Search Results (4,749)

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

A multilayer linear response model (MLRM) is proposed to generate time-series data based on linear response theory. The proposed MLRM is designed to generate data for anomalous dynamics by extending the conventional single-layer linear response model (SLRM) into multiple layers. While the SLRM is a linear equation with respect to external forces, the MLRM introduces nonlinear interactions, enabling the generation of a wider range of dynamics. The MLRM is applicable to various fields, such as finance, as it does not rely on machine learning techniques and maintains interpretability. We investigated whether the MLRM could generate anomalous dynamics, such as those observed during the coronavirus disease 2019 (COVID-19) pandemic, using pre-pandemic data. Furthermore, an analysis of the log returns and realized volatility derived from the MLRM-generated data demonstrated that both exhibited heavy-tailed characteristics, consistent with empirical observations. These results indicate that the MLRM can effectively reproduce the extreme fluctuations and tail behavior seen during high-volatility periods. Full article

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

Coronavirus disease 2019 (COVID-19) causes cardiovascular complications, which contributes to the high mortality rate of the disease. Emerging evidence indicates that aberrant vascular smooth muscle cell (SMC) function is a key driver of vascular disease in COVID-19. While antivirals alleviate the symptoms of COVID-19, it is not known whether these drugs directly affect SMCs. Accordingly, the present study investigated the ability of three approved COVID-19 antiviral drugs to influence SMC function. Treatment of SMCs with remdesivir (RDV), but not molnupiravir or nirmatrelvir, inhibited cell proliferation, DNA synthesis, and migration without affecting cell viability. RDV also stimulated an increase in heme oxygenase-1 (HO-1) expression that was not observed with molnupiravir or nirmatrelvir. The induction of HO-1 by RDV was abolished by mutating the antioxidant responsive element of the promoter, overexpressing dominant-negative NF-E2-related factor-2 (Nrf2), or treating cells with an antioxidant. Finally, silencing HO-1 partly rescued the proliferative and migratory response of RDV-treated SMCs, and this was reversed by carbon monoxide and bilirubin. In conclusion, the induction of HO-1 via the oxidant-sensitive Nrf2 signaling pathway contributes to the antiproliferative and antimigratory actions of RDV by generating carbon monoxide and bilirubin. These pleiotropic actions of RDV may prevent occlusive vascular disease in COVID-19. 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

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 and Objectives: Coronavirus Disease 2019 (COVID-19) may cause extensive multi-organ pathology, particularly in the lungs, heart, kidneys, and liver. While hypercoagulability—often signaled by elevated D-dimer—has been thoroughly investigated, the concurrent pathological findings across organs and their interrelation with distinct D-dimer levels remain incompletely characterized. This study aimed to evaluate the pathological changes observed in autopsied or deceased COVID-19 patients, focusing on the prevalence of organ-specific lesions, and to perform subgroup analyses based on three D-dimer categories. Methods: We conducted a retrospective review of 69 COVID-19 patients from a Romanian-language dataset, translating all clinical and pathological descriptions into English. Pathological findings (pulmonary microthrombi, bronchopneumonia, myocardial fibrosis, hepatic steatosis, and renal tubular necrosis) were cataloged. Patients were grouped into three categories by admission D-dimer: <500 ng/mL, 500–2000 ng/mL, and ≥2000 ng/mL. Laboratory parameters (C-reactive protein, fibrinogen, and erythrocyte sedimentation rate) and clinical outcomes (intensive care unit [ICU] admission, mechanical ventilation, and mortality) were also recorded. Intergroup comparisons were performed with chi-square tests for categorical data and one-way ANOVA or the Kruskal–Wallis test for continuous data. Results: Marked organ pathology was significantly more frequent in the highest D-dimer group (≥2000 ng/mL). Pulmonary microthrombi and bronchopneumonia increased stepwise across ascending D-dimer strata (p < 0.05). Myocardial and renal lesions similarly showed higher prevalence in patients with elevated D-dimer. Correlation analysis revealed that severe lung and heart pathologies were strongly associated with high inflammatory markers and a greater risk of ICU admission and mortality. Conclusions: Our findings underscore that COVID-19-related organ damage is magnified in patients with significantly elevated D-dimer. By integrating pathology reports with clinical and laboratory data, we highlight the prognostic role of hypercoagulability and systemic inflammation in the pathogenesis of multi-organ complications. Stratifying patients by D-dimer may inform more tailored management strategies, particularly in those at highest risk of severe pathology and adverse clinical outcomes. Full article

Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article

The renin–angiotensin system (RAS) plays a central role in cardiovascular regulation and has gained prominence in the pathogenesis of Coronavirus Disease 2019 (COVID-19) due to the critical function of angiotensin-converting enzyme 2 (ACE2) as the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin IV, but not angiotensin II, has recently been reported to enhance the binding between the viral spike protein and ACE2. To investigate the virological significance of this effect, we developed a single-round infection assay using SARS-CoV-2 viral-like particles expressing the spike protein. Our results demonstrate that while angiotensin II does not affect viral infectivity across concentrations ranging from 40 nM to 400 nM, angiotensin IV enhances viral entry at a low concentration but exhibits dose-dependent inhibition at higher concentrations. These findings highlight the unique dual role of angiotensin IV in modulating SARS-CoV-2 entry. In silico molecular docking simulations indicate that angiotensin IV was predicted to associate with the S1 domain near the receptor-binding domain in the open spike conformation. Given that reported plasma concentrations of angiotensin IV range widely from 17 pM to 81 nM, these levels may be sufficient to promote, rather than inhibit, SARS-CoV-2 infection. This study identifies a novel link between RAS-derived peptides and SARS-CoV-2 infectivity, offering new insights into COVID-19 pathophysiology and informing potential therapeutic strategies. Full article

Introduction: This study aimed to evaluate the diagnostic and prognostic value of soluble intercellular adhesion molecule-1 (sICAM-1) and galectin-3 in patients with type 2 diabetes mellitus (T2D) diagnosed with coronavirus disease 2019 (COVID-19). Participants and Method: This prospective observational study included 45 adult patients (≥18 years) with T2D and confirmed COVID-19 who were followed in the Infectious Diseases and Clinical Microbiology departments between May and June 2022. The control group consisted of 45 healthy volunteers without chronic illness who were presented to the internal medicine outpatient clinic. In addition to routine laboratory biomarkers assessed at hospital admission, the serum levels of sICAM-1 and galectin-3 were measured via ELISA kits. Results: The median age of the patients was 66 years (range: 41–77), and 23 (51.1%) were male. Hypertension was the most common comorbidity in addition to diabetes. Compared with those in the control group, the serum levels of both galectin-3 and sICAM-1 were significantly elevated in patients with COVID-19 and T2D (p < 0.001). However, there was no significant difference in galectin-3 or sICAM-1 levels between survivors and nonsurvivors (p = 0.240 and p = 0.266, respectively). Conclusion: Galectin-3 and sICAM-1 demonstrated stronger diagnostic utility than conventional biomarkers in T2D patients with COVID-19. The elevated levels of these markers may reflect the underlying systemic inflammation observed in diabetic patients with COVID-19. The strong correlation between galectin-3 and sICAM-1 suggests a potential link in their inflammatory regulation, although causality cannot be inferred. Full article

Background: Coronavirus disease 2019 (COVID-19) is frequently complicated by cardiovascular involvement. Soluble growth stimulation-expressed gene 2 (sST2) is a promising cardiovascular biomarker, but its prognostic value in COVID-19 remains unclear. Methods: This retrospective cohort study included 314 hospitalized COVID-19 patients classified into mild/moderate (n = 168) and severe/critical (n = 146). Plasma sST2 were measured using an enzyme-linked immunosorbent assay. Correlation analyses evaluated associations between sST2 and clinical parameters. Cox regression assessed the independent predictive value for cardiovascular events and all-cause mortality. Results: sST2 levels were significantly higher in severe/critical patients (16.877 ng/mL) than in mild/moderate cases (6.189 ng/mL) and healthy controls (4.003 ng/mL). sST2 positively correlated with cardiac injury markers (cTnI, CK-Mb, NT-proBNP), inflammatory indices (IL-1β, hsCRP), D-dimer, and inversely correlated with a left ventricular ejection fraction (r = −0.86). Elevated sST2 independently predicted cardiovascular events (HR = 2.972) and mortality (HR = 4.681). The Kaplan–Meier survival analysis demonstrated higher cardiovascular event rates and lower survival probabilities in patients with elevated sST2. The ROC curve indicated sST2 outperformed cTnI and NT-proBNP in predicting cardiovascular events (AUC = 0.898) and mortality (AUC = 0.871). Conclusion: Elevated sST2 is associated with myocardial injury, inflammation, and poor prognosis in COVID-19, supporting its value for risk stratification. Full article

Coronavirus disease 2019 (COVID-19) produced devastating health and economic impacts worldwide. While progress has been made in vaccine development, effective antiviral treatments remain limited, particularly those targeting the papain-like protease (PLpro) of SARS-CoV-2. PLpro plays a key role in viral replication and immune evasion, making it an attractive yet underexplored target for drug repurposing. In this study, we combined machine learning, molecular dynamics, and molecular docking to identify potential PLpro inhibitors in existing drugs. We performed long-timescale molecular dynamics simulations on PLpro–ligand complexes at two known binding sites, followed by structural clustering to capture representative structures. These were used for molecular docking, including a training set of 127 compounds and a library of 1107 FDA-approved drugs. A random forest model, trained on the docking scores of the representative conformations, yielded 76.4% accuracy via leave-one-out cross-validation. Applying the model to the drug library and filtering results based on prediction confidence and the applicability domain, we identified five drugs as promising candidates for repurposing for COVID-19 treatment. Our findings demonstrate the power of integrating computational modeling with machine learning to accelerate drug repurposing against emerging viral targets. Full article

In recent years, the open data initiative has led to the willingness of many governments, researchers, and organizations to share their data and make it publicly available. Healthcare, disease, and epidemiological data, such as privacy statistics on patients who have suffered from epidemic diseases such as the Coronavirus disease 2019 (COVID-19), are examples of open big data. Therefore, huge volumes of valuable data have been generated and collected at high speed from a wide variety of rich data sources. Analyzing these open big data can be of social benefit. For example, people gain a better understanding of disease by analyzing and mining disease statistics, which can inspire them to participate in disease prevention, detection, control, and combat. Visual representation further improves data understanding and corresponding results for analysis and mining, as a picture is worth a thousand words. In this paper, we present a visual data science solution for the visualization and visual analysis of large sequence data. These ideas are illustrated by the visualization and visual analysis of sequences of real epidemiological data of COVID-19. Through our solution, we enable users to visualize the epidemiological data of COVID-19 over time. It also allows people to visually analyze data and discover relationships between popular features associated with COVID-19 cases. The effectiveness of our visual data science solution in improving the user experience of visualization and visual analysis of large sequence data is demonstrated by the real-life evaluation of these sequenced epidemiological data of COVID-19. Full article

Background: The progressive course of coronavirus disease 2019 (COVID-19) is more frequently observed in individuals with obesity, diabetes, pulmonary and cardiovascular disease, or arterial hypertension. Many patients with these conditions are prescribed statins to treat hypercholesterolaemia. However, statins exhibit additional pleiotropic effects. The present study aims to investigate the effects of all eight currently existing statins on the expression of genes whose products have been reported to be directly associated with complicated COVID-19 disease. Methods: We extended the interpretation of the whole-genome DNA microarray analyses of pancreatic cancer cells MiaPaCa-2 and whole-transcriptome analyses of adipose tissue-derived mesenchymal stem cells AD-MSC that we had performed in the past. From the number of genes with altered expression induced by statins, we focused on those reported to be involved in a complicated course of COVID-19, including APOE and ACE2, genes encoding proteins involved in innate antiviral immunity and respiratory failure genes. Results: Although we did not observe statin-induced changes in the expression of APOE, ACE2 and any of the six genes clustered in the locus associated with respiratory failure in patients with COVID-19, some statins induced changes in the expression of genes encoding their interaction partners. Among genes associated with the immune system, all statins, which are effective in vitro affected the expression of genes encoding IL-6 and IL-8 and interaction partners of NF-kB, which may influence the duration of viral persistence. Conclusions: Statins act on multiple pathways simultaneously, some of which support COVID-19 development, while others suppress it. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is known to affect multiple organ systems, including the respiratory tract and nervous and ocular systems. This retrospective study aimed to characterize the spatiotemporal distribution of viral antigen and associated pathological changes in the nose, lungs, brain, and eyes of K18-hACE2 mice intranasally infected with SARS-CoV-2. Using histology and immunohistochemistry, tissues were examined at 3, 6, and 7/8 days post-infection (dpi). In addition, lung and brain tissues were analyzed by means of RT-qPCR to determine viral RNA titers. Viral antigen was most pronounced in the nose, brain, and lung at 3, 6, and 7/8 dpi, respectively, whereas viral antigen was detected at 6 and 7/8 dpi in the retina. Quantitative PCR confirmed increasing viral RNA levels in both lung and brain, peaking at 7/8 dpi. Nasal and lung inflammation mirrored viral antigen distribution and localization. In the brain, the predominantly basal viral spread correlated with lymphohistiocytic meningoencephalitis, neuronal vacuolation, and altered neurofilament immunoreactivity. Retinal ganglion cells showed viral antigen expression without associated lesions. Microglial activation was evident in both the optic chiasm and the brain. These findings highlight the K18-hACE2 model’s utility for studying extrapulmonary SARS-CoV-2 pathogenesis. Understanding the temporal and spatial dynamics of viral spread enhances insights into SARS-CoV-2 neurotropism and its clinical manifestations. Full article