Search Results (154)

Modern inpatient care generates irregular streams of heterogeneous clinical events, yet most predictive models require fixed feature matrices, predefined time windows, or discretization of continuous measurements. We developed CHaRT, a decoder-only autoregressive transformer designed to jointly forecast the identity of the next clinical event and, when applicable, its associated continuous value. CHaRT was trained and internally validated on structured electronic health record data from adult acute-care encounters across a 12-hospital health system in Minnesota from 2001 to 2025. The final corpus included 4,447,625 encounters from 1,301,502 patients and 701,556,877 non-padding clinical event tokens spanning vital signs, laboratory values, medications, diagnoses, microbiology, virology, imaging, fluids, and outcomes (ICU transfer or death). Encounters were split into training, validation, and test sets before vocabulary construction, normalization, and windowing. On the held-out test set, CHaRT achieved Top-1, Top-5, and Top-10 next-event accuracies of 51.61%, 87.34%, and 93.22%, respectively, with perplexity 4.50 and expected calibration error 0.0109. For numeric prediction, z-score MSE was 0.3812 for vital signs and 0.5713 for laboratory values. Seeded examples generated clinically coherent trajectories. Using model representations, a linear probe predicted deterioration (ICU transfer or in-hospital death) at a 6 h landmark with AUROC 0.95–0.97, indicating that learned representations transfer to downstream clinical risk prediction. Full article

The 9th National Congress of the Italian Society for Virology (SIV-ISV), entitled “One Virology—One Health”, took place in Turin at the Centro Congressi Lingotto from 22 to 24 June 2025. The meeting highlighted recent multidisciplinary and translational developments in virology, with a strong focus on the integration of the One Health perspective. Major themes included viral emergence and surveillance, genomic sequencing and bioinformatics, virus–host interactions, viral immunology and vaccines, structural and physical virology, environmental and food virology, zoonoses and animal infections, diagnostics and antiviral therapy, virus-based biotechnology and plant virology. The Congress aimed to: (i) bring together clinicians, basic researchers, veterinarians, environmental microbiologists, bioinformaticians, public-health professionals and industry to share methodologies and best practices; (ii) provide an interactive scientific environment promoting discussion and collaboration between senior investigators and trainees through plenaries, joint society sessions, invited talks, oral communications selected from abstracts, poster sessions, and mentoring panels; and (iii) identify priorities and inspire new research directions at the interface of human, animal and environmental health. More than 400 participants from national and international institutions attended the meeting, featuring distinguished plenary speakers, joint sessions with global networks, and numerous presentations of original unpublished data. This report summarizes the meeting’s scientific highlights, cross-disciplinary discussions, and proposed actions to strengthen One Health surveillance, computational infrastructures, and translational applications of viral biology. Full article

Respiratory syncytial virus (RSV) is considered the leading causative agent of acute lower respiratory infections in infants and young children worldwide, which makes it a major contributor to pediatric morbidity and mortality. Infants are especially susceptible to severe disease in early life, which underlines the urgent need for developing effective immunization strategies against this virus. However, the development of vaccines against RSV has long been associated with significant challenges. For example, initial attempts, especially those involving formalin-inactivated RSV, resulted in vaccine-enhanced respiratory disease upon subsequent infection, which set a significant safety obstacle for future vaccine candidates. Other challenges facing vaccine development against RSV include the short-lived immunity induced by natural infection, lack of clear correlates of immunity, and immune naivety in infants. Recent breakthroughs in structural virology and immunology have provided insights into protective immunity against RSV, especially regarding neutralizing antibodies that recognize the virus in its prefusion conformation of the viral F protein. Among promising vaccine candidates, intranasal live-attenuated vaccines have emerged as especially promising for infant immunization, especially considering their close mimicry of natural infection that can elicit systemic as well as mucosal immunity in the respiratory tract. A newly emerging approach for live-attenuated virus vaccine development is codon-pair deoptimization (CPD), which is based on synthetic recoding that reduces viral replicative capacity while maintaining intact protein sequences and structure. The preclinical results of CPD-based RSV candidates have provided evidence of such vaccines’ ability to elicit robust immunity while maintaining favorable safety profiles. This review addresses the major challenges associated with the development of effective RSV vaccines for infant immunization, with particular emphasis on lessons learned from previous vaccine failures and recent advances in RSV vaccine development, particularly CPD-based attenuation strategies. Full article

Background and Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder characterized by persistent or relapsing fatigue lasting at least six months, not alleviated by rest and not previously present. It is accompanied by post-exertional symptom exacerbation and non-restorative sleep. Fatigue is often disabling and reduces daily activity by more than 50%. This study aimed to evaluate the long-term frequency of somatic and psychiatric disorders in women previously diagnosed with ME/CFS and to describe the long-term clinical course, laboratory findings, and fatigue-related changes during a 16-year follow-up period. Materials and Methods: Sixteen years ago, 40 women diagnosed with ME/CFS according to then-current CDC criteria were enrolled at the Clinic for Infectious Diseases and the Center for Laboratory Medicine, University Clinical Center of Vojvodina. All participants provided informed consent. After 16 years, 20 women agreed to follow-up evaluation. At both time points, participants underwent structured questionnaires, clinical examination, psychological assessment, and comprehensive laboratory testing, including hematological, biochemical, endocrinological, and virological analyses. Fatigue severity was assessed using the FibroFatigue Scale (FFS) and the Multidimensional Assessment of Fatigue (MAF) scale. Results: During follow-up, 15% of participants were diagnosed with rheumatoid arthritis, 10% with cervical or breast cancer, 5% experienced premature myocardial infarction, 5% developed bronchial asthma, and 20% were diagnosed with clinical depression. Progression of ME/CFS was observed in 15%, while 5% reported infertility. Additionally, 15% developed arterial hypertension. Only 15% of participants did not report symptom worsening or new diagnoses. Conclusions: Over the 16-year follow-up, 85% of women with ME/CFS developed significant somatic or psychiatric conditions. These findings suggest that women diagnosed with ME/CFS may experience substantial long-term somatic and psychiatric disease burden, supporting the need for continued clinical monitoring and individualized follow-up. Full article

Porcine enteric coronaviruses (PECs), including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), remain major causes of neonatal diarrhea, dehydration, mortality, and economic loss in swine production. Despite substantial progress in vaccine development, durable field protection is still inconsistent. In this narrative review, this narrative review synthesizes current knowledge on PEC vaccine design from three connected perspectives: antigenic breadth, mucosal immunity, and translational evaluation. The economic and virological context of PEC vaccine development is first summarized, including the recurrent production burden of PECs, coronavirus genome organization, structural proteins, and the central role of the spike protein in receptor engagement, membrane fusion, and neutralizing antibody induction. Key issues are then discussed, including how spike diversity, conformational stability, epitope accessibility, glycan shielding, and antigen matching influence protective breadth; why intestinal secretory IgA, mucosal immune-cell trafficking, local memory responses, and lactogenic immunity should be prioritized as biologically relevant endpoints; and how delivery route, adjuvant selection, and platform design shape response quality. Current evidence on recombinant protein, viral-vectored, nanoparticle, virus-like particle, probiotic, plant-derived, and mRNA-based approaches is compared with attention to both promise and current evidentiary and translational limitations. The available literature suggests that future progress in PEC vaccinology is likely to depend less on platform novelty alone than on integrated vaccine designs that align antigen selection, mucosal delivery, maternal–neonatal protection, heterologous challenge, manufacturability, and field applicability. Full article

Zika virus (ZIKV) infection during pregnancy is a critical driver of Congenital Zika Syndrome (CZS), yet the mechanisms of pathogenesis at the placental barrier remain incompletely understood. This article is a translational, observational, and experimental study combining clinical placental analyses, placental explants cultures and in vivo murine model to investigate the mechanisms involved in ZIKV infection. We evaluate the histopathological analyses to verify presence of inflammation in ZIKV-infected human placentas from newborns with CZS and without CZS (N-CZS), identifying more intense Hofbauer cell hyperplasia, villitis and decidual inflammation in CZS group. Moreover, placental immunohistochemistry analyses identified decreased TLR4 expression in the villi and reduced TNF and IL-10 levels across placental layers of CZS group. Next, we investigated the effects of inflammation on viral replication and explored whether the flavonoid Naringenin (NGN) could modulate this inflammation. Using a placental villous explant model, we verified that inflammation induced by LPS exacerbates viral replication and pathological markers. Notably, treatment with the NGN rescued the inflammatory and virological outcomes. These findings were further validated in a murine model of congenital infection, where NGN administration alleviated microcephaly-related structural alterations in ZIKV-exposed neonates. Our results indicate that placental inflammation is a key provocateur of ZIKV replication and subsequent fetal brain malformation. Furthermore, we identify NGN as a promising bifunctional antiviral and anti-inflammatory candidate for mitigating the developmental impacts of ZIKV infection. Full article

Although SARS-CoV-2 has been extensively studied from clinical, virological, and diagnostic perspectives, the problem of accurate automatic semantic segmentation of SARS-CoV-2 particles in electron microscopy images remains inadequately explored. Existing studies have largely focused on virus detection, classification, morphometry, or conventional image analysis, while comparatively little attention has been paid to pixel-level delineation of viral structures using specialised deep learning segmentation frameworks. To address this gap, we propose here a deep learning system based on convolutional neural networks (CNNs) combined with image processing techniques to establish semantic segmentation tools for the automatic identification of SARS-CoV-2. Our approach utilises the super-Euclidean pixels method as an intermediate layer within the CNN for semantic segmentation. We then compare its performance against the gradient vector flow (GVF) and Poisson inverse gradient (PIG) segmenters. The proposed CNN model surpassed the traditional GVF and PIG segmentation models, achieving the following metrics (mean ± variance): Dice similarity coefficient (DSC) = 0.9345 ± 0.0006; intersection over union (IoU) = 0.8782 ± 0.0018; sensitivity/true positive rate (TPR) = 0.9373 ± 0.0018; specificity/true negative rate (SPC) = 0.9517 ± 0.0012; accuracy = 0.9449 ± 0.0004; area under the ROC curve (AUC) = 0.9446 ± 0.0431; and Cohen’s Kappa = 0.9137 ± 0.0011. This method enables virologists to employ an automatic CNN-based segmentation tool for detecting SARS-CoV-2 and demonstrates superiority over GVF and PIG. Full article

In 2023, Cyprus experienced a large-scale epizootic of feline infectious peritonitis (FIP) temporally associated with the emergence of a novel feline coronavirus, FCoV-23. While molecular investigations have elucidated the recombinant origin of FCoV-23, field-based clinical and other epidemiological data from FIP cases reported during the epizootic period were needed to characterize the outbreak better. A prospective study was conducted using a structured 31-item questionnaire embedded in veterinary management software to characterize FIP cases diagnosed during the epizootic period (late 2022–2025). Data were voluntarily submitted by registered veterinarians across Cyprus. Cases were included based on a clinical diagnosis of FIP; virological confirmation of FCoV-23 infection was not required for inclusion. Data from 68 FIP cases reported by 22 clinics (response rate 21.0%) were analyzed. Affected cats were older than typically reported for FIP (mean age 3.9 years; median 3.0; range 0.4–12.9 years; SD 3.41). Most cases were documented in Limassol (51.5%) and Nicosia (25.0%). The most frequently reported clinical signs were non-specific, like anorexia (60.3%) and weight loss (54.4%), while a variety of neurological and mental manifestations were documented in 35.3% of cases. An albumin-to-globulin ratio < 0.8 was observed in 86.8% of tested cats. Antiviral therapy (GS-441524 or molnupiravir) was administered in 92.2% of cases, with reported clinical improvement of 88.9%. These findings demonstrate the value of questionnaire-based surveillance in documenting outbreak-associated FIP patterns. Although individual cases were not uniformly confirmed as FCoV-23 infections, the increased proportion of neurological presentations among FIP cases reported during the epizootic period supports previous molecular evidence suggesting that neurological involvement was associated with FCoV-23 circulation. Full article

Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b continues to circulate globally across wild birds, poultry, and an expanding range of mammalian hosts, highlighting the need for antiviral strategies that address the animal–environment–human interface. The influenza A polymerase acidic (PA) endonuclease, a key enzyme in viral transcription, represents a conserved antiviral target across host species. In this study, we present a computational prioritization framework integrating homology modeling, molecular docking, molecular dynamics simulations, and physicochemical filtering to identify candidate PA endonuclease inhibitors relevant to a One Health context. Homology models of contemporary H5N1 clade 2.3.4.4b PA sequences were constructed based on the crystallographic template 6FS8 and used for cross-host docking against a targeted ligand library. Docking analysis identified baloxavir, a reference inhibitor, and entecavir, a nucleoside analog, as compounds of interest, with entecavir demonstrating favorable binding behavior, particularly in the poultry-associated model. Molecular dynamics simulations of the poultry PA–entecavir complex indicated stable interaction over 170 ns, supported by low structural deviation and favorable binding free energy (ΔG ≈ −85 kJ/mol). Physicochemical profiling suggested that entecavir possesses properties such as high polarity and predicted aqueous solubility, which were considered within the translational filtering step of this computational workflow. However, these properties do not establish antiviral efficacy or practical suitability for field use. The study provides a structured framework for integrating cross-host structural analysis with basic translational considerations, supporting the identification of candidate compounds for further biochemical and virological evaluation within the context of H5N1 control. Full article

Located on the traditional and ancestral homelands of the Arapaho, Cheyenne, and Ute Nations, Colorado State University’s Mountain Campus hosted the 25th Annual Rocky Mountain Virology Association meeting. The three-day event, held from 26 September to 28 September 2025, welcomed 152 participants focused on the following topics: viruses, prions, immunology, transmission, structural biology, and vector biology. This year’s Randall Jay Cohrs Keynote Presentation summarized ongoing research on viral glycoproteins in relation to viral entry and assembly. Understanding the role of viral glycoproteins is essential in vaccine and antiviral development for enveloped RNA viruses. Alongside rigorous scientific discourse and networking, attendees made the most of their time by hiking amidst beautiful fall colors, wildlife, and young aspens starting the forest anew. On behalf of the Rocky Mountain Virology Association, this report summarizes select presentations from the 25th annual meeting. Full article

Coinfection between hepatitis C virus (HCV) and human T-lymphotropic virus 1/2 (HTLV-1/2) remains poorly investigated in the Northern Region of Brazil despite its clinically important condition. The objective of this study was to determine the prevalence and describe the epidemiological and behavioral risk factors for HCV/HTLV-1/2 coinfection in Belém, Pará. This observational, descriptive, and cross-sectional study analyzed 192 samples from patients previously diagnosed with HCV: 127 participants recruited between May 2023 and June 2025 and 65 samples previously stored in the Virology Laboratory of UFPA. Data were collected through a structured survey. Serological screening for HTLV-1/2 was performed by enzyme-linked immunosorbent assay (ELISA) and confirmed by INNO-LIA and molecular biology (qPCR). HCV/HTLV-1/2 coinfection was observed in 4 individuals (2.1%), of whom 1.6% had HCV/HTLV-1 coinfection and 0.5% HCV/HTLV-2. There was no statistically significant association when comparing the sociodemographic, clinical characteristics, or risk factors of HCV monoinfected and HCV/HTLV-1/2 coinfected individuals. Although the results show a low prevalence of HTLV-1/2 and HCV coinfection in Belém do Pará, they still reinforce the importance of including HTLV in testing protocols for patients with hepatitis C in the North region of Brazil. Full article

People living with HIV (PLWH) receiving effective antiretroviral therapy (ART) continue to exhibit chronic immune activation and systemic inflammation despite virological suppression. The viral envelope glycoprotein gp120, which binds the CD4 receptor and mediates viral entry, has been implicated in pro-inflammatory and pro-apoptotic effects in neuronal and endothelial cells. Although gp120 is expressed on the viral surface, its oligomeric structure and its ability to form immune complexes with circulating antibodies may reduce the sensitivity of standard detection assays in serum. Soluble gp120 has been associated with increased levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as chemokines. These mediators may contribute to blood–brain barrier dysfunction, endothelial injury, vascular smooth muscle alterations, and subsequent neurodegenerative and cardiovascular complications. Importantly, gp120 shedding may persist due to viral reservoirs and intermittent reactivation, even during ART. Fostemsavir inhibits the interaction between gp120 and CD4, preventing viral entry and potentially limiting gp120-mediated pathogenic effects. Beyond antiviral activity, this mechanism suggests a potential role in attenuating gp120-mediated inflammation. This review discusses the biological effects of gp120 and the rationale for targeting it therapeutically in PLWH. Full article

Background: Congenital cytomegalovirus (cCMV) infection is one of the most common congenital infections worldwide and the leading cause of non-genetic sensorineural hearing loss. Although less frequent in preterm infants, cCMV may significantly worsen outcomes in an already vulnerable population. The risks and benefits of antiviral therapy in extremely preterm neonates remain unclear, as this group is largely excluded from clinical trials. Case presentation: We report a case of symptomatic cCMV infection in an extremely preterm infant born at 26 weeks and 2 days of gestation to a mother with primary CMV infection during the second trimester. High CMV viral loads were detected in urine and plasma shortly after birth. On day of life (DOL) 3, respiratory deterioration required intubation, with radiological findings consistent with CMV pneumonia and positive bronchoaspirate samples. Intravenous ganciclovir was initiated on DOL 16 and administered for six weeks, followed by oral valganciclovir for six months. Treatment was associated with a favourable clinical and virological response and no significant hematological toxicity. Ophthalmologic and audiological evaluations were normal. Neurodevelopmental assessment with Bayley III at one year of corrected age demonstrated age-appropriate performance across all domains. Discussion: A structured literature review identified 10 case reports, including 13 extremely preterm infants treated for cCMV infection. Antiviral dosing regimens were heterogeneous. The most frequent manifestations prompting treatment were laboratory abnormalities (92.3%), particularly thrombocytopenia and leukopenia or neutropenia. Neuroimaging abnormalities and intrauterine growth restriction or small for gestational age were each reported in 53.8% of cases. Long-term neurodevelopmental outcomes were normal in 38.5% of infants. Conclusions: Antiviral therapy for cCMV infection with ganciclovir and valgancyclovir in premature neonates is feasible and safe with careful monitoring, and appears to provide benefits. Nevertheless, well-designed studies that include pharmacokinetics and pharmacodynamics, virologic monitoring, and long term outcomes of development, vision and hearing are urgently needed. Full article

Background: Advanced HIV disease (AHD) remains highly prevalent and is associated with increased morbidity and mortality. Missed opportunities for early diagnosis continue to represent a major public health challenge. Methods: We conducted a multicenter retrospective cohort study including antiretroviral-naive people with HIV (PWH) presenting with AHD (CD4 < 200 cells/µL and/or AIDS) diagnosed between 1 January 2019 and 31 December 2024 in four Italian infectious diseases units. Demographic, clinical and viro-immunological data were collected at baseline and during follow up. Information on healthcare contacts, HIV-related symptoms, and prior HIV testing in the two years preceding diagnosis was obtained through structured interviews. Results: Among 658 newly diagnosed participants with HIV, 224 (34%) presented with AHD, of whom 54% presented with AIDS. Most participants (86.2%) had never undergone HIV testing before diagnosis. In the year preceding diagnosis 29.3% accessed healthcare services for symptoms compatible with HIV infection without being tested for HIV. At one year, 84.2% achieved virological suppression, with a median CD4 count of 260 cells/µL. Overall loss to follow-up was 27.2%. Five-year survival was significantly higher in non-AIDS presenters compared with AIDS presenters (100% vs. 85%, p = 0.005). Conclusions: Missed diagnostic opportunities remain frequent among PWH presenting with AHD, despite prior healthcare contacts. Wider implementation of indicator condition-guided HIV testing is urgently needed to reduce late diagnosis and improve long-term outcomes. Full article

Well established long ago for bacterial and fungal detection, Matrix-Assisted Laser Desorption/Ionization–Time of Flight (MALDI-TOF) technique is not so well established in the virology field, and taking care of its advantages (speed, precision and low cost), this can be a powerful method for viral identification. To explore the feasibility and potential of MALDI-TOF for viral detection, this study shows the development of an in-house spectral library including several uninfected cell cultures and cultures infected with different clinically relevant viruses, such as SARS-CoV-2. This library was applied to the identification of viral infections directly on cell cultures, assessing the ability of the technique to discriminate between infected and non-infected profiles. Additionally, bioinformatic analyses were conducted to evaluate the structure, specificity, and reproducibility of the in-house library, and to understand its strengths and limitations. Sensitivity and specificity of the method were estimated by testing multiple culture batches from selected viruses included in the library. Together, these results provide a deeper understanding of the performance and applicability of MALDI-TOF in the virological context, highlighting its potential as a valuable research platform and a prospective tool for clinical viral detection. Full article