Search Results (2,434)

Objective: The COVID-19 pandemic has strained healthcare systems and has been associated with substantial morbidity and mortality. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2), implicating dysregulation of the renin–angiotensin system (RAS) in COVID-19 pathophysiology. Measurement of circulating RAS components, including ACE and ACE2, may therefore provide an insight into disease severity and underlying mechanisms. Subjects and Methods: In this retrospective cohort study, 224 adults with PCR-confirmed COVID-19 were stratified by World Health Organization disease-severity criteria into asymptomatic, mild, mild-pneumonia, severe, and critical groups. Plasma ACE and ACE2 concentrations were quantified by ELISA. Demographic, clinical, and laboratory data were extracted from electronic medical records. Results and Conclusions: Increasing disease severity was associated with higher mortality, elevated body mass index, and higher viral load estimates. Severe and critical illness was characterized by leukocytosis with neutrophilia, marked lymphopenia, anemia, elevated inflammatory and coagulation markers, renal dysfunction, and hypoalbuminemia. Plasma ACE2 levels declined progressively with increasing severity and were significantly lower in patients with mild-pneumonia, severe, or critical illness compared with asymptomatic or mild cases, showing a strong inverse correlation with severity. In contrast, plasma ACE levels increased significantly with disease severity. The resulting increase in the ACE/ACE2 ratio indicates a progressive shift toward the pro-inflammatory arm of the RAS, providing mechanistic insight into the COVID-19 pathophysiology. Full article

Coronavirus infections pose a significant threat to both human and animal health, causing widespread morbidity, mortality, and substantial economic losses. While vaccines are crucial for prevention, their efficacy is often limited by the high mutation rate of these viruses. This underscores the urgent need for anti-coronavirus drugs, particularly broad-spectrum antiviral agents. In this study, we demonstrated for the first time that Biochanin A (BCA), a bioactive isoflavonoid found in legumes, exhibits broad-spectrum antiviral activity against coronaviruses. BCA potently inhibits porcine epidemic diarrhea virus (PEDV), as well as human coronaviruses HCoV-OC43 and HCoV-229E in vitro, with EC₅₀ values of 6.90, 2.80 and 15.4 μM, respectively. In a lethal mouse model of HCoV-OC43-induced encephalitis, oral administration of BCA (40–60 mg/kg) significantly improved animal survival and reduced cerebral viral loads. Mechanistic studies revealed that BCA upregulates the AMPK/Nrf2 signaling pathway, thereby increasing expression of the glutamate-cysteine ligase catalytic subunit (GCLC) and enhancing glutathione (GSH) biosynthesis. Our findings identify BCA as a promising host-directed antiviral agent and highlight its therapeutic potential against coronavirus infections. Full article

Background: This case report presents a 12-year-old male with vertically transmitted chronic hepatitis B virus (HBV) infection, exhibiting a rare pan-reactive serological profile (concurrent HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb positivity) alongside fluctuating low-level viremia (HBV DNA: 1.06 × 10² IU/mL to undetectable). Rigorous exclusion of technical artifacts confirmed the authenticity of this atypical serologic pattern, observed in <0.001% of the general population. Methods: Liver biopsy and immunohistochemical staining were performed to evaluate hepatic inflammation and fibrosis. HBV serological markers and viral load were quantified using commercial diagnostic kits, with longitudinal monitoring for 18 months. Results: Liver biopsy revealed Grade 2 inflammation with focal HBsAg/HBcAg expression, supporting immune-active chronic hepatitis B (CHB) despite partial seroconversion. The patient’s clinical course highlights key challenges in pediatric HBV management: (1) delayed immune reconstitution (18-month longitudinal HBeAg/HBeAb dynamics), (2) non-linear virologic-ALT correlation, and (3) diagnostic ambiguity in pan-positive serology—potentially reflecting S-gene escape mutants or transitional immune responses. Initiation of tenofovir disoproxil fumarate (TDF) achieved sustained virologic suppression, underscoring the importance of early antiviral therapy in pediatric CHB with atypical markers. Conclusions: This case provides preliminary insights into the complex interplay between viral evolution and immature host immunity, advocating for refined monitoring protocols integrating high-sensitivity HBV DNA, quantitative serology, and non-invasive fibrosis assessment in pediatric HBV care. Full article

Background/Objectives: Lamiaceae species are valuable sources of bioactive natural products, often associated with anti-infective properties. This study investigated chemical composition and bioactivities of dry hydroethanolic extracts and essential oils from Micromeria nervosa (Desf.) Benth. aerial parts from two localities. Methods: Extracts and essential oils were analyzed using LC-DAD-QTOF-MS/MS and GC-FID/MS, respectively. Antimicrobial activity was assessed against 14 strains (microdilution method), and antiviral activity against three viruses by determining cytopathic effects, viral titers (end-point dilution assay) and viral loads (qPCR/RT-qPCR). Cytotoxicity was evaluated on three cancer cell lines (MTT assay) and antioxidant potential using three colorimetric tests. Composition–activity correlation was statistically analyzed; in silico molecular docking/dynamics simulations were performed. Results: Thirty-five compounds were annotated in extracts, including 30 reported for the first time in this species, with rosmarinic acid as the main component. Essential oils contained 31 constituents, dominated by carvacrol. Newly detected phenolics included lithospermic acid and several salvianolic and clinopodic acids. Extracts and oils exhibited notable antibacterial activity, especially against five Gram-positive strains (MIC = 0.313–2.5 mg/mL), and oils showed marked anticandidal effects (MIC = 0.313–0.625 mg/mL) and enhanced cytotoxicity against colon, gastric and hypopharyngeal cancer cells (selectivity indices ≥ 1.66). Extracts displayed potent antiviral activity against human herpesvirus 1 (HHV-1) and adenovirus Ad5, reducing cytopathic effects and viral titers, with qPCR revealing decreased HHV-1 load. In silico analysis suggested HHV-1 glycoprotein D binding. Extracts also showed strong antioxidant potential. Conclusions: These findings demonstrate that M. nervosa is a rich source of compounds with antimicrobial/antiviral, cytotoxic and antioxidant activities, warranting further research. Full article

Objectives: To determine the incidence and outcomes of SARS-CoV-2 infection and to evaluate seroconversion rates and quantify antibody responses to COVID-19 vaccines in two cohorts of persons living with HIV at a possible higher risk of poor outcomes (HCV coinfection and those over the age of 65 years). Methods: We included participants from two established cohorts of persons living with HIV, those who were older than 65 years of age, and those with hepatitis C (HCV) co-infection. Four hundred and seventy-one participants completed questionnaires on SARS-CoV-2 infection and COVID-19 vaccine doses and submitted peripheral blood specimens for measuring antibody levels to COVID-19 antigens, full-length spike trimer, its receptor binding domain (RBD), and nucleocapsid protein (N) at 6-month intervals up to three visits between February 2021 and December 2024. Logistic and ordinal logistic regression models evaluated predictors of seroconversion and antibody levels. Results: Overall, 51% of participants developed a SARS-CoV-2 infection, but it was mild, with only nine requiring hospital admission and no deaths. Overall, 99% of tested specimens had antibodies above threshold to either spike or RBD proteins. Specimens that did not and those with lower antibody levels had testing earlier in the pandemic, and were from participants with fewer vaccine doses, and did not have natural infection. Age, depression, comorbidity, HCV co-infection, current substance use, CD4 count, or HIV viral load were predictive of antibody level. Those with hybrid immunity had higher antibody responses. Conclusions: In cohorts of persons with HIV-HCV coinfection and those who are ageing, we observed high rates of seroconversion to COVID-19 antigens. Antibody levels were higher among those with more vaccine doses, hybrid immunity, and later in the pandemic waves. Although 51% developed a breakthrough infection, outcomes were mild with no deaths. Full article

Highly pathogenic avian influenza virus (HPAIV) H5N1 has been detected in dairy cattle in the United States, with high viral loads observed in milk from infected animals. This raises public health concerns regarding potential transmission through exposure to raw milk. The sale of raw milk via vending machines represents a well-established distribution model in many European countries, including Switzerland. Although a notice must be posted on these milk vending machines stating that it is raw milk, together with appropriate processing instructions (heating to over 70 °C required, storage below 5 °C, consumption within 3 days), these notices are sometimes missing, and consumers often do not follow these guidelines. Over a four-month period, spanning from June 2025 to September 2025, 124 raw milk samples were collected from vending machines across Switzerland. Samples were screened for influenza A using reverse-transcription quantitative PCR (RT-qPCR). No samples tested positive for influenza A virus. The data from this study demonstrate the feasibility of implementing a sampling and detection system for HPAIV H5N1 in direct-to consumer raw milk samples and highlight the currently very low risk of HPAIV in raw milk samples sold via vending machines in Switzerland. Full article

Background/Objectives: This retrospective study investigates the prevalence and distribution of HCV genotypes among 233 genotyped patients from the Epirus region of Northwestern Greece from 2014 to 2024. Methods: Genotypes were detected by molecular diagnostic assays, and their association with demographic parameters and viral load was analyzed. Results: The most prevalent subtype was 3a (50.2%), especially among younger and male patients, followed by subtypes 1b and 1a. A statistically significant association was found between genotype and both age and sex, while genotype distribution did not significantly differ by national origin. Furthermore, subtype 6c-I was found only in a non-native case, suggesting a possible introduction of this rare strain. Viral load showed no significant difference by sex, genotype, or age group. A notable decline in HCV cases was documented during the COVID-19 pandemic, underscoring the impact of the public health crisis on HCV diagnosis. Despite the decreasing need for genotyping in the direct-acting antiviral (DAA) era, our findings support the continued molecular surveillance of circulating HCV strains. Conclusions: This is the first study to longitudinally assess HCV genotype dynamics over a full decade (2014–2024) in the Epirus region of Northwestern Greece, capturing trends during the COVID-19 era and documenting the emergence of rare genotypes. It contributes to the evolving knowledge of HCV epidemiology in Southeastern Europe. Full article

Cytomegalovirus (CMV) pneumonia presents diagnostic challenges in AIDS patients, as plasma monitoring often fails to reflect pulmonary viral burden. This retrospective study evaluated the prognostic value of bronchoalveolar lavage fluid (BALF) CMV DNA loads in 189 AIDS patients with pulmonary infections and CD4⁺ T cell counts < 200 cells/μL. CMV DNA in BALF and plasma was quantified to analyze associations with immune status and 90-day all-cause mortality. CMV detection was significantly more frequent in BALF (49.7%) than plasma (26.6%), indicating viral compartmentalization. An optimal BALF cutoff of 10,000 copies/mL was established for mortality prediction. Patients exceeding this threshold exhibited significantly lower CD4⁺ counts, increased mechanical ventilation requirements (34.4% vs. 11.5%), and prolonged hospital stays. Crucially, a BALF CMV load > 10,000 copies/mL was identified as an independent predictor of 90-day mortality (adjusted odds ratio = 3.78; 95% CI: 1.12–12.71). In conclusion, pulmonary CMV replication is prevalent and often compartmentalized in AIDS patients. A BALF CMV DNA load exceeding 10,000 copies/mL serves as a biomarker of profound immunosuppression and independently predicts poor clinical outcomes, highlighting the necessity of quantitative BALF monitoring for risk stratification. Full article

Porcine reproductive and respiratory syndrome virus genotype 1 (PRRSV-1), particularly the BJEU06-1-like subgroup, has shown increasing detection in China; however, the biological characteristics of newly emerging strains in southwestern regions remain insufficiently defined. Therefore, this study aimed to isolate and characterize a PRRSV-1 strain circulating in Southwestern China and to compare its biological properties and pathogenicity with those of a representative NADC30-like PRRSV-2 strain. In this study, a PRRSV-1 field strain (CDAC-SC2025) was isolated from a lung sample collected in Sichuan Province and characterized by immunofluorescence, full-genome sequencing, and maximum-likelihood phylogenetic analysis. Recombination was assessed using RDP4 and SimPlot (Baltimore, MD, USA). Pathogenicity was evaluated in newborn piglets following intranasal challenge, with monitoring of clinical signs, viremia, viral shedding, tissue viral loads, and histopathology. CDAC-SC2025 clustered within the BJEU06-1-like subgroup and showed the closest relationship to HENZMD-10 without detectable recombination. A three-amino-acid deletion (373–375 aa) was identified in nsp2. In vivo, CDAC-SC2025 induced fever, respiratory signs, growth retardation, and mortality, but the onset of death was delayed and lesion severity was lower than those caused by the NADC30-like strain DJY. Both strains exhibited predominant viral loads in the lung and tonsils, although quantitative differences were observed across tissues. Histopathology revealed moderate lesions in CDAC-SC2025-infected piglets compared with more severe multisystemic damage caused by DJY. These findings provide updated data on the biological properties of BJEU06-1-like PRRSV-1 circulating in southwestern China. Full article

Feline panleukopenia virus (FPV) is a major feline pathogen, but canine-derived FPV variants have recently been identified. Here, we compared the pathogenicity of a canine-derived FPV strain in cats with that of a lethal feline-derived FPV strain and evaluated the evolutionary significance of its NS1 mutations. Kittens infected with the canine-derived strain developed only mild, self-limiting diarrhea without fever or mortality, whereas those infected with the feline-derived strain developed severe disease and reached humane endpoints by 9 dpi. The canine-derived strain caused prolonged fecal shedding from 6 to 38 dpi but only low tissue viral loads (10¹–10³ copies/g), while the feline-derived strain reached markedly higher loads (10³–10⁶ copies/g), particularly in the ileum, jejunum, and lungs. Viral DNA levels in the lungs, ileum, caecum, and rectum were significantly higher in the feline-derived group. Sequence analysis identified four NS1 mutations, 115I, 132L, 247Q, and 595Q, which showed stepwise evolutionary accumulation and signatures of positive selection. These findings indicate that canine-derived FPV retains infectivity in cats but exhibits attenuated pathogenicity and reduced replication fitness, highlighting NS1 as a potential determinant of host adaptation. Full article

The coronavirus disease 2019 (COVID-19) pandemic altered the infection patterns of various pathogens; however, its impact on pediatric active Epstein–Barr virus (EBV) infection has not been sufficiently investigated in large-scale studies, and its long-term effects remain unexplored. We analyzed 57,403 pediatric patients from January 2018 to December 2024. Positivity rates of active EBV infection remained consistently elevated throughout the two-year period following the onset of the COVID-19 pandemic, significantly exceeding both pre-pandemic and during-pandemic levels (5329 [22.83%] vs. 1866 [13.55%] vs. 2188 [14.40%], p < 0.001), with concomitantly higher viral loads (median: 8.00 × 10³ vs. 1.78 × 10³ vs. 1.88 × 10³ copies/mL, p < 0.001). Post-pandemic, patients with EBV more frequently presented with pneumonia and allergic dermatitis, and the 6–11-year-old group accounted for a higher proportion of cases. This study reveals a prolonged surge of pediatric active EBV infection after the pandemic, characterized by sustained high prevalence, an age shift toward school children, and evolving clinical features. In the post-pandemic era, heightened and sustained attention should be paid to EBV infection in children, particularly among school-aged children. The sustained high prevalence of pediatric active EBV infection in the post-pandemic period warrants further investigation into its underlying causes. Full article

Background: This study evaluated the inter-method agreement of an in-house qualitative CMV real-time PCR assay for the detection of cytomegalovirus (CMV) DNA in various non-plasma clinical specimen types, in comparison with a commercially available comparator assay. Methods: In this prospective comparative study, 186 clinical specimens—including bronchoalveolar lavage fluid (BALF), stool, urine, colonoscopic biopsy, amniotic fluid, and intraocular fluid—were analyzed. A total of 166 samples with valid results from both test systems were included in the inter-method comparison. CMV DNA was detected using the in-house qualitative PCR assay in parallel with the comparator assay (artus^® CMV QS-RGQ kit). Agreement was assessed using positive percent agreement (PPA), negative percent agreement (NPA), overall percent agreement (OPA), and Cohen’s kappa coefficient (κ), in accordance with CLSI EP12-A2 recommendations. Results: Substantial overall inter-method agreement was observed when all specimens were evaluated collectively (κ = 0.66). Agreement metrics were highest in stool, urine, and invasive specimens, whereas BALF samples demonstrated comparatively lower agreement, reflecting potential matrix-related analytical variability. Conclusion: The laboratory-developed qualitative CMV PCR assay demonstrated substantial inter-method agreement with the comparator assay across multiple non-plasma specimen types. The findings highlight specimen-specific variability in qualitative CMV DNA detection and represent analytical concordance between two molecular assays rather than definitive clinical diagnostic accuracy or viral load quantification. Full article

Bovine viral diarrhea virus (BVDV), a globally persistent pathogen, causes bovine viral diarrhea-mucosal disease (BVD-MD), a contagious bovine disease posing significant pressures on both public health and economic development. Baicalin (BA), a flavonoid derived from Scutellaria baicalensis, exhibits broad antiviral activities but suffers from poor aqueous solubility and low bioavailability, limiting its therapeutic potential against BVDV. To address this limitation, we developed BA-loaded poly (ethylene gly-col)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (BA-PEG-PLGA NPs). While autophagy and NLRP3 inflammasome activation have been individually implicated in viral pathogenesis, their functional crosstalk during BVDV infection remains uncharacterized. Herein, we evaluated the antiviral efficacy of BA-PEG-PLGA NPs through integrated in vitro and in vivo experiments. We employed quantitative polymerase chain reaction (qPCR), transcriptome sequencing, Western blot analysis, immunofluorescence microscopy, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) to investigate the mechanisms by which BA and BA-PEG-PLGA NPs combat bovine viral diarrhea virus (BVDV) infection. We found that both free BA and BA-PEG-PLGA NPs effectively attenuated BVDV replication in vitro and in vivo; notably, the nano-formulation exhibited superior efficacy. Mechanistically, BA and its nano-formulation restored autophagy homeostasis, suppressed ROS overproduction, and blocked NLRP3 inflammasome activation and pyroptotic cell death effects comparable to the specific NLRP3 inhibitor MCC950. These findings establish the autophagy–NLRP3/pyroptosis axis as a critical pathogenic mechanism in BVDV infection and reveal that nano-formulated baicalin represents an antiviral strategy by coordinately targeting this axis. This work not only provides a translatable nanomedicine approach for BVDV control but also expands the mechanistic understanding of flavonoid-based interventions in viral inflammatory diseases. Full article

Background and Clinical Significance: Left atrial myxoma is the most common benign primary cardiac tumor and is associated with embolic and hemodynamic complications. Complete surgical excision is the treatment of choice, while postoperative cardiovascular rehabilitation is essential for functional recovery. Case Presentation: We report the case of a 75-year-old woman with arterial hypertension, dyslipidemia, and chronic venous insufficiency (Clinical–Etiological–Anatomical–Pathophysiological (CEAP) class 2), and chronic hepatitis B virus (HBV) infection who underwent surgical excision of a left atrial myxoma and was subsequently admitted three weeks postoperatively for phase II cardiovascular rehabilitation. The postoperative course was complicated by transient atrial fibrillation, peripheral edema, pleural effusion, and progressive purpuric lesions of the lower limbs. Laboratory and immunological evaluation revealed positive cryoglobulins, markedly elevated rheumatoid factor (1058 UI/mL) and IgM levels (715 mg/dL), reduced complement levels (C3, C4), normocytic normochromic anemia, microscopic hematuria, and elevated ALT (156 U/L), AST (142 U/L), total bilirubin (1.4 mg/dL), and INR (1.6), suggestive of hepatic inflammatory activity. HBV status was scheduled for evaluation through Gastroenterology referral (HBV DNA viral load, serological markers: HBsAg, HBeAg, anti-HBe), as our Cardiology Rehabilitation Clinic lacks the possibility of evaluation. After systematic exclusion of alternative etiologies, secondary cryoglobulinemic vasculitis in the context of chronic HBV infection with biochemical evidence of hepatic activity was considered the most plausible diagnosis. Conclusions: This case highlights the complexity of managing elderly patients after cardiac tumor surgery, particularly in the presence of systemic comorbidities. Early recognition of extracardiac complications and an individualized, multidisciplinary strategy are essential to optimize outcomes. Full article

Background and Objectives. Mother-to-child transmission (MTCT) or vertical transmission of human immunodeficiency virus (HIV) is largely preventable in settings where prevention of MTCT (PVT) strategies are consistently implemented. Romania represents a particular epidemiological context, as individuals from the historical pediatric HIV cohort have now reached reproductive age. This study assessed current PVT outcomes in northeastern Romania and explored the remaining circumstances in which transmission still occurs. Materials and Methods. We performed a retrospective observational analysis at the Regional HIV/AIDS Center of Iași (“Sfânta Parascheva” Clinical Hospital of Infectious Diseases), including all pregnant women living with HIV and their HIV-exposed infants followed between 2023 and 2025. Maternal data comprised age, place of residence, origin from the Romanian pediatric cohort, antiretroviral therapy (ART) adherence, and HIV RNA viral load in the third trimester. Obstetric characteristics, delivery mode, neonatal antiretroviral prophylaxis, and infant HIV RNA PCR results during follow-up up to 18–24 months were also evaluated. Results. A total of 61 HIV-positive pregnant women and 53 HIV-exposed infants were included. Viral suppression during pregnancy was documented in 59 women (96.7%), while two cases of detectable viremia in late pregnancy were linked to poor ART adherence. All women delivered by elective cesarean section, and all infants received neonatal antiretroviral prophylaxis, with Raltegravir added in selected higher-risk situations. Overall, MTCT was 3.8% (2/53). No transmission events were recorded in 2023 or 2024; both cases occurred in 2025 (15.4% of infants born that year) and exclusively in the context of maternal viremia. Women originating from the historical pediatric HIV cohort accounted for 31.1% (19/61) of pregnancies, and no transmission was observed among their infants. Conclusions. In northeastern Romania, PVT programs remain highly effective when maternal viral suppression is achieved. Residual transmission was confined to situations of maternal viremia driven by ART non-adherence, highlighting the continued importance of adherence support during pregnancy. Full article