Search Results (19,235)

Background: People living with HIV (PLWH) constitute a vulnerable population during the COVID-19 pandemic; however, it remains uncertain whether long-term suppressive antiretroviral therapy (ART) restores sufficient immune competence to support robust hybrid immunity. While vaccination followed by breakthrough infection—termed hybrid immunity—typically elicits potent humoral responses in immunocompetent individuals, the functional quality and breadth of these responses against evolving Omicron subvariants remain poorly characterized in PLWH. This study aimed to assess functional antibody responses, including neutralizing activity and Fc effector functions, in vaccinated and unvaccinated PLWH who experienced breakthrough infection with Omicron subvariants BA.4/5 or BF.7. Methods: We enrolled three cohorts between December 5 and December 20, 2022: 25 HIV-negative individuals with breakthrough infection (BTI-HC), 20 ART-experienced PLWH with breakthrough infection following three-dose COVID-19 vaccination (BTI-HIV), and 10 ART-experienced PLWH with primary infection without prior vaccination (PI-HIV). All HIV-positive participants were receiving suppressive ART with regimens based on non-nucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitors for a median of 3.4 years. We measured receptor-binding domain (RBD)-specific IgG, neutralizing antibody titers against ancestral D614G, Delta, BA.1, BA.4/5, BF.7, XDV, KP.2, and KP.3 variants, and antibody-dependent cellular cytotoxicity (ADCC) responses. Results: Despite lower absolute CD4⁺ T cell counts, BTI-HIV participants mounted RBD-binding IgG, neutralizing antibody, and ADCC responses that were comparable to BTI-HC and significantly exceeded PI-HIV across all tested variants. Both breakthrough infection cohorts exhibited immunological imprinting, with higher neutralizing titers against ancestral D614G than infecting BA.4/5 or BF.7 variants. Emerging variants XDV, KP.2, and KP.3 demonstrated substantial neutralization escape in all groups. PI-HIV showed markedly diminished neutralization breadth and failed to generate enough responses against all tested Omicron strains. Conclusions: Suppressive ART enables PLWH to mount hybrid immunity—conferred by vaccination followed by BF.7 or BA.4/5 breakthrough infection—with neutralizing and ADCC responses comparable to HIV-negative individuals, and significantly exceeding those of unvaccinated PLWH with primary infection. This underscores the critical role of vaccination in establishing effective hybrid immunity in this population. However, we observed immunological imprinting, with higher titers against ancestral strains than against infecting variants, and substantial escape by emerging sublineages XDV, KP.2, and KP.3 across all groups. These findings support prioritizing updated variant-containing vaccines for HIV-positive populations and reinforce the essential role of vaccination in this vulnerable group. Full article

Background/Objectives: Seasonal waves of respiratory viruses—including SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV)—continue to pose a global health burden and highlight the need for antiviral agents that are effective, safe, broadly active, affordable, and widely accessible. Current interventions are limited by the need for their early administration, the risk of resistance, their costs, and the restricted availability in large parts of the world. For certain natural products, such as European black elderberry (Sambucus nigra L.) fruit extract (ElderCraft^®; EC) and the seaweed-derived sulfated polymer iota-carrageenan (IC), antiviral activities against respiratory viruses, particularly IAV and SARS-CoV-2, have previously been shown. Here, we assessed the antiviral activity of IC and an anthocyanin-standardized EC extract against SARS-CoV-2, IAV, and RSV, either as monotherapy or in multiple-dose combinations. Methods: MDCKII cells were infected with IAV_PR8, human Calu-3 lung epithelial cells with the SARS-CoV-2 Omicron variant, and HEp-2 cells with RSV (A2 strain). Inhibitors were administered either by pre-incubation of cell-free virions prior to infection or, in separate time-of-addition experiments, during or post-infection. Viral replication was quantified by qRT-PCR or intracellular immunostaining. Cytotoxicity was evaluated using a neutral red uptake assay. Results: Most intriguingly, both EC and IC are able to neutralize virions derived from SARS-CoV-2, IAV, or RSV extracellularly in a dose-dependent manner. Notably, EC and IC alone exhibited strong anti-RSV activity, which was not reported previously. Most importantly, combined treatment with IC and EC caused a pronounced synergistic antiviral effect against the tested viruses, as confirmed by the Bliss independence model, without any detectable impact on cell viability. Finally, solutions prepared from matrix-standardized mono- or combi-lozenges, containing IC and/or EC in high or low doses, reproduced the antiviral and synergistic combination effects observed with the pure compounds. Conclusions: In summary, these findings support further development of EC and IC as a topically accessible, virion-neutralizing combination (e.g., lozenges) to provide additional protection against major respiratory viruses and potentially strengthen pandemic preparedness. Full article

Long COVID (LC), also referred to as post-acute sequelae of SARS-CoV-2 infection, is characterized by persistent symptoms originating 3 months following acute COVID-19, lasting for at least two months and frequently affecting individuals who initially experienced mild to moderate disease. The clinical spectrum is heterogeneous, involving respiratory, cardiovascular, neurological, renal, gastrointestinal, and endocrine systems, thereby posing substantial diagnostic and therapeutic challenges. Despite extensive investigation, the precise immunopathogenic mechanisms underlying LC remain incompletely defined. Accumulating evidence suggests that LC is driven by a multifactorial interplay of persistent viral antigen reservoirs, chronic immune activation, dysregulated innate and adaptive immune responses, autoimmunity, endothelial dysfunction, microvascular injury, and aberrant tissue repair. These systemic immune perturbations manifest variably across different organs, contributing to the diverse clinical phenotypes observed. However, mechanistic clarity is hindered by heterogeneity in study designs, limited longitudinal data, and the absence of standardized immunological profiling. This narrative review provides integrative insights into the immunopathogenesis of LC, synthesizing current evidence on systemic immune dysregulation and organ-specific immunological mechanisms. A conceptual framework is proposed to facilitate a structured understanding of this complex syndrome and to guide future research toward targeted immunomodulatory strategies. Full article

Context/Objectives: In patients with COPD (chronic obstructive pulmonary disease), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection represents an overlap of viral injury on a lung already affected by pathological mucus, altered mucociliary clearance, chronic inflammation, and impaired antiviral immunity. Methods: A focused narrative review (2020–2025) was conducted using clinical, experimental, and consensus evidence. The evidence was synthesized qualitatively, with priority given to cohort studies, meta-analyses, and mechanism-focused studies with clinical relevance. Results: Mucus obstruction (“mucus plugs”) is frequent in COPD (41–67%) and is associated with unfavorable outcomes. COPD also increases the risk of post-COVID respiratory sequelae. Bacterial coinfection at presentation is uncommon (3–5%), whereas secondary bacterial infections are more frequent (14–18%), especially in severe disease requiring intensive care, where VA-LRTI/VAP (ventilator-associated lower respiratory tract infection/ventilator-associated pneumonia) become predominant. Sepsis, whether viral or mixed, reflects disease severity and may contribute to functional decline and susceptibility to reinfections; however, the concept of a post-acute “sepsis legacy” in COPD after COVID-19 should currently be regarded as a clinically plausible but still emerging hypothesis rather than an established COPD-specific outcome. During recovery, acute exacerbation risk rises to 5.6% versus 3.9%, peaking in the first 30 days after severe disease (aHR ≈ 8.14). Persistent dyspnea and reduced DLCO (diffusing capacity for carbon monoxide) suggest ARDS-related injury, tissue remodeling, and microvascular dysfunction. Conclusions: In COPD, post-COVID respiratory sequelae result from the interaction of mucus, immunity, and infectious/sepsis-related complications. The first post-discharge month is a critical period requiring careful risk stratification and targeted follow-up. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells when the spike receptor-binding domain (RBD) engages angiotensin-converting enzyme 2 (ACE2). Cannabinoid scaffolds have recently been reported to bind S1/RBD, block spike-mediated membrane fusion, and modulate host inflammatory pathways, making them attractive candidates for entry inhibition. Here, we applied an integrated computational pipeline to prioritize cannabis-derived compounds as interfacial blockers of the RBD–ACE2 complex across variants. Eleven phytocannabinoids were docked into the wild-type (WT) RBD–ACE2 interface, identifying three cavities, with ligands preferentially occupying pocket 1. Complexes were subjected to triplicate 200 ns all-atom molecular dynamics (MD) simulations for WT, Delta, and Omicron BA.1 RBD–ACE2. Binding energetics were quantified using molecular mechanics/generalized Born surface area (MM/GBSA) and solvated interaction energy (SIE), and per-residue contributions were analyzed together with solvent-accessible surface area (SASA) and residue interaction networks. Among all compounds, cannabidiol (CBD) and cannabinol (CBN) were the only ligands that remained stably bound in pocket 1 for all variants. CBN showed the most favorable ligand–complex binding in WT, whereas CBD preserved favorable binding in Omicron BA.1 despite reduced interface burial, indicating that van der Waals/electrostatic complementarity and solvation, rather than surface coverage alone, govern affinity. Both ligands weakened modeled RBD–ACE2 binding by perturbing hot-spot residues centered on Y505 or N501Y in RBD and E37, A387, and R393 in ACE2. Overall, our results highlight CBD and CBN as tractable, variant-spanning interface disruptors and illustrate how MD-based free-energy calculations can support computational drug discovery against evolving viral protein–protein interfaces. Full article

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has revealed a complex interplay between respiratory and neurological manifestations. This study utilized K18-hACE2 transgenic mice to investigate the morphological, ultrastructural, and transcriptomic changes induced by SARS-CoV-2 infection in both lungs and brain tissues. Histopathological analysis at seven days post-infection revealed significant pulmonary damage characterized by interstitial pneumonia, alveolar septal thickening, with a marked inflammatory infiltrate predominantly consisting of neutrophils and lymphocytes, and an abnormal profile of type II pneumocytes. Concurrently, in the brain, we observed vasculitis, gliosis, and edema, indicating an inflammatory response and vascular compromise that can disturb the blood–brain barrier. In addition, gene expression in lung tissue presented increased CCL2, IL10, and GDDA45D in infected mice and the downregulation of proinflammatory genes. However, in brain tissue, the increased expression of CCL2, CASP1, IL6, IFNB1, and GDDA45G inflammatory genes was observed in infected K18-hACE2 mice. Full article

Background/Objectives: Persistent symptoms following SARS-CoV-2 infection pose a substantial burden in occupational settings. This study aimed to characterize symptoms following work-related SARS-CoV-2 infection and to assess their associations with sociodemographic and clinical factors. Methods: Data were obtained from a multicenter clinical registry of insured individuals referred for persistent symptoms 12 weeks after laboratory-confirmed work-related SARS-CoV-2 infection. Participants were assessed within a standardized post-COVID diagnostic program at six specialized clinics for occupational accident insurance in Germany. Persistent symptoms reported by ≥50% of participants were analyzed using generalized linear mixed models with random intercepts for center. Results: A total of 1511 participants (76.7% women; median age 54 years) were included, with a median interval of 16 months between infection and assessment. On average, participants reported ten persistent symptoms. The most frequent complaints were limited physical capacity (95.6%), concentration difficulties (78.8%), dyspnea (70.5%), exhaustion/tiredness (68.9%), and memory difficulties (67.5%). Individuals reporting more than ten acute symptoms had increased odds of persistent complaints (ORs between 2.1 and 4.66). Hospitalization was independently associated with persistent dyspnea (OR 1.62; 95%CI 1.17–2.25). Reinfections were linked to exhaustion and cognitive fatigue. Compared with Omicron, wild-type infection was associated with higher odds of concentration difficulties (OR 1.65; 95%CI 1.17–2.33). Comorbidities demonstrated symptom-specific associations. Conclusions: Among individuals with work-related SARS-CoV-2 infection, limited physical capacity and cognitive impairments were the most frequently reported symptoms, and higher acute symptom burden was strongly associated with the development of persistent symptoms. These findings support course-oriented evaluation and symptom-specific approaches in occupational disease assessment and management. Full article

Background: Long COVID presents a novel and emerging public health challenge. As the first point of contact, general practitioners (GPs) play a key role in diagnosing and coordinating the care of patients presenting with post-acute sequelae of COVID-19 (PASC), despite a lack of experience. This study aimed to identify the main difficulties encountered by GPs in Franche-Comté, France, in managing adult outpatients with long COVID. Methods: We conducted a cross-sectional survey using an anonymous online questionnaire, which contained 21 questions and was distributed to GPs in Franche-Comté, France. The survey assessed definition, diagnostic and therapeutic challenges in managing long COVID. Results: Among the 410 questionnaires distributed, 90 general practitioners (GPs) responded (response rate: 21.9%). The mean age of participants was 34 ± 10 years, and 64.4% were women (n = 58). Regarding knowledge of long COVID, three participants (3.3%) did not recognize it as a distinct clinical entity, while more than half (58.9%, n = 53) reported insufficient knowledge. The main challenges identified were therapeutic management (76.7%, n = 69) and diagnosis (75.6%, n = 68). Only 4.5% of respondents (n = 4) reported no difficulty in defining post-acute sequelae of SARS-CoV-2 infection (PASC). The most frequently reported diagnostic difficulty was distinguishing long COVID from differential diagnoses (93.3%, n = 83/89), particularly fibromyalgia (94.3%, n = 83/88). Only 37.1% of participants (n = 33/89) reported actively following up patients with PASC. During initial management, the main challenge was the difficulty in objectively assessing patients’ complaints using available diagnostic tools (80.7%, n = 67/83). Additionally, a large majority of GPs reported difficulties in addressing patients’ questions (86.7%, n = 72/83) and managing associated anxiety disorders (75.9%, n = 63/83). Conclusions: These findings highlight the immediate need to enhance GP training in Franche-Comté, France, in dealing with long COVID. Improvements such as harmonizing long COVID definitions, testing diagnoses, and strengthening interdisciplinary coordination are essential to provide coherent and patient-centered care for this disease. Full article

The development of novel antiviral nanomaterials is an important approach for addressing emerging viral threats. In this study, glycyrrhizic acid-modified gold nanoparticles (GA-Au NPs) were successfully synthesized and characterized, and their inhibitory effects against porcine reproductive and respiratory syndrome virus (PRRSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus were systematically evaluated. At non-cytotoxic concentrations, GA-Au NPs showed inhibitory activity against PRRSV in vitro. Stage-specific assays suggested that intracellular replication-related events were prominently affected, with additional inhibitory effects observed during adsorption, invasion, and release, whereas no direct virucidal activity was detected under the tested conditions. Furthermore, GA-Au NPs dose-dependently reduced SARS-CoV-2 pseudovirus infection-associated reporter signals in HEK-293T-ACE2 cells, supporting inhibitory activity in an additional viral model. In conclusion, GA-Au NPs represent a biocompatible antiviral nanomaterial with multi-stage inhibitory activity against PRRSV and inhibitory effects in a SARS-CoV-2 pseudovirus model, supporting their further evaluation as antiviral nanomaterials in enveloped virus-related models. Full article

SARS-CoV-2 continues to cause recurrent waves in the post-pandemic period, yet genomic data from Southeast Asia remain limited for several emerging Omicron lineages, including NB.1.8.1. In this study, routine acute respiratory infection (ARI) surveillance performed in Bangkok, Thailand, from January to December 2025 was integrated with real-time RT-PCR testing and complete spike-gene sequencing for lineage assignment and evolutionary analysis. Among 4756 ARI specimens, 473 (9.9%) tested positive for SARS-CoV-2. Positivity increased in late April, peaked in May (epidemiological week 21; 58.4%), and declined through late June. Lineage typing was successful for 165/473 positive samples (34.9%), identifying 16 Pango lineages. Early 2025 showed heterogeneous circulation, including XEC- and XEC.8-related lineages, whereas NB.1.8.1 predominated during the main wave, accounting for 92.4% of typed cases in May and 89.8% in June. No recombination signals meeting predefined criteria were detected in the spike dataset. The mean spike substitution rate was estimated at 1.11 × 10⁻³ substitutions/site/year (95% HPD, 9.13 × 10⁻⁴–1.31 × 10⁻³), and the major Thai-containing NB.1.8.1 clade had an estimated tMRCA of 17 July 2024. These findings show that routine ARI surveillance combined with spike-based genomics can provide timely insights into SARS-CoV-2 circulation, lineage replacement, and ongoing viral evolution in Thailand. Full article

Background: Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have generated major public health concerns worldwide. Young adults represent a critical group for viral transmission due to their high proportion of asymptomatic infections. Objective: To characterize the dynamics of SARS-CoV-2-specific antibodies in individuals aged 20–29 years from Bogotá, Colombia, across two longitudinal phases. Methods: Phase I assessed seroprevalence, seroconversion, spatial clustering, symptoms associated with seropositivity and antibody kinetics following natural infection. Phase II evaluated vaccine-induced antibodies, immune memory, and neutralizing capacity. Analyses included Functional Principal Component Analysis, survival analysis, clustering, and predictive modeling. Results: In Phase I, a seroprevalence of 15.59% (17/109 participants enrolled) was observed, while seroconversion among those who completed all six sampling points was 30.18% (16/53), with clusters of positive cases in different areas of Bogotá. The symptoms most associated with seropositivity included mucus hypersecretion, fever, and respiratory difficulty. Antibody responses were heterogeneous: naturally infected individuals generally showed high titers during the first 1–2 months, remaining detectable up to 4 months. The reduction in dimensionality suggested dominant humoral patterns, and clustering revealed two immune profiles differing in the risk of seroconversion. Predictive modeling indicated diverse antibody trajectories over 12 months. In Phase II (2024), three long-term immune memory clusters (low, medium, high) were observed; post-vaccination IgG titers were observed, although in most cases they lacked neutralizing activity. Conclusions: This longitudinal exploratory observational study provides an initial characterization of antibody dynamics in young adults, suggesting their potential epidemiological relevance and offering preliminary insights into post-infection and post-vaccination immunity. Full article

Background/Objectives: Cycle threshold (Ct) values from SARS-CoV-2 RT-PCR are widely reported in clinical practice, yet their interpretation in outpatient settings remains challenging due to substantial temporal and clinical variability. This study aimed to characterize day-by-day Ct distributions after symptom onset and to evaluate how symptom timing and fever severity inform diagnostic interpretation in primary care. Methods: We conducted a single-center retrospective study of 906 outpatients with COVID-19 who underwent saliva RT-PCR testing (January 2022–April 2023). Ct values were summarized according to days since symptom onset (Day 0–14). Peak self-reported temperature was categorized into 1 °C strata (36–40 °C), with temperature analyses restricted to patients tested on Day 0. Spearman’s correlation and multivariable linear regression with 95% confidence intervals were used to assess associations. Results: Ct values increased with longer intervals from symptom onset but demonstrated substantial variability within each day (Spearman’s ρ = 0.166, p < 0.001). On Day 0, higher temperature strata were associated with lower Ct values (p = 0.018). In multivariable analysis, days since onset, temperature category, sex, and age group were independently associated with Ct values, whereas vaccination doses and comorbidities were not. Conclusions: Incorporating symptom onset timing and fever severity may support more nuanced, context-based interpretation of Ct values in primary care, rather than reliance on isolated thresholds. Full article

Background. Autoimmune sclerosing cholangitis (ASC) is a rare clinical entity characterized by overlapping features of autoimmune hepatitis and primary sclerosing cholangitis. It predominantly affects pediatric patients. Therapeutic management is often complex, requiring a multidisciplinary and individualized approach, especially in the context of associated autoimmune diseases. Case presentation. We present the case of a female patient diagnosed at the age of 10 with ASC, for which immunosuppressive therapy with prednisone, azathioprine (AZA), and ursodeoxycholic acid (UDCA) was initiated, with an initially favorable course. One year later, following a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, the patient experienced reactivation of liver disease and subsequently developed ulcerative pancolitis (UC), for which 5-aminosalicylic acid (5-ASA) therapy was initiated. Due to repeated hepatic flares and/or colitis relapses, therapy was escalated successively to mycophenolate mofetil, tacrolimus, and eventually infliximab (IFX). Despite treatment, the liver disease progressed, culminating in liver cirrhosis. Our patient developed portal hypertension and esophageal varices, with two episodes of upper gastrointestinal bleeding requiring endoscopic band ligation. At the age of 14, the patient developed recurrent episodes of non-infectious ulcerative stomatitis. Biopsy of the lesions revealed non-specific chronic inflammation, unrelated to colitis activity (confirmed microscopic remission of UC). By exclusion, an adverse drug reaction was suspected, with AZA being the most likely cause. Following its discontinuation, the lesions resolved. Beyond the physiological and therapeutic aspects, the patient displays marked emotional fragility due to prolonged and repeated hospitalizations (18 out of 60 months), which have impacted treatment adherence. Conclusions. This case highlights the complexity of managing pediatric patients with multiple autoimmune diseases. The necessary combination of immunosuppressive therapies may lead to significant adverse effects and further complicate disease progression. Moreover, psychological components play a crucial role in treatment compliance and therapeutic success, emphasizing the need for an integrated approach that includes specialized psychological support. Full article

LL-37, a 37-amino acid human-derived antimicrobial peptide, was shown in our earlier clinical study to shorten the negative conversion time of the Omicron BA.5.1.3 variant of SARS-CoV-2. In this work, we investigated the broad mechanism of LL-37 by examining its inhibitory effect on non-enveloped virus Enterovirus 71 (EV71). LL-37 treatment dose-dependently reduced EV71 viral RNA abundance, suppressed virus-encoded protein expression, and decreased infectious titers, acting predominantly at a post-entry stage of the viral life cycle. Transcriptomic analysis revealed that the SH3 and cysteine-rich domain protein (Stac) was uniquely upregulated by LL-37 irrespective of EV71 infection. Short hairpin RNA (shRNA)-mediated Stac silencing significantly enhanced EV71 infection, while Stac overexpression markedly reduced it. Furthermore, we found that LL-37 activates the EGFR–ERK signaling pathway, leading to time-dependent upregulation of Stac expression. These findings uncover a novel host-directed mechanism by which LL-37 combats EV71 infection and suggests a potential therapeutic use of LL-37 against non-enveloped viral disease. Full article