Search Results (9,764)

Objective: Homeless individuals are vulnerable, and a high burden of mental health problems is suspected. We aim to identify the prevalence and key predictors of probable depression and anxiety among homeless individuals in Germany during the Coronavirus disease-2019 (COVID-19) pandemic. Study Design: Nationwide multicentre cross-sectional study including clinical, laboratory, and questionnaire-based data on the health of homeless individuals in Germany. Methods: Data were used from the National Survey on the psychiatric and somatic health of homeless individuals during the COVID-19 pandemic. Probable depression and anxiety were determined using the Patient Health Questionnaire 9 and the General Anxiety Disorder 2 questionnaire. Logistic regression analysis was used to identify key predictors of probable depression and anxiety. Results: A high prevalence of probable depression (26.8% [95% CI: 23.2–30.3]) and anxiety (27.2% [95% CI: 23.7–30.7]) was found. Logistic regressions showed both probable depression and anxiety associated with being female (depression: OR 1.80 [95% CI: 1.06–3.03]; anxiety: OR: 1.69 [95% CI: 1.03–2.76]), daily use of any illegal substances (depression: OR 3.20 [95% CI: 1.87–5.49]; anxiety: OR 2.04 [95% CI: 1.21–3.45]), and fear of contracting COVID-19 (little fear, depression: OR: 1.81 [95% CI 1.01–3.23], some fear, anxiety: OR: 2.52 [95% CI: 1.31–4.83]). Probable depression was associated with longer durations of homelessness (OR: 1.004, [95% CI: 1.001–1.007]. Conclusions: Probable depression and anxiety are highly prevalent in homeless individuals throughout. Key predictors may help to identify individuals in need and design targeted interventions. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the viral spike proteins, which are key structural components that mediate host cell binding and entry and alter downstream signaling through multiple interactions with endothelial surface receptors. Endothelial dysfunction is a central consequence of COVID-19, contributing to vascular inflammation, barrier disruption, thrombosis, and multi-organ injury affecting the pulmonary, cardiovascular, cerebral, and renal systems. Emerging evidence demonstrates that spike protein-mediated effects, independent of productive viral infection, disrupt endothelial homeostasis through angiotensin-converting enzyme 2 (ACE2) dysregulation, integrin engagement, altered calcium signaling, junctional protein remodeling, oxidative stress, and pro-inflammatory and pro-apoptotic pathways. This review is intentionally focused on spike (S) protein-driven mechanisms of endothelial dysfunction; pathogenic vascular effects attributed to other SARS-CoV-2 structural proteins, including the nucleocapsid (N) protein, are beyond the scope of this discussion. In this review, we synthesize current experimental and translational data detailing the molecular mechanisms by which the SARS-CoV-2 spike protein drives endothelial dysfunction across multiple organ systems and discuss potential therapeutic strategies aimed at preserving endothelial integrity in acute COVID-19 and its long-term vascular sequela. Full article

Background: Coronavirus disease 2019 (COVID-19) vaccines deliver mRNA packaged in lipid nanoparticles via intramuscular injection. This study investigated several factors influencing antibody production patterns and adverse reactions after vaccination with COVID-19 vaccines. Methods: Among the participants of the Iwaki Health Promotion Project (IHPP), 211 individuals who consented to this study were surveyed regarding antibody titers and adverse reaction symptoms following vaccination. A machine learning approaches such as ridge regression, elastic-net, light gradient boosting, and neural network were applied to extract the variables, and Bayesian network analysis was applied to explore causal relationships between health data and the multi-omics dataset obtained from the IHPP health checkups. Results: Females with lower levels of free testosterone experienced more adverse reactions than males. Moreover, the immune system is more active in younger individuals, causing adverse reactions and higher antibody production. The Spikevax vaccine induced adverse reaction symptoms with higher antibody production in cases of fever. Meanwhile, drinking 2–3 cups of green tea daily seemed to be effective in increasing antibody production. Factors increasing side effect risk include blood natural killer cell count and muscle quality in the vaccinated arm. Plasma metabolome metabolite concentrations, tongue coating bacterial colonization, and folate intake were also identified as factors influencing side effect risk. Furthermore, characteristics of participants at risk for fever symptoms included longer telomere length, higher antibody production patterns, and higher CD4-positive T cell counts. Conclusions: Further investigation of these identified influencing factors is expected to clarify the rationale for new vaccine development and identify lifestyle and dietary habits that enhance vaccine efficacy. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children presents with a heterogeneous clinical spectrum, whereas multisystem inflammatory syndrome in children (MIS-C) is a distinct immunological entity characterized by a hyperinflammatory phenotype and a distinct biological architecture. Identifying routine biomarkers with early discriminatory utility is essential for rapid differentiation between MIS-C and coronavirus disease 2019 (COVID-19). Methods: We conducted a retrospective comparative study of 144 pediatric patients with COVID-19 or MIS-C admitted to a single specialized medical center. The analyses integrated classical statistical methods, Benjamini–Hochberg false discovery rate correction (FDR), penalized regression models, and machine learning algorithms to identify biomarkers with discriminative value, using only routine laboratory tests. Results: MIS-C was associated with an intense inflammatory profile, characterized by increases in C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), lymphopenia, and selective electrolyte disturbances, highlighting a coherent biological architecture. In contrast, COVID-19 showed limited associations with traditional inflammatory markers. Predictive models identified a stable core of biomarkers with excellent performance in Random Forest analysis (area under the curve, AUC = 0.95), and reproducible thresholds (CRP ~3.7 mg/dL, NLR ~3.3, PLR ~376; potassium ~4.2 mmol/L). These findings were independently confirmed using penalized Ridge regression, where the reduced model achieved superior discrimination compared to the full 13-variable model (AUC = 0.93 vs. 0.89) and maintained stable performance under internal cross-validation, reinforcing the clinical relevance of this compact biomarker panel. Conclusions: MIS-C is clearly distinguished from COVID-19 by a specific and reproducible immunological signature. The identified biomarkers may represent a potential foundation for the development of simple clinical algorithms for pediatric triage and risk stratification, opening the prospect of a simplified scoring tool applicable in emergency settings. Full article

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has had major social and economic consequences worldwide. Whole genome sequencing (WGS) is essential for genomic monitoring, enabling tracking of viral evolution, detection of emerging variants, and identification of introductions and transmission chains to inform timely public health responses. Here, we compile and harmonize SARS-CoV-2 genomic data generated by multiple laboratories across Kazakhstan together with publicly available sequences to provide a national overview of genomic dynamics across successive epidemic waves from 2020 to 2022. We analyzed 4462 genomes deposited in GISAID (including 340 generated in this study), of which 3299 passed Nextclade quality filters, and summarized lineage turnover across major phases (pre-VOC, Alpha, Delta, Omicron BA.1/BA.2, Omicron BA.4/BA.5, and a later recombinant-dominant period). Sequencing intensity varied markedly over time (0.60‰ of confirmed cases during Delta vs. 11.57‰ during the Omicron BA.5 wave), suggesting that lineage diversity and persistence may be underestimated. Pre-VOC circulation included ≥12 Pango lineages with evidence of multiple introductions and sustained local transmission, including a Kazakhstan-restricted B.4.1 lineage that emerged in Nur-Sultan/Astana and disappeared after April 2020. The Tengizchevroil oilfield outbreak comprised B.1.1 viruses with phylogenetic support for ≥three independent introductions. Alpha and Omicron waves were characterized by repeated introductions and heterogeneous origins, whereas Delta was dominated by AY.122 with an additional distinct AY.122 cluster; a notable BF.7 local transmission event was observed during BA.5. We also highlight locally enriched non-lineage-defining mutations. Overall, recurrent importations and variable local amplification shaped SARS-CoV-2 dynamics in Kazakhstan, while interpretation is constrained by strongly time-skewed sequencing. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a wide range of clinical manifestations modulated by genetic factors. The aim of this study was to identify genetic determinants of severe COVID-19 affecting protein sequence to gain insight into disease pathogenesis. Variants prioritized in two patients requiring lung transplant were tested in the Milan FOGS cohort (487/869 cases/controls), highlighting an independent association between the p.F8S low-frequency variant of interferon alpha receptor 2 gene (IFNAR2) and severe disease (OR = 1.73 [1.24–2.42], p = 0.001), replicated in the COVID-19 Host Genetics Initiative cohort (26,167/2,061,934 cases/controls). In the FOGS cohort, the p.F8S variant was linked to higher circulating IL-6 levels. In keeping, bulk transcriptomic analysis in PBMCs at the peak of infection (n = 57) showed that carriers of the p.F8S variant had upregulation of immune signaling and pathogens response (p < 0.05). Functional flow cytometry experiments in healthy donors (n = 12) revealed that membrane IFNAR2 protein expression was reduced in B lymphocytes, but higher in dendritic cells (p < 0.05). Finally, by interrogating a public scRNAseq resource of PBMC of people with COVID-19, we showed that p.F8S carriers had upregulation of immune pathways specifically in dendritic cells (p < 0.05). These results suggest that the p.F8S variant may influence COVID-19 severity by enhancing adaptive immune response, thereby favoring inflammation. Full article

Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer’s Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection. Full article

SARS-CoV-2, the virus responsible for coronavirus disease COVID-19, is a highly transmissible pathogen that has caused substantial global morbidity and mortality. The ongoing COVID-19 pandemic caused by this virus has had a significant impact on public health and the global economy. One approach to combating COVID-19 is the development of broadly neutralizing antibodies for prevention and treatment. In this work, we performed an in silico ligand-based screening of the PDB database to search for unique anti-SARS-CoV-2 motifs. The collected data were organized and presented in a classified SARS-CoV-2 Ligands Database, categorized based on the number of ligands and structural components of the spike glycoprotein. The database contains 1797 entries related to the structures of the spike glycoprotein (UniProt ID: P0DTC2), including both full-length molecules and their fragments (individual domains and their combinations) with various ligands, such as angiotensin-converting enzyme II and antibodies. The database’s capabilities allow users to explore various datasets according to the research objectives. To search for motifs in the receptor-binding domain (RBD) most frequently involved in antibody binding sites, antibodies were classified into four classes according to their location on the RBD; for each class, special binding motifs are revealed. In the RBD binding sites, specific tyrosine-containing motifs were found. Data obtained may help speed up the creation of new antibody-based therapies, and guide the rational design of next-generation vaccines. Full article

Numerous factors contributed to coronavirus 2019 (COVID-19) disease recovery and death rates. In many countries, socioeconomics, morbidities, the experience of symptoms and access to healthcare services are major contributors to recovery and death rates. A retrospective cohort study was conducted to determine the morbidity, mortality, survival probability, and risk factors associated with COVID-19 among children in the Free State province, South Africa. A total of 846 patients’ records were used in the study. Using SPSS version 28 software, survival probability was determined using Kaplan–Meier estimation curves and Cox regression was used to determine the effect of sociodemographics and clinical manifestation information on time of death. The COVID-19 mortality rate was 13.12% in our study. There were more female patients (60%) than male patients (40%). In total, 71 patients had two or more morbidities, while 414 patients were asymptomatic. Patients between 5 and 18 years old were at twice the risk of dying of COVID-19, and male children were at a higher risk as well. Having more than one symptom was also a risk for dying in this study. Severe COVID-19 is attributed to numerous factors, and these are closely associated with surrounding environments and public health systems. The findings are important for the clinical management of similar diseases and circumstances in the future. Full article

Background and Objectives: Secondary bacterial infection drives poor outcomes in older adults with COVID-19, but age-specific microbiology and its interaction with severity scores are not well defined. We characterized respiratory and pleural pathogens, resistance profiles, and their impact on day-5 SOFA/APACHE II in octogenarians versus younger adults. Methods: We performed a retrospective cohort study of adults with RT-PCR-confirmed coronavirus disease 2019 (COVID-19) at a tertiary infectious diseases center (≥80 years, n = 152; <65 years, n = 327). Respiratory and pleural samples were processed according to EUCAST standards. Identification employed matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Pathogen distributions, susceptibilities, and rates of superimposed pneumonia, empyema, and bacteremia were compared by age, and associations between secondary pneumonia, day-5 SOFA/APACHE II, and 28-day mortality were analyzed. Results: Sputum was obtained in 67.1% of older and 65.7% of younger adults, with numerically higher culture positivity in older patients (73.5% vs. 65.1%). Pathogen spectra were similar, dominated by Streptococcus pneumoniae (24.0% vs. 24.3%), methicillin-susceptible Staphylococcus aureus (MSSA) (18.7% vs. 20.7%), methicillin-resistant Staphylococcus aureus (MRSA) (9.3% vs. 6.4%), and Klebsiella pneumoniae, including extended-spectrum β-lactamase (ESBL)-producing strains. Empyema was more frequent in octogenarians (7.9% vs. 3.1%), and pleural cultures were usually positive. Meropenem retained 100% activity against ESBL-producing K. pneumoniae and Pseudomonas in both strata. In ≥80-year-olds, superimposed pneumonia was associated with higher day-5 SOFA (6.6 vs. 5.5) and APACHE II (24.3 vs. 21.0) scores and markedly increased 28-day mortality (37.5% vs. 9.8%). Conclusions: In octogenarians with COVID-19, secondary bacterial pneumonia and empyema are frequent, microbiologically similar to younger adults, and strongly amplify organ dysfunction and mortality even with largely preserved carbapenem susceptibility. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global COVID-19 pandemic, which led to hundreds of millions of human infections and more than seven million deaths worldwide. Major variants of concern, particularly the Omicron variant and its associated subvariants, can escape the vaccines developed so far to target previous strains/subvariants. Therefore, effective vaccines that broadly neutralize different Omicron subvariants and show good protective efficacy are needed to prevent further spread of Omicron. The spike (S) protein, including its receptor-binding domain (RBD), is a key vaccine target. Methods: Here, we designed a unique mRNA vaccine encoding Omicron-KP.3 RBD based on RBD-truncated S protein backbone of an earlier Omicron subvariant EG.5 (KP3 mRNA), and evaluated its stability, immunogenicity, neutralizing activity, and protective efficacy in a mouse model. Results: Our data showed that the nucleoside-modified, lipid nanoparticle-encapsulated mRNA vaccine was stable at various temperatures during the period of detection. In addition, the vaccine elicited potent antibody responses with broadly neutralizing activity against multiple Omicron subvariants, including KP.2, KP.3, XEC, and NB.1.8.1. This mRNA vaccine protected immunized transgenic mice from challenge with SARS-CoV-2 Omicron-KP.3. Immune serum also protected against subsequent virus challenge, with the level of protection associating positively with the serum neutralizing antibody titer. Conclusions: Taken together, the data presented herein suggest that this newly designed mRNA vaccine has potential against current and future Omicron subvariants. Full article

Background: Personal protective measures help prevent infection and disease transmission during health crises such as Coronavirus disease 2019 (COVID-19). Populations facing barriers to adhering to these measures are more vulnerable to the health crisis. This study investigated the association of social drivers of health (SDoH), self-efficacy, and adverse substance use behavior changes with ability to practice COVID-19 personal protective behaviors among persons who inject drugs (PWID) with hepatitis C virus (HCV) infection history. Methods: This study used the Hepatitis C Real Options (HERO) study’s COVID-19 survey data (n = 157). The association of inability to practice COVID-19 personal protective behaviors (hand washing, social distancing, etc.) with (a) SDoH difficulties (employment, housing, etc.); (b) adverse substance use behavior change (overdose, injecting behavior, etc.); and (c) self-efficacy was tested using logistic regression. Results: Inability to practice any personal protective behaviors was more likely among those experiencing any vs. no SDoH difficulties [adjusted odds ratio (aOR) (95% confidence interval (CI))] = 4.57 (1.57, 16.40); p = 0.003] but less likely for those with higher overall self-efficacy [aOR (95% CI) = 0.55 (0.32, 0.93); p = 0.025] and self-efficacy for setting goals [aOR (95% CI) = 0.63 (0.40, 0.96); p = 0.031]. The association between adverse substance use behavior changes and the outcome was not significant. Conclusions: Greater SDoH difficulties and lower self-efficacy were associated with greater inability to practice COVID-19 personal protective behaviors. Interventions to meet SDoH-related challenges and increase self-efficacy could help encourage practice of personal protective behaviors and economically reduce disease burden during health crises. Full article

The COVID-19 pandemic has profoundly affected societies around the world. Although the emergency phase of coronavirus disease 2019 (COVID-19) has ended, the threat it poses remains persistent. This review aims to clarify the mechanisms of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection to support effective management of the disease. A central focus is the host cellular response to the viral infection, with particular emphasis on the role of cytokines. Cytokines play a dual role in antiviral defense: they contribute to the inhibition of viral replication and facilitate the clearance of pathogens, yet dysregulated cytokine responses can result in severe immunopathology. Interferons (type I, type II, and type III) and other cytokines are pivotal in activating intracellular antiviral mechanisms and in orchestrating the recruitment of immune cells through extracellular signaling. Effective immune responses to viral infections are governed not only by primary immune cells—such as dendritic cells, T lymphocytes, and B lymphocytes—but also by the local cytokine milieu shaped by infected and neighboring cells. Given the presence of endogenous inhibitors and autoantibodies in vivo, it is essential to evaluate the functional activity of cytokines in clinical samples. We propose a novel approach to quantify biologically active cytokine levels. Full article

During the Coronavirus Disease 2019 (COVID-19) pandemic, global awareness of infectious diseases increased markedly. Many infectious diseases are transmitted through direct or indirect contact with biological fluids containing pathogens such as viruses and bacteria. This risk is particularly pronounced in environments used by large numbers of unspecified individuals. Public restrooms, therefore, raise significant hygienic concerns, as toilet seats may serve as vectors for indirect transmission. To mitigate this risk, this study proposes a novel toilet seat equipped with an automatic cleaning function. Specifically, after use, the seat surface is automatically wiped by a cleaning cloth, eliminating the need for manual cleaning by staff. A fundamental operational concept is established, emphasizing the determination of an appropriate cleaning initiation timing that allows the cleaning sequence to be completed without compromising user convenience. Based on this concept, a belt–pulley type prototype is developed, and the effectiveness of the proposed cleaning sequence is verified. Subsequently, the prototype is further improved through the introduction of a flexible-rack mechanism. The control methodology, including the design of the electronic circuitry, is described in detail. Using the improved prototype, extensive simulations and experimental evaluations were conducted. The results showed that battery capacity declined at an approximately constant rate of 3% per 10 cycles, with about 70% remaining after 100 cycles. In addition, a single reciprocating cleaning cycle removed over 95% of artificially applied stains across the entire toilet seat. Additional evaluation results are presented in detail. Full article

The Coronavirus Disease 2019 (COVID-19) pandemic and its prolonged effects have been widely discussed on social media, and these discussions have been analyzed in various studies. A long-term analysis of Twitter (now “X”) posts regarding COVID-19 vaccination is essential for informing policy and improving public health communication strategies. In addition, to prevent the spread of infectious diseases, it is crucial to rapidly promote vaccination while mitigating the impact of negative sentiment toward vaccination on social media platforms. Therefore, identifying the key factors behind negative discussions is important for guiding policy decisions and shaping responses. In this study, we collected Japanese tweets (posts) containing the words “Corona” and “vaccine” that were posted from February 2021 to December 2022. The results indicate that negative sentiment was primarily driven by concerns about adverse reactions and general fear and anxiety, which were particularly prominent before vaccination for the general public began, as well as mentions of pain during and after vaccination. While concerns about adverse reactions persisted throughout the analysis period, their prominence decreased over time as positive reactions became more frequent. Our findings provide insights into the characteristics and key factors behind negative discussions on COVID-19 vaccination in the Japanese context and may help improve public health communication strategies. Full article