Search Results (24,587)

Background: Neutralizing antibodies targeting the SARS-CoV-2 Spike protein reduce COVID-19-related risk of hospitalization, particularly in high-risk individuals. The COCOPREV-R study aimed to evaluate and compare clinical outcomes in high-risk SARS-CoV-2 patients treated with dual monoclonal antibody therapies and to identify associated virological factors. Methods: The COCOPREV-R study retrospectively collected real-world data from high-risk patients receiving Bamlanivimab/Etesevimab or Casirivimab/Imdevimab dual monoclonal antibody therapies (22 February 2021 to 15 June 2021). Results: The study included 1004 patients with COVID-19, of whom 691 received Bamlanivimab/Etesevimab and 313 received Casirivimab/Imdevimab. The alpha variant represented 90.1% of those for whom data were available. The risk of hospitalization within 30 days was lower with Bamlanivimab/Etesevimab (12.7%, CI 95% [9.9–16.3%]) compared to Casirivimab/Imdevimab (28.4%, CI 95% [22.7–35.1%) (p < 0.001). The 30-day mortality rates were comparable between both groups (p = 0.982). Analysis of SARS-CoV-2 PCR negativity showed no difference between the two treatment groups (95.2% [93.0–96.9%] and 93.5% [89.1–96.6%] until day 30, p = 0.851 for Bamlanivimab/Etesevimab and Casirivimab/Imdevimab, respectively). Among persistently positive samples with available sequencing results (n = 43), Spike protein changes occurred only in Bamlanivimab/Etesevimab (42.9%) vs. Casirivimab/Imdevimab (0.0%) groups. Q493R (25.0%) and E484K (12.5%) were the most common mutations selected by Bamlanivimab/Etesevimab in follow-up samples. Other factors (immunodepression, comorbidities, and age) did not appear to be associated with the occurrence of Spike protein mutations. Conclusions: A higher rate of hospitalization was seen with Casirivimab/Imdevimab (RONAPREVE^®) in comparison with Bamlanivimab/Etesevimab treatment, but with the emergence of Spike mutations only in the Bamlanivimab/Etesevimab group. Full article

Despite advances in vaccination and therapies for coronavirus disease, challenges remain due to reduced antibody longevity and the emergence of virulent variants like Omicron (BA.1) and its subvariants (BA.1.1, BA.2, BA.3, and BA.5). This study explored the potential of adoptive immunotherapy and harnessing the protective abilities using virus-specific T cells (VSTs). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) VSTs were generated by stimulating donor-derived peripheral blood mononuclear cells with spike, nucleocapsid, and membrane protein peptide mixtures. Phenotypic characterization, including T-cell receptor (TCR) vβ and pentamer analyses, was performed on the ex vivo-expanded cells. We infected human leukocyte antigen (HLA)-partially matched human Calu-3 cells with various authentic SARS-CoV-2 strains in a Biosafety Level 3 facility and co-cultured them with VSTs. VSTs exhibited a diverse TCR vβ repertoire, confirming their ability to target a broad range of SARS-CoV-2 antigens from both the ancestral and mutant strains, including Omicron BA.1 and BA.5. These ex vivo-expanded cells exhibited robust cytotoxicity and low alloreactivity against HLA-partially matched SARS-CoV-2-infected cells. Their cytotoxic effects were consistent across variants, targeting conserved spike and nucleocapsid epitopes. Our findings suggest that third-party partial HLA-matching VSTs could counter immune-escape mechanisms posed by emerging variants of concern. Full article

Sulfur (S) is an essential nutrient for plant growth, influencing not only crop yields but also the composition and function of soil microbial communities. However, the differential effects of S fertilization on abundant and rare taxa in agricultural soils remain poorly understood. This study investigates the impact of different S fertilizer types on maize yield and the structure and stability of soil microbial communities, with a particular focus on abundant and rare taxa. S fertilization led to significant increases maize yield on two typical soils (black soil and sandy soil) (5.3–24.3%) and altered soil properties, including reducing pH (0.04–0.20) and increasing the available sulfur (AS) content (3.8–8.0 mg kg⁻¹), with ammonium sulfate having a more pronounced effect than elemental sulfur. Microbial analysis revealed distinct impacts on the diversity and community structure of both abundant and rare taxa. Elemental sulfur reduced the alpha diversity of abundant taxa more than ammonium sulfate, while NMDS indicated significant shifts in community structures, particularly among abundant taxa. Network analysis showed that S fertilization decreased the complexity of microbial interactions among rare taxa, with ammonium sulfate leading to simpler networks and elemental sulfur resulting in higher modularity. SEM highlighted that the diversity of rare taxa played a crucial role in influencing maize yield, alongside direct effects from soil properties such as AS and SAR (aryl sulfatase). Functional predictions demonstrated that amino acid metabolism and xenobiotic biodegradation and metabolism pathways were enriched in rare taxa, suggesting significant implications for soil health and crop productivity. This study provides new insights into the roles of abundant and rare bacterial taxa under S fertilization, emphasizing their importance in optimizing fertilization strategies for enhanced crop yield in specific soil types. Full article

The completeness of landslide inventories and the selection of evaluation models significantly impact the accuracy of landslide susceptibility assessments. Conventional field geological survey methods and single remote-sensing technology struggle to reliably identify landslides under complex environmental conditions. Moreover, prevalent landslide susceptibility evaluation models are often plagued by issues such as subjectivity and overfitting. Therefore, we investigated the uncertainty in susceptibility modeling from the aspects of landslide inventory quality and model selection. The study focused on Luquan County in Yunnan Province, China. Leveraging multisource remote-sensing technologies, particularly emphasizing optical remote sensing and InSAR time-series deformation detection, the existing historical landslide inventory was refined and updated. This updated inventory was subsequently used to serve as samples. Nine evaluation indicators, encompassing factors such as distance to faults and tributaries, lithology, distance to roads, elevation, slope, terrain undulation, distance to the main streams, and average annual precipitation, were selected on the basis of the collation and organization of regional geological data. The information value and two coupled machine-learning models were formulated to evaluate landslide susceptibility. The evaluation results indicate that the two coupled models are more appropriate for susceptibility modeling than the single information value (IV) model, with the random forest model optimized by genetic algorithm in Group I2 exhibiting higher predictive accuracy (AUC = 0.796). Furthermore, comparative evaluation results reveal that, under equivalent model conditions, the incorporation of a remote-sensing landslide inventory significantly enhances the accuracy of landslide susceptibility assessment results. This study not only investigates the impact of landslide inventories and models on susceptibility outcomes but also validates the feasibility and scientific validity of employing multisource remote-sensing technologies in landslide susceptibility assessment. Full article

Some respiratory viruses, such as Human Rhinovirus, SARS-CoV-2, and Enterovirus D-68 (EV-D68), share the feature of hijacking host lipids in order to generate specialised replication organelles (ROs) with unique lipid compositions to enable viral replication. We have recently uncovered a novel non-canonical function of the stimulator of interferon genes (STING) pathway, as a critical factor in the formation of ROs in response to HRV infection. The STING pathway is the main DNA virus sensing system of the innate immune system controlling the type I IFN machinery. Although it is well-characterised as part of the DNA sensor machinery, the STING function in RNA viral infections is largely unexplored. In the current study, we investigated whether other RO-forming RNA viruses, such as EV-D68 and SARS-CoV-2, can also utilise STING for their replication. Using genetic and pharmacological inhibition, we demonstrate that STING is hijacked by these viruses and is utilised as part of the viral replication machinery. STING also co-localises with glycolytic enzymes needed to fuel the energy for replication. The inhibition of STING leads to the modulation of glucose metabolism in EV-D68-infected cells, suggesting that it might also manipulate immunometabolism. Therefore, for RO-generating RNA viruses, STING seems to have non-canonical functions in membrane lipid re-modelling, and the formation of replication vesicles, as well as immunometabolism. Full article

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 2019 (COVID-19), a disease with very heterogeneous symptoms. Dyslipidaemia is prevalent in at least 20% of Europeans, and dyslipidaemia before SARS-CoV-2 infection increases the risk for severe COVID-19 and mortality by 139%. Many reports described reduced serum cholesterol levels in virus-infected patients, in particular in those with severe disease. The liver is the major organ for lipid homeostasis and hepatic dysfunction appears to occur in one in five patients infected with SARS-CoV-2. Thus, SARS-CoV-2 infection, COVID-19 disease severity and liver injury may be related to impaired cholesterol homeostasis. These observations prompted efforts to assess the therapeutic opportunities of cholesterol-lowering medications to reduce COVID-19 severity. The majority of studies implicate statins to have beneficial effects on disease severity and outcome in COVID-19. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies have also shown potential to protect against COVID-19. This review describes the relationship between systemic cholesterol levels, liver injury and COVID-19 disease severity. The potential effects of statins and PCSK9 in COVID-19 are summarised. Finally, the relationship between cholesterol and lung function, the first organ to be affected by SARS-CoV-2, is described. Full article

Monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy, offering unprecedented specificity and diverse mechanisms to combat malignant cells. These biologic agents have emerged as a cornerstone in targeted cancer treatment, binding to specific antigens on cancer cells and exerting their therapeutic effects through various mechanisms, including inhibition of signaling pathways, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). The unique ability of mAbs to engage the immune system and directly interfere with cancer cell function has significantly enhanced the therapeutic armamentarium against a broad spectrum of malignancies. mAbs were initially studied in oncology; however, today, treatments have been developed for eye diseases. This review discusses the current applications of mAbs for the treatment of ocular diseases, discussing the specificity and the variety of mechanisms by which these molecules exhibit their therapeutic effects. The benefits, drawbacks, effectiveness, and risks associated with using mAbs in ophthalmology are highlighted, focusing on the most relevant ocular diseases and mAbs currently in use. Technological advances have led to in vitro production methods and recombinant engineering techniques, allowing the development of chimeric, humanized, and fully human mAbs. Nowadays, many humanized mAbs have several applications, e.g., for the treatment of age-related macular disease, diabetic retinopathy, and uveitis, while studies about new applications of mAbs, such as for SARS-CoV-2 infection, are also currently ongoing to seek more efficient and safe approaches to treat this new ocular disease. Full article

In a time of climate change, population growth, and globalization, the risk of viral spread has significantly increased. The 21st century has already witnessed outbreaks of Severe Acute Respiratory Syndrome virus (SARS-CoV), Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2), Ebola virus and Influenza virus, among others. Viruses rapidly adapt and evade human immune systems, complicating the development of effective antiviral countermeasures. Consequently, the need for novel antivirals resilient to viral mutations is urgent. In this study, we developed a CRISPR-Cas13b system to target SARS-CoV-2. Interestingly, this system was also efficient against SARS-CoV, demonstrating broad-spectrum potential. Our findings highlight CRISPR-Cas13b as a promising tool for antiviral therapeutics, underscoring its potential in RNA-virus-associated pandemic responses. Full article

Combining various viewpoints to produce coherent and cohesive results requires decision fusion. These methodologies are essential for synthesizing data from multiple sensors in remote sensing classification in order to make conclusive decisions. Using fully polarimetric Synthetic Aperture Radar (PolSAR) imagery, our study combines the benefits of both approaches for detection by extracting Pauli’s and Krogager’s decomposition components. The Local Pattern Differences (LPD) method was employed on every decomposition component for pixel-level texture feature extraction. These extracted features were utilized to train three independent classifiers. Ultimately, these findings were handled as independent decisions for each land cover type and were fused together using a decision fusion rule to produce complete and enhanced classification results. As part of our approach, after a thorough examination, the most appropriate classifiers and decision rules were exploited, as well as the mathematical foundations required for effective decision fusion. Incorporating qualitative and quantitative information into the decision fusion process ensures robust and reliable classification results. The innovation of our approach lies in the dual use of decomposition methods and the application of a simple but effective decision fusion strategy. Full article

This study elaborates on a typology of demographic change and tests this definition at the lowest granular level (LAU2, municipality) with official data. This typology distinguishes between fragile and resilient municipalities based on population dynamics (in terms of duration and intensity) over 1991–2021. This study’s second aim is to elaborate a spatial autoregressive econometric model to evaluate to what extent and in which direction the rate of participation of potential beneficiaries of the Rural Development Programmes (RDPs) of 2014–2020 is affected by demographic change and other explanatory variables. Regression models compare the results of the OLS (aspatial) and spatial autoregressive models (SAR) of four types of participation rates (all RDP schemes; all LEADER schemes; sectoral schemes of RDP and LEADER; non-sectoral schemes of RDPs and LEADER). This comparison makes it possible to understand the differences between centralised and decentralised management and between sectoral and broader rural-targeted schemes. The results of the models appear attractive in interpreting the role of RDP instruments in different regions and local areas. First, the rate of participation is strongly dependent on macro-regional differences. Regarding the demographic factors at the local level, this study highlights that demographic fragility does not necessarily hamper the use of RDP measures. Conversely, the participation rate in RDP policy schemes seems particularly significant in very fragile areas, whereas significance has yet to be proved in other demographic typologies. This result holds particularly true for the policy uptake of non-sectoral schemes. Furthermore, LEADER decentralised interventions fit the fragile areas more than resilient and vital ones due to the territorially targeted approach followed by the Local Action Groups. Full article

Objectives: The purpose of this study was to compare and contrast Kawasaki disease (KD) with multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. Methods: A retrospective analysis of the medical records of patients diagnosed with KD and MIS-C at a single institution from July 2020 to November 2021 was performed. Results: The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. The MIS-C patients were older (p < 0.001) and had prolonged hospitalizations (p = 0.023), elevated neutrophil counts (p < 0.001), C-reactive protein (p < 0.001), procalcitonin (p < 0.001), interleukin-6 (p < 0.014), ferritin (p < 0.001), fibrinogen (p < 0.001), troponin I (p = 0.001), NT-proBNP (p < 0.001), and D-dimer levels (p < 0.001). There were more cases of hypotension (p = 0.024), decreased left ventricular function (p = 0.023), and a greater need for corticosteroids (p < 0.001), enoxaparin (p = 0.045), and therapeutic plasma exchange (p < 0.001). Kawasaki disease patients had a greater incidence of rash (p < 0.001), changes in oral mucosa (p < 0.001), conjunctival injection (p < 0.001), extremity changes (p < 0.001), and cervical lymphadenopathy (p < 0.001). They had a longer duration of fever (p < 0.001), elevated white blood cell count (p < 0.001), platelet count (p < 0.001), and alanine aminotransferase level (p < 0.001). The two groups were similar regarding the hemoglobin levels, erythrocyte sedimentation rates, albumin levels, and the frequency of coronary aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Conclusions: Advanced patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas prolonged fever and classical clinical features of KD favor KD. Full article

The emergence of COronaVIrus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presented a global health challenge since its identification in December 2019. With clinical manifestations ranging from mild respiratory symptoms to severe multi-organ dysfunction, COVID-19 continues to affect populations worldwide. The complex interactions between SARS-CoV-2 variants and the human immune system are crucial for developing effective therapies, vaccines, and preventive measures. Understanding these immune responses highlights the intricate nature of COVID-19 pathogenesis. This retrospective study analyzed, by flow cytometry approach, a cohort of patients infected with SARS-CoV-2 during the initial pandemic waves from 2020 to 2021. It focused on untreated individuals at the time of hospital admission and examined the presence of T_R3-56 cells in their immune profiles during the anti-viral immune response. Our findings provide additional insights into the complex immunological dynamics of SARS-CoV-2 infection and highlight the potential role of T_R3-56 cells as crucial components of the immune response. We suggest that T_R3-56 cells could serve as valuable biomarkers for identifying more severe cases of COVID-19, aiding in the assessment and management of the disease. Full article

Background: In 2019, a new coronavirus disease emerged in Wuhan, China, known as SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, and caused an ongoing pandemic. Symptomatology of the syndrome is variable, with complications extending to hematopoiesis and hemostasis. Approximately a year after onset of the virus, four vaccination formulas became available to the public, based on a viral vector or mRNA technology. These vaccine formulas have been hampered with hematological complications, like vaccine-induced immune thrombotic thrombocytopenia (VITT) and vaccine-related ITP (immune thrombocytopenic purpura). ITP is a disease with autoimmune pathogenesis characterized by antibody production against platelets and an increased hemorrhagic risk. A decent number of cases have been referred to as possible adverse effects of COVID-19 vaccinations. Case presentation: in this case report, we present two cases of newly diagnosed ITP after vaccination with ChAdOx1-S (AstraZeneca), with a good response to treatment with thrombopoietin-receptor agonists (TPO-RAs). Discussion: we observed an absence of response after corticosteroids and IVIG therapy and a positive therapeutic outcome on TPO-RA. Conclusions: in the ongoing pandemic, there is an urgent need to create therapeutic guidelines for vaccination-related clinical entities and to clarify indications for the vaccination of patients with pre-existing hematological diseases. Full article

This study in Singapore analysed the incubation periods of the following SARS-CoV-2 variants: Wuhan-Hu-1, Delta, and Omicron. Three pandemic waves were examined: Wuhan-Hu-1 (January 2020–March 2021), Delta (May–October 2021), and Omicron (January–June 2022). Data from the SingHealth COVID-19 registry, covering patients from 23 January 2020 to 10 June 2022, were used to calculate incubation periods during the three time periods. The study found median incubation periods of 11 days for Wuhan-Hu-1, 3 days for Delta, and 3 days for Omicron (p-value: <0.001). This study highlighted the impact of different containment measures and the importance of robust EMR systems for tracking and managing infectious diseases. Key challenges included accurate contact tracing and IT infrastructure capabilities. The findings support the use of EMR data for future infectious disease preparedness in Singapore. Full article

Background. The emergence, global spread, and persistence of SARS-CoV-2 resulted in an unprecedented need for effective antiviral drugs. Throughout the pandemic, various drug development and treatment strategies were adopted, including repurposing of antivirals designed for other viruses along with a multitude of other drugs with varying mechanisms of action (MoAs). Furthermore, multidrug treatment against COVID-19 is an ongoing topic and merits further investigation. Method/Objectives. We assessed the efficacy of multidrug treatment against SARS-CoV-2 in reconstituted human nasal epithelia, using combinations of molnupiravir and nirmatrelvir as a baseline, adding suboptimal concentrations of either GS-441524 or ivermectin, attempting to increase overall antiviral activity while lowering the overall therapeutic dose. Results. Nirmatrelvir combined with molnupiravir, GS-441524, or ivermectin at suboptimal concentrations show increased antiviral activity compared to single treatment. No triple combinations showed improved inhibition of SARS-CoV-2 replication beyond what was observed for double treatments. Conclusions. In general, we observed that the addition of a third compound is not beneficial for antiviral activity, while various double combinations exhibit increased antiviral activity over single treatment. Full article