Search Results (4,688)

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the etiologic agent that causes the coronavirus disease (COVID-19) identified in Wuhan, in 2019. Men are more prone to developing severe manifestations than women, suggesting a possible crucial role of sex hormones. 17,β-Estradiol (E2) and 1,25 α dihydroxyvitamin D₃ (calcitriol) act upon gene pathways as immunomodulators in several infectious respiratory diseases. In this study, we aimed to evaluate the influence of E2 and calcitriol on the VSV-based pseudovirus SARS-CoV-2 and SARS-CoV-2 infection in vitro. We infected Vero E6 cells with the recombinant VSV-based pseudovirus SARS-CoV-2 and the SARS-CoV-2 viruses according to the pre-treatment and pre–post-treatment models. The Angiotensin-Converting Enzyme 2 (ACE2) and Vitamin D Receptor (VDR) gene expression did not change under different treatments. The VSV-based pseudovirus SARS-CoV-2 infection showed a significant decrease in the focus-forming unit count in the presence of E2 and calcitriol (either alone or in combination) in the pre-treatment model, while in the pre–post-treatment model, the infection was inhibited only in the presence of E2. Th SARS-CoV-2 infection highlighted a decrease in viral titres in the presence of E2 and calcitriol only in the pre–post-treatment model. 17,β-Estradiol and calcitriol can exert an inhibitory effect on SARS-CoV-2 infections, demonstrating their protective role against viral infections. Full article

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

Background/Objectives: This retrospective multicenter study, conducted within the ORCHESTRA Project, investigated SARS-CoV-2 reinfections among 5777 healthcare workers (HCWs) from four University Hospitals (Modena, Verona, Padova and Trieste) in northern Italy, aiming to assess the risk of reinfection and its determinants, comparing the clinical characteristics of reinfections with those of first infections, and examining the impact of preventive measures and vaccination strategies. Methods: HCWs completed an online questionnaire between June and August 2022. The survey collected demographic, occupational, and clinical data, including information on first infections and reinfections. Statistical analyses were performed using SPSS 28.0, through bivariate and multivariate approaches. Results: Response rates were 41.8% for Modena, 39.5% for Verona, 17.9% for Padova, and 17.4% for Trieste. Among the respondents, 4.8% (n = 276) experienced 2 infections and 0.5% (n = 27) reported 3 infections, out of a total of 330 reinfection cases. Additionally, 43.0% (n = 2787) reported only one infection, while 51.5% were never infected. Reinfection rates increased across five study phases (based on the epidemiological context), likely due to the emergence of new SARS-CoV-2 variants. A booster vaccine dose significantly reduced reinfection risk. Higher reinfection risk was found among HCWs aged ≤30 years, those with chronic respiratory diseases, and those working in COVID-19 wards, particularly nurses and allied health professionals. Reinfections were associated with a lower frequency of symptoms both during the period of swab positivity and after a negative swab, as well as with a shorter duration of swab positivity. No significant differences in symptom duration were found between first infections and reinfections. Conclusions: Despite its limitations, the online questionnaire proved a useful tool. Natural infection and vaccination reduced both reinfection risk and symptom severity. Prior infections should be considered in planning vaccination schedules and prioritizing HCWs. Full article

Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have documented complications in both expectant mothers and their infants following infection. Methods: In our previous works, we provided scientific evidence of the bacteriophage behavior of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). This demonstrated that a well-defined combination of two antibiotics, amoxicillin and rifaximin, is associated with the same statistics for subjects affected by severe cases of SARS-CoV-2, regardless of vaccination status. We considered the few cases in the literature regarding the management of pregnancies infected with SARS-CoV-2, as well as previous data published in our works. In this brief case series, we present two pregnancies from the same unvaccinated mother—one prior to the COVID-19 pandemic and the other during the spread of the Omicron variant—as well as one pregnancy from a mother vaccinated against COVID-19. We describe the management of acute maternal infection using a previously published protocol that addresses the bacteriophage and toxicological mechanisms associated with SARS-CoV-2. Results: The three pregnancies are compared based on fetal growth and ultrasound findings. This report highlights that, even in unvaccinated mothers, timely and well-guided management of symptomatic COVID-19 can result in positive outcomes. In all cases, intrauterine growth remained within excellent percentiles, and the births resulted in optimal APGAR scores. Conclusions: This demonstrates that a careful and strategic approach, guided by ultrasound controls, can support healthy pregnancies during SARS-CoV-2 infection, regardless of vaccination status. Full article

Artificial intelligence (AI) techniques—ranging from hybrid mechanistic–machine learning (ML) ensembles to gradient-boosted decision trees, support-vector machines, and deep neural networks—are transforming the management of seasonal influenza, respiratory syncytial virus (RSV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptom-based triage models using eXtreme Gradient Boosting (XGBoost) and Random Forests, as well as imaging classifiers built on convolutional neural networks (CNNs), have improved diagnostic accuracy across respiratory infections. Transformer-based architectures and social media surveillance pipelines have enabled real-time monitoring of COVID-19. In HIV research, support-vector machines (SVMs), logistic regression, and deep neural network (DNN) frameworks advance viral-protein classification and drug-resistance mapping, accelerating antiviral and vaccine discovery. Despite these successes, persistent challenges remain—data heterogeneity, limited model interpretability, hallucinations in large language models (LLMs), and infrastructure gaps in low-resource settings. We recommend standardized open-access data pipelines and integration of explainable-AI methodologies to ensure safe, equitable deployment of AI-driven interventions in future viral-outbreak responses. Full article

In recent years, the persistent emergence of novel infectious pathogens (epitomized by the global coronavirus disease-2019 (COVID-2019) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has propelled nucleic acid testing (NAT) into an unprecedented phase of rapid development. As a key technology in modern molecular diagnostics, NAT achieves precise pathogen identification through specific nucleic acid sequence recognition, establishing itself as an indispensable diagnostic tool across diverse scenarios, including public health surveillance, clinical decision-making, and food safety control. The reliability of NAT systems fundamentally depends on reference materials (RMs) that authentically mimic the biological characteristics of natural viruses. This critical requirement reveals significant limitations of current RMs in the NAT area: naked nucleic acids lack the structural authenticity of viral particles and exhibit restricted applicability due to stability deficiencies, while inactivated viruses have biosafety risks and inter-batch heterogeneity. Notably, pseudovirus has emerged as a novel RM that integrates non-replicative viral vectors with target nucleic acid sequences. Demonstrating superior performance in mimicking authentic viral structure, biosafety, and stability compared to conventional RMs, the pseudovirus has garnered substantial attention. In this comprehensive review, we critically summarize the engineering strategies of pseudovirus platforms and their emerging role in ensuring the reliability of NAT systems. We also discuss future prospects for standardized pseudovirus RMs, addressing key challenges in scalability, stability, and clinical validation, aiming to provide guidance for optimizing pseudovirus design and practical implementation, thereby facilitating the continuous improvement and innovation of NAT technologies. Full article

Background/Objectives: In late 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a pandemic called the ‘coronavirus disease 2019’ (COVID-19). After the acute SARS-CoV-2 infection, many individuals (up to 33%) complained of unexplained symptoms involving multiple organ systems and were diagnosed as having Long COVID-19 (LC-19). Currently, LC-19 is inadequately defined, requiring the formation of consistent diagnostic parameters to provide a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy. LC-19 represents a significant burden on multiple levels. The reduced ability of workers to return to work or compromised work efficiency has led to consequences at national, economic, and societal levels by increasing dependence on community services. On a personal scale, the isolation and helplessness caused by the disease and its subsequent impact on the patient’s mental health and quality of life are incalculable. Methods: In this paper, we used Walker and Avants’ eight-step approach to perform a concept analysis of the term “Long COVID-19” and define its impact across these parameters. Results: Using this methodology, we provide an improved definition of LC-19 by connecting the clinical symptomology with previously under-addressed factors, such as mental, psychological, economic, and social effects. This definition of LC-19 features can help improve diagnostic procedures and help plan relevant healthcare services. Conclusions: LC-19 represents a complex and pressing public health challenge with diverse symptomology, an unpredictable timeline, and complex pathophysiology. This concept analysis serves as a tool for improving LC-19 definition, but it remains a dynamic disease with evolving diagnostic and therapeutic approaches, requiring deeper investigation and understanding of its long-term effects. Full article

Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute lung injury seen in patients. In this study, we describe the predominance of the innate immune response in hamsters inoculated with four different SARS-CoV-2 variants, underscoring phenotypic differences among them. Severe inflammatory lung injury was chronologically associated with acute and significant weight loss, mainly in animals inoculated with A.2 and Delta variants. Omicron-infected animals had lower overall histopathology scores compared to other variants. We highlight the central role of endothelial injury and activation in the pathogenesis of experimental SARS-CoV-2 infection in hamsters, characterised by the presence of proliferative type I and type II pneumocytes with abundant surfactant expression, thereby maintaining hyperinflated alveolar fields. Additionally, there was evidence of intrapulmonary lymphatic vessel proliferation, which was accompanied by a lack of detectable microthrombosis in the lung parenchyma. However, white microthrombi were observed in lymphatic vessels. Our findings suggest that the physiological compensatory mechanisms that maintain respiratory homeostasis in Golden Syrian hamsters prevent severe respiratory distress and death after SARS-CoV-2 infection. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has posed substantial health threats and triggered widespread global economic disruption. The nucleocapsid (N) protein of SARS-CoV-2 is not only a key structural protein but also instrumental in mediating the host immune response, contributing significantly to inflammation and viral pathogenesis. Due to its immunogenic properties, SARS-CoV-2 N protein also interacts with host factors associated with various pre-existing inflammatory conditions and may possibly contribute to the long-term symptoms suffered by some COVID-19 patients after recovery—known as long COVID. This review provides a comprehensive overview of recent advances in elucidating the biological functions of the N protein. In particular, it highlights the mechanisms by which the N protein contributes to host inflammatory responses and elaborates on its association with long COVID and pre-existing inflammatory disorders. Full article

Background: This study examined risk factors for syndrome novel coronavirus 2 virus (SARS-CoV-2) infection and self-reported adherence to infection prevention and control (IPC) measures among healthcare workers (HCWs) at a hospital in Thailand near the Myanmar border. Methods: From March to July 2022, HCWs aged ≥ 18 with COVID-19 exposure at Mae Sot General Hospital completed a questionnaire on IPC adherence, training, and COVID-19 knowledge. Nasopharyngeal samples were collected bi-weekly for SARS-CoV-2 testing. A mobile application was used for real-time monitoring of daily symptoms and exposure risks. Chi-square, Fisher’s exact tests, and log-binomial regression were performed to investigate association. Results: Out of 289 (96.3%) participants, 27 (9.9%) tested positive for SARS-CoV-2, with cough reported by 85.2% of cases. Nurse assistants (NAs) had a higher risk of infection (adjusted relative risk [aRR] 3.87; 95% CI: 0.96–15.6). Working in inpatient departments (aRR 2.37; 95% CI: 1.09–5.15) and COVID-19 wards (aRR 5.97; 95% CI: 1.32–26.9) was also associated with increased risk. While 81.7% reported consistent hand hygiene, 37% indicated inadequate IPC knowledge. Conclusions: HCWs, especially NAs and those in high-risk departments, should receive enhanced IPC training. Real-time digital monitoring tools can enhance data collection and HCW safety and are likely to be useful tools for supporting surveillance and data collection efforts. Full article

Background: The long-term impact of SARS-CoV-2 infection on pulmonary function remains insufficiently characterised, particularly among individuals who have experienced mild or asymptomatic disease. This study aimed to assess spirometric changes over a three-year period and evaluate potential associations with demographic and clinical variables. Methods: We retrospectively analysed spirometry data from 103 healthcare workers (HCWs) who underwent pulmonary function tests at three time points: before the pandemic (Time 0), one year post-pandemic (Time 1), and two years post-pandemic (Time 2). Linear regression models were employed to evaluate the impact of various factors, including age, BMI, gender, smoking status, history of SARS-CoV-2 infection, vaccination status prior to infection, and the number of infections, on changes in FVC and FEV₁. Results: A statistically significant decrease in both FVC and FEV₁ were observed at Time 1 and Time 2 compared to baseline (p < 0.05). Smoking habits were significantly associated with a greater decline in both FVC and FEV₁. Multiple infections were associated with larger reductions in FVC at Time 1. No significant associations were found with age, gender, BMI, or vaccination status. Even in the absence of severe symptoms of the disease, healthcare workers exhibited a measurable decline in pulmonary function over time. Smoking and reinfection emerged as relevant factors associated with reduced lung capacity. Conclusions: These findings emphasise the need for ongoing respiratory monitoring in occupational settings and the importance of targeted preventive measures. Full article

Background: Malnutrition is associated with adverse clinical and economic outcomes. We recently reported that the hospital mortality rate in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected inpatients was higher in malnourished patients than in those without malnutrition. The present study aimed to determine if SARS-CoV-2-infected inpatients who received oral nutrition supplementation (ONS) had improved survival. We performed a retrospective cohort study including 37,215 adults (aged 18 and older) admitted with COVID-19 to five Johns Hopkins–affiliated hospitals between 1 March 2020, and 31 March 2023. Malnutrition risk was initially screened using the Malnutrition Universal Screening Tool (MUST), with cases subsequently confirmed by registered dietitians via a standardized, validated assessment protocol. Logistic regression analysis predicting hospital mortality examined the association of ONS with hospital survival in SARS-CoV-2-infected inpatients, incorporating covariates and weights for ONS receipt. Results: Malnutrition was an independent predictor of higher hospital mortality from COVID-19 illness. The prevalence of malnutrition among adult inpatients with SARS-CoV-2 infection in our cohort was 15.22%. Inpatient adults with moderate or severe malnutrition in the context of acute illness or injury who were given ONS had lower odds of inpatient mortality (moderate OR = 0.72, 95% CI 0.62–0.85; severe OR = 0.76, 95% CI 0.67–0.87; both p < 0.001). Overweight and obese patients who received ONS had higher odds of inpatient mortality (overweight OR = 1.15, 95% CI 1.08–1.22, p < 0.0001; obese OR = 1.08, 95% CI 1.01–1.14, p = 0.02, respectively). For inpatients who were underweight, receiving ONS was protective against inpatient mortality (OR = 0.78, 95% CI 0.68–0.88, p = 0.0001). Thus, among adult inpatients with SARS-CoV-2 infection, malnourished and underweight individuals appeared to experience improved survival when provided with oral nutritional supplements (ONS), whereas overweight or obese patients remain at an elevated risk of mortality. The timing of ONS receipt in hospitalized patients with SARS-CoV-2 influenced mortality. Patients who had earlier time to ONS had 13% lower odds of inpatient mortality (OR = 0.87, 95% CI 0.79–0.97, p = 0.0105). Conclusions: In a cohort of SARS-CoV-2 adult inpatients, those with confirmed malnutrition receiving oral nutrition supplements had a higher likelihood of hospital survival. This is the first study demonstrating an association of oral nutrition intervention with reduced hospital mortality in malnourished SARS-CoV-2-infected adults. Full article

The synthesis and structural characterization of three new triple-stranded helical complexes ([Dy₂(L²)₃]2Cl∙15H₂O (C1), [Y₂(L²)₃]3(NO₃)Cl∙14H₂O∙DMSO (C2), and [Eu₂(L⁴)₃]∙12H₂O (C3), where L² and L⁴ are ligands derived from pyridoxal hydrochloride and succinic or adipic acid dihydrazides, respectively, were described. The X-ray data, combined with spectroscopic measurements, indicated that L² and L⁴ act as bis-tridentate ligands, presenting two tridentate chelating cavities O,N,O to obtain the dinuclear complexes C1–C3. Their antiviral profile was predicted via in silico calculations in terms of interaction with the structural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein in the down- and up-states and complexed with the cellular receptor angiotensin-converting enzyme 2 (ACE2). The best affinity energy values (−9.506, −9.348, and −9.170 kJ/mol for C1, C2, and C3, respectively) were obtained for the inorganic complexes docked in the model spike-ACE2, with C1 being suggested as the most promising candidate for a future in vitro validation. The obtained in silico antiviral trend was supported by the prediction of the electronic and physical–chemical properties of the inorganic complexes via the density functional theory (DFT) approach, representing an original and relevant contribution to the bioinorganic and medicinal chemistry fields. Full article

Background: Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder characterized by bone fragility, most often caused by pathogenic variants in type I collagen genes. In this context, we aimed to describe the clinical and epidemiological characteristics of patients with OI who were hospitalized for coronavirus disease (COVID)-19 in Brazil between 2020 and 2024. Methods: We conducted a retrospective descriptive analysis using data from the Brazilian Unified Health System (SUS, which stands for the Portuguese Sistema Único de Saúde) through the Open-Data-SUS platform. Patients with a confirmed diagnosis of OI and hospitalization due to COVID-19 were included. Descriptive statistical analysis was performed to evaluate demographic, clinical, and outcome-related variables. We included all hospitalized COVID-19 cases with a confirmed diagnosis of OI between 2020 and 2024. Results: Thirteen hospitalized patients with OI and COVID-19 were identified. Most were adults (9; 69.2%), male (7; 53.8%), self-identified as White (9; 69.2%), and all were residents of urban areas (13; 100.0%). The most frequent symptoms were fever (10; 76.9%), cough (9; 69.2%), oxygen desaturation (9; 69.2%), dyspnea (8; 61.5%), and respiratory distress (7; 53.8%). Two patients had heart disease, one had chronic lung disease, and one was obese. As for vaccination status, five patients (38.5%) had been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Four patients (30.8%) required admission to an intensive care unit (ICU), and six (46.2%) required noninvasive ventilatory support. Among those admitted to the ICU, only two required invasive mechanical ventilation. The clinical outcome was death in two cases (15.4%). Both patients were male, White, and had not been vaccinated against SARS-CoV-2. One was 47 years old, was not admitted to the ICU, but required noninvasive ventilation. Despite the underlying condition most patients had favorable outcomes, consistent with an international report. Conclusions: This is the first report to describe the clinical and epidemiological profile of patients with OI hospitalized for COVID-19 in Brazil, providing initial insights into how a rare bone disorder intersects with an acute respiratory infection. The generally favorable outcomes observed—despite the underlying skeletal fragility—suggest that individuals with OI are not necessarily at disproportionate risk of severe COVID-19, particularly when appropriately monitored. The occurrence of deaths only among unvaccinated patients underscores the critical role of SARS-CoV-2 vaccination in this population. Although pharmacological treatment data were unavailable, the potential protective effects of bisphosphonates and vitamin D merit further exploration. These findings support the need for early preventive strategies, systematic vaccination efforts, and dedicated clinical protocols for rare disease populations during infectious disease outbreaks. Full article

Background/Objectives: To investigate the incidence of new-onset diabetic retinopathy (DR) in individuals with pre-existing type 2 diabetes (T2D) up to 3 years post SARS-CoV-2 infection. Methods: This retrospective study consisted of 5151 COVID-19 and 5151 propensity-matched non-COVID-19 patients with T2D in the Montefiore Health System between 1 March 2020 and 17 January 2023. The primary outcome was new-onset DR at least 2 months after the index date up to 17 January 2023. Matching for index date between groups was also used to ensure the same follow-up duration. Hazard ratios (HRs) were computed, adjusted for competing risks. Results: T2D patients with COVID-19 had a higher cumulative incidence of DR than T2D patients. The unadjusted HR for COVID-19 status for developing new DR was 2.44 [1.60, 3.73], p < 0.001. The adjusted HR was 1.70 [1.08, 2.70], p < 0.05, and the adjusted HR for prior insulin use was 3.28 [2.10, 5.12], p < 0.001. Sex, ethnicity, and major comorbidities had no significant association with outcome. Conclusions: T2D patients who contracted COVID-19 exhibited a significantly higher risk of developing DR within three years post infection compared to propensity-matched controls. The increased incidence was primarily driven by greater pre-existing insulin usage and SARS-CoV-2 infection in the COVID-19 positive cohort. Full article