Search Results (241)

The association between COVID-19 vaccination and thromboembolic events has garnered significant research attention, particularly with the advent of vaccines based on adenoviral vectors, including AstraZeneca’s and Johnson & Johnson’s vaccines. This review underscores the uncommon occurrence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and vaccine-induced thrombotic thrombocytopenia (VITT) following COVID-19 vaccination. Although these complications are extremely rare compared to the heightened risk of thrombosis from COVID-19 infection, elements like age, biological sex, type of vaccine and underlying health conditions may contribute to their development. In addition, rare renal complications such as acute kidney injury and thrombotic microangiopathy have been documented, broadening the spectrum of potential vaccine-associated thrombotic manifestations. Current guidelines emphasize early detection, individualized risk assessment, and use of anticoagulation therapy to mitigate risks. Despite these events, the overwhelming majority of evidence supports the continued use of COVID-19 vaccines, given their proven efficacy in reducing severe illness and mortality. In addition, recent comparative data confirm that mRNA-based vaccines are associated with a significantly lower risk of serious thrombotic events compared to adenoviral vector platforms. Ongoing research is essential to further refine preventive and therapeutic strategies, particularly for at-risk populations. Full article

The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 variants. This review aimed to evaluate the factors influencing the immunogenicity and effectiveness of COVID-19 vaccines to inform future vaccine advancement strategies. A narrative review with systematic approach was conducted following PRISMA guidelines for narrative review. Literature was sourced from databases including PubMed, Embase, and Web of Science for studies published between December 2019 and May 2025. Encompassed studies assessed vaccine efficacy, immunogenicity, and safety across various populations and vaccine platforms. Data were collected qualitatively, with quantitative data from reviews highlighted where available. We have uncovered a decline in vaccine efficacy over time and weakened protection against novel variants such as Delta and Omicron. Booster doses, specifically heterologous regimens, improved immunogenicity and increased protection. Vaccine-induced neutralizing antibody titers have been found to correlate with clinical protection, although the long-term correlates of immunity remain poorly defined. The induction of IgG4 antibodies after repeated mRNA vaccinations raised concerns about potential modulation of the immune response. COVID-19 vaccines have contributed significantly to pandemic control; however, their efficacy is limited by the evolution of the virus and declining immunity. Forthcoming vaccine strategies should focus on broad-spectrum, variant-adapted formulations and defining robust comparisons of protection. Recognizing the immunological basis of vaccine response, including the role of specific antibody subclasses, is fundamental for optimizing long-term protection. Full article

Despite the prevalence of fucosylated IgG in plasma, specific IgGs with low core fucosylation sporadically emerge in response to virus infections and blood cell alloantigens. This low fucosylation of IgG is implicated in the pathogenesis of SARS-CoV-2 and dengue infections. In COVID-19, the presence of IgGs with low core fucosylation (afucosylated IgGs) targeting spike protein predicts disease progression to a severe form and actively mediates this progression. This study reveals that SARS-CoV-2 infection of megakaryocytes promotes the generation of pathogenic afucosylated anti-spike IgGs, leading to outcomes, such as pulmonary vascular thrombosis, acute lung injury, and mortality in FcγRIIa-transgenic mice. Platelets from mice injected with virus-infected human megakaryocytes express significant activation biomarkers, indicating a direct link between the immune response and platelet activation. Mice injected with virus-infected human megakaryocytes demonstrate an elevated rate of thrombus formation induced by FeCl₃ (4%) and a reduction in bleeding time, emphasizing the intricate interplay of viral infection, immune response, and hemostatic complications. Treatment with inhibitors targeting FcγRIIa, serotonin, or complement anaphylatoxins of mice injected with spike-expressing MKs successfully prevents observed platelet activation, thrombus formation, and bleeding abnormalities, offering potential therapeutic strategies for managing severe outcomes associated with afucosylated IgGs in COVID-19 and related disorders. Full article

Background/Objectives: Non-pancreatic hyperlipasemia (NPHL) is associated with high in-hospital mortality, with sepsis being one of the most common etiologies. The prognostic value of hematological parameter-derived inflammatory scores has not been extensively studied in NPHL to date. Methods: The prognostic value of eight inflammatory scores for in-hospital mortality was assessed in a total of 545 NPHL patients from two hospitalized patient cohorts (COVID-19 [n = 144] and non-COVID-19 [n = 401], the latter stratified as bacterial sepsis [n = 111] and absence of systemic infection [n = 290]). We assessed the neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), neutrophil-to-lymphocyte and platelet ratio (N/(LP)), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), aggregate index of systemic inflammation (AISI), systemic inflammation index (SII), and systemic inflammation response index (SIRI), comparing their prognostic value among etiological groups. Results: Patients with bacterial sepsis were older, had more comorbidities, and experienced worse outcomes, including longer hospitalization (median: 15, 7, and 11 days; p < 0.001), higher ICU admission rates (75.7%, 33.8%, and 47.9%, p < 0.001), and increased mortality (45.0%, 13.8%, and 38.2%, p < 0.001), compared to those without systemic infection or with COVID-19-induced NPHL. Overall, NLR, dNLR, and N/(LP) were the most accurate predictors of in-hospital mortality at admission (AUROC: non-infection: 0.747; 0.737; 0.772; COVID-19: 0.810; 0.789; 0.773, respectively). The accuracy of NLR decreased in bacterial sepsis, and only N/(LP) and PLR remained associated with in-hospital mortality (AUROC: 0.653 and 0.616, respectively). Conclusions: The prognostic performance of hematological parameter-derived inflammatory scores in NPHL is etiology-dependent. NLR is the most accurate prognostic tool for mortality in the absence of bacterial sepsis, while N/(LP) is the best score in sepsis-induced NPHL. Full article

The COVID-19 pandemic has significantly impacted global health, with pulmonary embolism (PE) emerging as a critical complication due to the hypercoagulable state induced by SARS-CoV-2 infection. Despite advancements in prevention and treatment, PE remains a major cause of morbidity and mortality in COVID-19 patients. This study analyzes the trends, outcomes, and contributing factors of PE across ten pandemic waves in Romania, highlighting the evolving clinical burden and management approaches. This retrospective observational study was conducted on confirmed COVID-19 patients that also developed PE, who were admitted to “Victor Babeș” Hospital and Municipal Emergency Hospital in Timișoara, Romania. Data on demographics, clinical features, inflammatory markers, comorbidities, and treatment were collected from medical records. Statistical analyses, including ANOVA and Kaplan–Meier survival analysis, were conducted to evaluate trends and survival outcomes over time. The study included 166 patients, with a mean age of 67.26 ± 13.57 years. Mortality peaked at 50% in Wave 1, declined to 12% in Wave 7, and increased again to 28% in Wave 10. Intubation rates varied, with a high of 29% in Wave 6 and a low of 12% in Wave 8. Lung involvement was the most severe in Wave 4 (mean 0.54 ± 0.18) but improved in later waves, reaching a mean of 0.24 ± 0.12 in Wave 8. This study highlights the dynamic trends in PE during the COVID-19 pandemic in Romania. Improved clinical management, vaccination, and adaptive healthcare strategies contributed to better outcomes in later waves. Full article

The lung microbiota is integral to maintaining microenvironmental homeostasis, influencing immune regulation, host defense against pathogens, and overall respiratory health. The dynamic interplay among the lung microbiota emphasizes their significance in shaping the respiratory milieu and potential impact on diverse pulmonary affections. This investigation aimed to identify the effects of invasive mechanical ventilation on the lung microbiome. Materials and Methods: A systematic review was conducted with registration number CRD42023461618, based on a search of PubMed, SCOPUS, and Web of Science databases, in line with the PRISMA guidelines. To achieve this, “(mechanical ventilation) AND (microbiota)” was used as the search term, replicable across all databases. The closing date of the search was 12 March 2025, and the evidence was scored using the MINORS scale. Results: A total of 16 studies were included, with patients aged 13.6 months to 76 years, predominantly male (64.2%). Common ICU admission diagnoses requiring invasive mechanical ventilation (IMV) included pneumonia, acute respiratory failure, and COVID-19. IMV was associated with reduced lung microbiota diversity and an increased prevalence of pathogenic bacteria, including Prevotella, Streptococcus, Staphylococcus, Pseudomonas, and Acinetobacter. The most frequently used antibiotics were cephalosporins, aminoglycosides, and penicillins. IMV-induced pulmonary dysbiosis correlated with higher infection risk and mortality, particularly in pneumonia and COVID-19 cases. Factors such as antimicrobial therapy, enteral nutrition, and systemic inflammation contributed to these alterations. Conclusions: Invasive mechanical ventilation has been associated with the development of alterations in the respiratory microbiome, resulting in reduced diversity of lung microorganisms. Full article

Since the onset of the COVID-19 pandemic, Japan has experienced a significant rise in mortality, with excess deaths surpassing historical projections. Statistical data indicate a sharp increase in mortality rates from 2021 onward, attributed to COVID-19, aging demographics, cardiovascular diseases, and malignancies. Preliminary 2024 data suggest continued excess mortality, fueling public debate. This review analyzes national and municipal mortality trends using official Japanese statistics and comparative data from South Korea, the U.S., and the EU. Findings reveal a sharp mortality rise post-2021 in Japan and South Korea, while Western nations experienced peak deaths in 2020, followed by declines. The review explores contributing factors, including potential vaccine-related adverse effects, declining healthcare access, pandemic-induced stress, and demographic shifts. Notably, older adults’ reluctance to seek medical care led to delayed diagnoses, treatment interruptions, and preventable deaths. Although some argue that declining COVID-19 vaccination rates in 2023 may have contributed to rising mortality in 2024, available data suggest a multifactorial causation. Japan’s rapidly aging population, coupled with increasing mortality and declining birth rates, presents profound social and economic challenges. A nuanced approach, avoiding simplistic causal claims, is crucial for understanding these trends. This review highlights the need for a sustainable societal framework to address demographic shifts and improve healthcare resilience. Future pandemic strategies must balance infection control measures with mitigating unintended health consequences to ensure a more adaptive and effective public health response. Full article

Robust credit risk prediction in emerging economies increasingly demands the integration of external factors (EFs) beyond borrowers’ control. This study introduces a scenario-based methodology to incorporate EF—namely COVID-19 severity (mortality and confirmed cases), climate anomalies (temperature deviations, weather-induced road blockages), and social unrest—into machine learning (ML) models for credit delinquency prediction. The approach is grounded in a CRISP-DM framework, combining stationarity testing (Dickey–Fuller), causality analysis (Granger), and post hoc explainability (SHAP, LIME), along with performance evaluation via AUC, ACC, KS, and F1 metrics. The empirical analysis uses nearly 8.2 million records compiled from multiple sources, including 367,000 credit operations granted to individuals and microbusiness owners by a regulated Peruvian financial institution (FMOD) between January 2020 and September 2023. These data also include time series of delinquency by economic activity, external factor indicators (e.g., mortality, climate disruptions, and protest events), and their dynamic interactions assessed through Granger causality to evaluate both the intensity and propagation of external shocks. The results confirm that EF inclusion significantly enhances model performance and robustness. Time-lagged mortality (COVID MOV) emerges as the most powerful single predictor of delinquency, while compound crises (climate and unrest) further intensify default risk—particularly in portfolios without public support. Among the evaluated models, CNN and XGB consistently demonstrate superior adaptability, defined as their ability to maintain strong predictive performance across diverse stress scenarios—including pandemic, climate, and unrest contexts—and to dynamically adjust to varying input distributions and portfolio conditions. Post hoc analyses reveal that EF effects dynamically interact with borrower income, indebtedness, and behavioral traits. This study provides a scalable, explainable framework for integrating systemic shocks into credit risk modeling. The findings contribute to more informed, adaptive, and transparent lending decisions in volatile economic contexts, relevant to financial institutions, regulators, and risk practitioners in emerging markets. Full article

The COVID-19 pandemic, caused by SARS-CoV-2, has significantly affected global health, with severe inflammatory responses leading to tissue damage and persistent symptoms. Macrophage-derived extracellular vesicles (EVs) are involved in the modulation of immune responses, but their involvement in SARS-CoV-2-induced inflammation and senescence remains unclear. Triggering receptors expressed on myeloid cell-1 (TREM-1) are myeloid cell receptors that amplify inflammation, described as a biomarker of the severity and mortality of COVID-19. This study investigated the composition and effects of macrophage-derived EVs stimulated by SARS-CoV-2 (MφV-EVs) on the recipient cell response. Our results, for the first time, show that SARS-CoV-2 stimulation modifies the cargo profile of MφV-EVs, enriching them with TREM-1 and miRNA-155 association, along with MMP-9 and IL-8/CXCL8. These EVs carry senescence-associated secretory phenotype (SASP) components, promote cellular senescence, and compromise antibacterial defenses upon internalization. Our findings provide evidence that MφV-EVs are key drivers of inflammation and immune dysfunction, underscoring their potential as therapeutic targets in COVID-19. Full article

The implementation of COVID-19 policy and the rapid development of SARS-CoV-2 vaccines in the early pandemic significantly contained numerous outbreaks and reduced the severity and mortality of COVID-19. However, the population immunity induced by existing vaccines was insufficient to prevent SARS-CoV-2 outbreaks. The host immunity induced by the wide spread of Omicron variants and its influence on emerging SARS-CoV-2 variants are attracting broad attention. In this study, a clinical data analysis of the patients indicated that pre-vaccination reduced inflammatory responses and mitigated the severity of COVID-19 cases caused by natural infection with Omicron BA.5.2. The analysis of adaptive immune responses indicated that natural infection with BA.5.2 induced robust and broad immune responses, including both humoral and T cell-mediated immune responses (IFN-γ) against highly conserved viral antigens, and provided cross-reactive neutralization against various viral variants. Collectively, we report that the natural infection with Omicron BA.5.2 induced broad cross-reactive immunity against SARS-CoV-2 variants, which suggests that the development of a live attenuated SARS-CoV-2 vaccine with desired safety, high efficacy, broad spectrum, and long-term immune persistence is feasible. Therefore, we suggest that herd immunity, achieved through vaccination with attenuated vaccines, combined with booster doses of existing vaccines and antiviral therapy for people with high viral loads, may contribute to the eradication of this virus. Full article

Sepsis is a leading cause of mortality in critically ill patients, arising from a dysregulated immune response to infection. While traditionally associated with bacterial pathogens, severe COVID-19 can induce a sepsis-like syndrome, characterized by systemic inflammation, endothelial dysfunction, and coagulation abnormalities. This study aimed to assess the prognostic value of age, inflammatory markers, coagulation dysfunction, comorbidity burden, and lung involvement on computer tomography (CT) scans in predicting poor outcomes. We conducted a prospective cohort study including 163 patients diagnosed with COVID-19-related sepsis. Univariate and multivariable logistic regression analyses were performed to identify the independent predictors of unfavorable outcomes. Higher D-dimer (OR: 1.417, p = 0.020) and C-reactive protein (CRP) levels (OR: 1.010, p = 0.027) were independently associated with poor outcomes. A greater than 50% lung involvement on CT (OR: 1.774, p = 0.025) was also a significant predictor. The Charleson Comorbidity Index (CCI) showed a strong trend toward significance (p = 0.065), while age lost statistical significance after adjusting for comorbidities. Our findings suggest that D-dimers, CRP, and lung involvement on CT are key independent predictors of poor outcomes in COVID-19-related sepsis. These results emphasize the importance of inflammatory and coagulation markers, alongside comorbidity burden, in early risk assessment. Further prospective studies are warranted to refine predictive models for severe COVID-19 cases complicated by sepsis. Full article

Most studies analyzing data from patients who experienced at least one episode of acute COVID-19 infection have attributed the cascade of immediate and late complications to disruption of the inflammatory system and neutrophil activity in particular. Among the various functions of neutrophils is the release of pro-inflammatory mediators, including interleukin-6 (IL-6). Oxidative stress induced by pro-inflammatory mediators secreted by neutrophils leads to vascular endothelial dysfunction. Neutrophil counts and the neutrophil-to-lymphocyte ratio (NLR) are directly associated with COVID-19 patient survival, with higher values correlating with increased mortality. To assess endothelial dysfunction secondary to COVID-19 infection, we conducted a retrospective study involving two patient cohorts, each comprising 99 participants: one group with a history of COVID-19 infection and another without. The study aimed to demonstrate the presence of endothelial dysfunction in patients with moderate COVID-19 infection using flow-mediated dilatation (FMD) of the brachial artery and to evaluate its correlation with key inflammatory markers (erythrocyte sedimentation rate—ESR, fibrinogen, NLR, IL-6). FMD values were significantly reduced (p < 0.0001) in post-COVID-19 patients compared to those without prior infection. ESR (p < 0.0001), fibrinogen (p < 0.0001), C-reactive protein (CRP) (p < 0.0001), leukocyte count (p < 0.0001), and granulocyte count (p < 0.0001) were inversely correlated with FMD values. Among post-COVID-19 patients, all analyzed parameters demonstrated a statistically significant impact on FMD, with ESR showing the strongest effect, accounting for nearly 63% of the dependency. ANOVA testing confirmed an inverse association between NLR quartiles and FMD, as well as between IL-6 levels and FMD. In conclusion, this study highlights the presence of endothelial dysfunction in post-COVID-19 patients, as assessed by FMD, and demonstrates statistically significant inverse correlations between FMD values, IL-6 levels, and the neutrophil-to-lymphocyte ratio. Full article

Background: Rabies is a preventable zoonotic disease caused by the rabies virus (RABV) with a high mortality rate. Most vaccines on the market or under development have issues, such as low single-dose neutralization titer, complex processes, and high costs. During the COVID-19 pandemic, the successful development of mRNA vaccines opened up a new avenue for preventive vaccines. As a new technology, mRNA has higher scalability. Methods: In this study, we designed an mRNA encoding the RV-G protein, encapsulated by our own muscle-targeting lipid nanoparticles (LNPs), and evaluated the expression of the RV-G protein in vitro, its immunogenicity, and its protection against virus infection in vivo. Results: The results show that RV-G mRNA was significantly expressed in vitro. High Virus-IgG binding titers and virus-neutralizing antibody titers (VNT) were induced by immunization with RV-G mRNA-LNP. Additionally, our results showed that the RV-G mRNA vaccine is better than commercially available vaccines in mice. Conclusions: Our research highlights the potential of the mRNA-LNP platform in developing next-generation rabies vaccines. Full article

Five years into the COVID-19 pandemic, the availability of effective vaccines has substantially reduced new cases, hospitalizations, and mortality. However, the waning of immunity has been a topic of particular interest in relation to disease control. The objective of this study is to investigate the impact of the decline in vaccine-induced immunity (${\omega }_1$) and infection-acquired immunity (${\omega }_2$) on disease dynamics. For this purpose, we use a compartmental model with seven compartments that accounts for differential morbidity, vaccination, and waning immunity. A compartmental model divides a population into distinct groups depending on their disease status. The temporal changes in the compartments are represented through ordinary differential equations (ODEs). The model is mathematically analyzed to show that a backward bifurcation (i.e., a perverse outcome) may occur when the vaccinated reproduction number (${\mathcal{R}}_v$) is equal to unity. Both local and global sensitivity analysis on the reproduction number reveal that the vaccine efficacy, waning of vaccine-induced immunity, vaccine coverage rate, coefficients of transmissibility, and the recovery rate for mild infections are the most sensitive parameters. The global sensitivity analysis on the cumulative number of infections shows that ${\omega }_1$ and ${\omega }_2$ are both pivotal parameters, while ${\omega }_2$ has a higher influence. Simulations on infections and mortality suggest that the changes in ${\omega }_2$ result in dynamics that are more pronounced compared to the dynamics resulting from the changes in ${\omega }_1$, thus indicating the importance of the duration of infection-acquired immunity in disease spread. Full article

Background: Infections pose a significant risk of morbidity and mortality to patients on biologics, with the vaccination of both patients and their close contacts serving as a key preventive measure. Despite its importance, there are limited data on the vaccination coverage for this group, and no studies have examined the vaccination status of patients’ close contacts. Objectives: To assess vaccination rates among patients on biologics and their household contacts, identifying reasons for inadequate vaccination and examining factors influencing vaccination status and attitudes is crucial. Methods: A cross-sectional study was conducted from September 2022 to February 2023 at the two hospitals in Heraklion, Crete, including adult and pediatric patients on biologics. Data were collected through medical records and interviews and analyzed using Microsoft Excel 2016 and MedCalc2006. Results: Among the 446 adults, vaccination rates were as follows: 83% for COVID-19, 73.8% for influenza, 64.5% for the pneumococcal conjugate vaccine, 29.6% for the pneumococcal polysaccharide vaccine, and 4% for Tdap. Among the 26 children included, those with basic immunization schedule coverage exceeded 96%, but rates for the vaccines usually administered at adolescence were lower (Tdap: 47.8%, HPV: 42.1%, MenACWY: 66.7%). COVID-19 vaccination was at 38.5%. Regarding the additional vaccines recommended due to treatment-induced immunosuppression, 69.2% of pediatric patients received the annual influenza vaccine, while only 19.2% received the pneumococcal polysaccharide vaccine. Household contacts demonstrated low vaccination rates (<59%), except for COVID-19 (81%). Female gender (p < 0.007) and older age (by 1 year, p < 0.001) were associated with favorable attitudes and higher coverage in adults, while in pediatric patients, no statistically significant associations were found. A lack of physician recommendation was the primary reported reason for not being vaccinated. Conclusions: Significant vaccination gaps exist among patients on biologics and their close contacts, largely due to inadequate physician recommendations. Raising awareness and strengthening healthcare provider roles are essential to improve coverage in this high-risk group. Full article