and patient-specific in vitro platforms with increasing translational relevance. This systematic review aimed to critically evaluate the current evidence on nasal epithelial organoid models, focusing on donor characteristics, culture methodologies, differentiation strategies, and translational applications. Methods: A systematic search of PubMed/MEDLINE, Embase, Scopus, Ovid MEDLINE, and Cochrane Library was conducted for studies published between 1990 and April 2026. The review followed PRISMA guidelines and was structured according to the PICOTS framework. Eligible studies included in vitro experimental investigations using human-derived nasal epithelial organoids in infectious, inflammatory, or precision medicine contexts. Risk of bias was assessed using the QUIN tool. Results: Seventeen studies met the inclusion criteria. Applications clustered into three principal domains: infectious disease modeling, inflammatory and epithelial remodeling research, and cystic fibrosis precision medicine. Most studies employed expandable three-dimensional Matrigel-embedded organoids or organoid-derived air–liquid interface systems. Infection-focused studies demonstrated variant-specific viral replication dynamics and epithelial immune responses, while inflammatory models reproduced disease-associated differentiation and remodeling phenotypes. Cystic fibrosis oriented studies showed that organoid swelling and electrophysiological assays correlate with CFTR functional rescue and, in selected cases, clinical response. Methodological heterogeneity across protocols and outcome reporting precluded quantitative synthesis. Conclusions: Human nasal epithelial organoids represent versatile translational platforms bridging accessible patient-derived tissue and advanced airway disease modeling. Although variability in culture protocols and functional benchmarks limits standardization, these models hold significant promise for mechanistic investigation, therapeutic stratification, and precision medicine applications. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has greatly impacted public health due to high rates of transmissibility and mutation during the COVID-19 pandemic. Macrodomain 1 (Mac1) of non-structural protein 3 remained well conserved across variants and is critical to suppression of host immune response to infection, making Mac1 a promising target for therapeutic development. Mac1 binds and cleaves the post-translational modification ADP-ribose and is hypothesized to have a downstream effect on the host interferon response, but the exact cellular targets of Mac1 are still unknown. Characterizing the substrates of Mac1 ADP-ribosyl hydrolase activity using a catalytically inactive mutant N40D can reveal critical virus–host interactions to identify protein targets of Mac1 and reveal mechanisms of host interferon suppression. Here, we performed affinity enrichment with WT Mac1 and Mac1 N40D in HEK293T and A549 cells and quantified changes in protein interactions by TMT-multiplexed tandem mass spectrometry. We identified interactions between Mac1 and ADP-ribosylated substrates involved in DNA damage response, cytoskeletal components, and cell cycle regulation. Additionally, several members of the TRiC complex involved in protein folding were selectively enriched with mutant Mac1 from A549 cells. These findings suggest a novel role of Mac1 in regulating host protein folding. Full article

Respiratory infections are among the leading causes of healthcare consultations in paediatric populations. The SARS-CoV-2 pandemic significantly altered both the circulation of respiratory pathogens and the utilisation of healthcare services. This retrospective longitudinal observational study analysed temporal trends in consultations for respiratory infections among children under 15 years of age in the Anoia region between 2017 and 2024. Descriptive analyses and time-series modelling using negative binomial regression were performed. A total of 71,918 consultations were recorded, of which 71.7% occurred in primary care and 28.9% in hospital settings. The mean age of patients was lower in the hospital setting (3.4 years) than in primary care (8.7 years). During the pandemic, consultations decreased by 38% compared with the pre-pandemic period, followed by a rebound in 2022, particularly in hospital care. In the post-pandemic period, hospital consultations remained above pre-pandemic levels, whereas primary care activity tended to stabilise. No increase in bronchiolitis consultations was observed compared with the pre-pandemic period. Full article

Background: Following a significant decline during the 2020–2021 SARS-CoV-2 pandemic, Mycoplasma pneumoniae (MP) experienced a resurgence across Europe in 2023–2024. Although macrolide-resistant MP has increased globally, severe disease can occur even in the absence of resistance, which highlights the importance of rapid molecular characterization for clinical purposes. In this context, clinical severity is often improperly used as a surrogate marker of macrolide resistance, potentially driving unnecessary antibiotic escalation. Methods: We report a severe MP pneumonia occurring during the 2023–2024 resurgence and evaluate macrolide resistance through a rapid two-step workflow (Real Time-PCR screening for A2063G/A2064G followed by confirmatory 23S rRNA sequencing), to assess whether severity predicts resistance and to support antibiotic stewardship. Results: The patient developed acute hypoxic respiratory failure (PaO₂ 54.9 mmHg; P/F ratio 110), extensive centrilobular micronodules on chest CT imaging, significant systemic inflammation and elevated liver enzymes. Respiratory support was escalated from a Venturi mask to a high-flow nasal cannula and BiPAP. MP infection was confirmed by multiplex Real Time-PCR (RT-PCR) and supported by positive IgM/IgG serology. RT-PCR targeting A2063G/A2064G mutations revealed no resistance-associated variants, and Sanger sequencing of an 807 bp 23S rRNA fragment confirmed a wild-type genotype. Despite severe hypoxemic respiratory failure, no resistance-associated variants were detected, documenting a clear severity–genotype mismatch. Clinical and radiological improvement followed second-line antibiotic therapy. Conclusions: Severe MP pneumonia can occur despite the absence of macrolide resistance. During MP re-emergence, clinical severity should not be used to infer macrolide resistance. Integrating nucleic acid amplification test (NAAT) diagnosis with rapid genotyping/confirmatory 23S rRNA sequencing can prevent misclassification, reduce unwarranted broad-spectrum escalation, and strengthen antimicrobial stewardship decisions. Full article

Background: Wastewater-based surveillance (WBS) has emerged as a valuable tool for population-level monitoring of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission, yet the interplay between sampling strategies and disease prevalence in shaping detection performance remains ambiguous. We investigated how grab and composite sampling influence SARS-CoV-2 ribonucleic acid (RNA) detection dynamics and predictive lag times across high- and low-prevalence communities in Selangor, Malaysia. Methods: A 28-week longitudinal study was conducted in Selangor, Malaysia, comparing grab and composite wastewater sampling in communities with high and low Coronavirus disease 2019 (COVID-19) prevalence. SARS-CoV-2 RNA in 348 samples was quantified using digital Reverse Transcription Polymerase Chain Reaction (RT-dPCR), and viral lineages were characterized by Nanopore sequencing. Detection sensitivity and lead times relative to reported cases were evaluated. Results: In low-prevalence settings, grab sampling showed higher detection sensitivity than composite sampling (92.0% vs. 70.0%), whereas both methods achieved similarly high detection in high-prevalence areas (>97.0%). Lag-time analysis indicated that grab sampling in high-prevalence settings was significantly associated with case trends at potential two-week lead (p = 0.024), while composite sampling in low-prevalence settings showed the strongest association at a potential one-week lead (p = 0.0022). Overall, lag structures varied by both sampling strategy and prevalence context. Both sampling approaches captured the replacement of Omicron sublineages (XBB.1.5, XBB.1.9.1, XBB.1.16) and identified additional circulating variants, including EG.5, that were not captured in the available clinical sequencing dataset during the same period. Conclusions: These findings reveal that local transmission intensity is associated with the utility of different sampling designs. Context-specific optimization of WBS sampling strategies enhances sensitivity, reduces detection lag, and strengthens early warning and genomic-tracking capacity in public health surveillance frameworks. 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

COVID-19 remains a challenge to the global healthcare despite the end of the pandemic, including due to the significant involvement of children in the epidemic process. During the pandemic period, an increase in the incidence of Sudden Unexpected Infant Death (SUID) and Sudden Infant Death Syndrome (SIDS) was observed. Currently, their rates remain elevated compared to the prepandemic period. The pathogenetic mechanisms underlying the fulminant course of infection in infants leading to fatal outcomes remain insufficiently understood. In this study, we report for the first time the results of histological and immunohistochemical examination of the lungs in a case of COVID-19-associated SUID in a 2-month-old infant. The absence of similar studies in the available literature limits opportunities for analyzing the pathogenesis of SUID. Our data allow a detailed characterization of the histological changes in the lungs, the localization and range of SARS-CoV-2 nucleocapsid protein expression, the identification of molecular mechanisms underlying apoptosis in the pulmonary microvascular endothelium, and the elucidation of the role of endothelial dysfunction. Particular attention in this article is devoted to the role of cytokines (IL-6, TNF-α, and IFN-γ) in the pathogenesis of hyperacute viral infection. The obtained data demonstrate substantial differences between the observed changes and the classic presentation of COVID-19 in older children. These findings offer prospects for improving prevention strategies and developing targeted therapy for fulminant forms of COVID-19, while also contributing to the understanding of SIDS pathogenesis. Full article

Background/Objectives: In 2020, the world found itself in the midst of the SARS-CoV-2 pandemic. The virus has spread globally, resulting in over 779 million cases worldwide. In response to this crisis, there arose a critical need for diagnostic techniques capable of meeting the overwhelming global demand, including RT-qPCR as the gold standard due to its high sensitivity and specificity. However, RT-qPCR has its limitations, including susceptibility to factors such as inadequate sample collection, variations in viral load, and insufficient clinical validation, all of which can lead to false negatives. Consequently, this study aims to evaluate the clinical performance of four commercial RT-qPCR kits for detecting SARS-CoV-2. Methods: The study utilized 200 nasopharyngeal swab samples collected in January 2022, comparing kits from Qiagen, Seegene, Bio-Manguinhos, and IBMP. Results: Results indicated significant differences in kit performance, with 66% of samples showing consistent results across all kits, and 34% showing discrepancies. Ct values were also analyzed, and statistical tests highlighted varying sensitivities among the kits, ranging from 100% to 86.82%. Conclusions: The study underscores how extraction and purification processes, kit quality, and target gene adequacy critically influence kit performance, influencing the occurrence of false positives and negatives. Full article

Background/Objectives: The COVID-19 pandemic has raised concerns about maternal mental health, particularly among women infected during pregnancy. This study aimed to examine longitudinal changes in depressive and anxiety symptoms and subjective distress among pregnant women in Slovakia with confirmed SARS-CoV-2 infection and to explore the role of obstetric complications and vaccination status in these trajectories. Methods: In this retrospective longitudinal study, women with SARS-CoV-2 infection during pregnancy were assessed at three time points: during infection, six weeks postpartum, and one year postpartum (11 March 2020–5 May 2023). Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS; cut-off ≥ 11), anxiety symptoms were measured using the EPDS-3A subscale (cut-off ≥ 5), and subjective distress was measured using visual analogue scales (VAS). A repeated-measures ANCOVA design was used to evaluate within-subject changes over time while adjusting for vaccination status and pregnancy complications. Results: Of 1184 contacted women, 170 provided complete data. The proportion of women exceeding the EPDS cut-off decreased from 27.6% during infection to 17.6% at six weeks postpartum and 4.7% at one year postpartum. Anxiety symptoms showed a similar pattern, declining from 27.6% during infection to 20.6% at six weeks postpartum and 7.6% at one year postpartum. Repeated-measures analyses confirmed significant time effects across psychological outcomes, with symptom levels decreasing over the postpartum year. Post-infection obstetric complications were associated with higher subjective distress at selected time points. Conclusions: Psychological symptoms were highest during the acute infection period and declined significantly over time. These findings support the importance of timely mental health screening during pregnancy affected by COVID-19, while suggesting that, in many women, psychological distress may decrease across the postpartum year. 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

Mucosal immunity, including antibodies like immunoglobulin A (IgA), function as the body’s first line of defense in the respiratory tract, particularly against viruses. An anti-rS protein IgA enzyme-linked immunosorbent assay (ELISA) was developed using the Omicron XBB.1.5 subvariant of SARS-CoV-2 and was validated to demonstrate the suitability of the method for testing saliva from SARS-CoV-2 vaccine clinical trials. This assay successfully met acceptance criteria for inter-/intra-assay precision, specificity, selectivity, linearity, lower/upper limits of quantitation, and assay robustness. The IgA in saliva was stable for up to 7 freeze/thaw cycles, for up to 48 h at 24 °C, up to 7 days at 4 °C, up to 3 weeks at −20 °C, and up to 1 year at −80 °C. After validation using Omicron XBB.1.5 rS protein, cross-reactivity was demonstrated with the SARS-CoV-2 variant JN.1. This validated IgA assay can be a valuable tool to assess mucosal IgA levels in SARS-CoV-2 clinical trials. Full article

This study examined alterations in serum redox biomarkers before and one month after administration of the coronavirus disease 2019 (COVID-19) booster (third) doses across four vaccine regimens. A longitudinal cohort of 410 adults was analyzed following homologous Pfizer-BioNTech, Sinopharm [Vero Cell]-Inactivated, Sputnik V, or heterologous Sinopharm/Pfizer vaccination. Serum total proteins, albumin, total thiols, nitrites, ferric-reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity were measured, with DPPH interpreted as an ex vivo surrogate of serum radical-scavenging capacity. Additional analyses included stratification by prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, multivariable regression, correlation analysis, effect-size estimation, and sensitivity testing. Booster vaccination was associated with modest but consistent decreases in DPPH activity, albumin, and total proteins, whereas FRAP, nitrite, and total thiol levels remained stable. This pattern supports a transient shift in antioxidant buffering capacity but, by itself, does not exclude oxidative stress, as direct oxidative damage markers were not assessed. The most pronounced changes were observed in Sinopharm-based regimens, particularly in the heterologous Sinopharm/Pfizer group. Prior SARS-CoV-2 infection did not materially alter the qualitative response pattern, whereas older age and comorbidities were associated with greater declines in DPPH activity and albumin. Overall, the findings indicate a modest, transient redox-associated response following booster-induced immune activation and suggest that host-related factors, such as age and comorbidity burden, may accentuate short-term changes in antioxidant buffering capacity. Full article