Search Results (18,057)

Determining the transmission routes of pathogens in indoor environments is challenging, with most studies limited to specific case analyses and pilot experiments. When pathogens are instantaneously released by a patient in an indoor environment, the peak infection risk may not occur immediately but may instead appear at a specific moment during the pathogen’s spread. We developed a concise model to describe the temporal crest of infection risk. The model incorporates the transmission and degradation characteristics of aerosols and surface particles to predict infection risks via air and surface routes. Only four real-world outbreaks met the criteria for validating this phenomenon. Based on the available data, norovirus is likely to transmit primarily via surface touch (i.e., the fomite route). In contrast, crests of infection risk were not observed in outbreaks of respiratory diseases (e.g., SARS-CoV-2), suggesting a minimal probability of surface transmission in such cases. The new model can serve as a preliminary indicator for identifying different indoor pathogen transmission routes (e.g., food, air, or fomite). Further analyses of pathogens’ transmission routes require additional evidence. Full article

The COVID-19 pandemic was a profoundly influential global occurrence in recent history, impacting daily life, economics, and healthcare systems for an extended period. The abundance of data has been essential in creating models to simulate and forecast the dissemination of infectious illnesses, aiding governments and health organizations in making educated decisions. This research primarily focuses on designing a control technique that incorporates the five most important inputs that impact the spread of COVID-19 on the Romanian territory. Quantitative analysis and data filtering are two crucial aspects to consider when developing a mathematical model. In this study the transfer function principle was used as the most accurate method for modeling the system, based on its superior fit demonstrated in a previous study. For the control strategy, a PI (Proportional-Integral) controller was designed to meet the requirements of the intended behavior. Finally, it is showed that for such complex models, the chosen control strategy, combined with fine tuning, led to very accurate results. Full article

Background/Objectives: Cognitive impairment in older adults has emerged as a growing public health concern, particularly in relation to COVID-19 infection and its associated neuropsychiatric symptoms. The identification of modifiable risk factors may contribute to the development of targeted preventive strategies. This study aimed to assess predictors of cognitive impairment in older adults with and without recent SARS-CoV-2 infection. Methods: A prospective cohort study was conducted from June 2023 to March 2024 at a tertiary hospital in western Mexico. Adults aged 65 years or older with confirmed SARS-CoV-2 infection within the previous six months, along with uninfected controls, were enrolled. Cognitive function (Mini-Mental State Examination), depression (PHQ-9), anxiety (Geriatric Anxiety Inventory), insomnia (Insomnia Severity Index), functional status (Katz Index and Lawton–Brody Scale), and laboratory markers were evaluated at baseline, three months, and six months. The primary outcome was cognitive impairment at six months. Independent predictors were identified using a multivariable generalized linear mixed-effects model. Results: Among the 111 participants, 20 (18.8%) developed cognitive impairment within six months. Low serum magnesium (adjusted risk ratio [aRR] 2.73; 95% CI 1.04–7.17; p = 0.041) and depression (aRR 5.57; 95% CI 1.88–16.48; p = 0.002) were independently associated with a higher risk. A significant synergistic among COVID-19, depression, and hypomagnesemia was observed (RR 44.30; 95% CI 9.52–206.21; p < 0.001), corresponding to the group with simultaneous presence of all three factors compared to the group with none. Conclusions: Depression and hypomagnesemia appear to be independent predictors of cognitive impairment in older adults with recent COVID-19 infection. These findings suggest potential targets for prevention and support the implementation of routine neuropsychiatric and biochemical assessments in this population. Full article

The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, thus providing abundant resources for the discovery of antiviral candidates. While many candidates have been suggested to have antiviral activity against SARS-CoV-2 infection, few have been validated for their mechanisms, including possible effects on viral entry. This study aimed to identify SARS-CoV-2 entry inhibitors from medicinal herbs and herbal formulas that are known for heat-clearing and detoxifying properties and/or antiviral activities. A SARS-CoV-2 pseudoparticle (SARS-CoV-2pp) system was used to assess mechanism-specific entry inhibition. Our results showed that the methanol extract of Anemarrhena asphodeloides rhizome, as well as the water extracts of Cimicifuga foetida rhizome, Xiao Chai Hu Tang (XCHT), and Sheng Ma Ge Gen Tang (SMGGT), have substantial inhibitory effects on the entry of SARS-CoV-2pps into host cells. Given the observation that Cimicifuga foetida exhibited the most potent inhibition and is a constituent of SMGGT, we further investigated the major compounds of the herb and identified caffeic acid as a bioactive component for blocking SARS-CoV-2pp entry. Entry inhibition of Cimicifuga foetida and caffeic acid was validated on both wild-type and the currently dominant JN.1 strain SARS-CoV-2pp systems. Moreover, caffeic acid was able to both inactivate the pseudoparticles and prevent their entry into pretreated host cells. The results support the traditional use of these herbal medicines and underscore their potential as valuable resources for identifying active compounds and developing therapeutic entry inhibitors for the management of COVID-19. Full article

This study is the first to investigate the performance of ultraviolet germicidal irradiation (UVGI) in underfloor air distribution (UFAD) systems. A simplified mathematical model is developed to predict airborne pathogen transport and inactivation by upper room UVGI in UFAD spaces. The proposed model is substantiated for the SARS-CoV-2 virus as a simulated pathogen through a comprehensive computational fluid dynamics methodology validated against published experimental data of upper room UVGI and UFAD flows. Simulations show an 11% decrease in viral concentration within the upper irradiated zone when a 15 W louvered germicidal lamp is utilized. Finally, a case study on Mycobacterium tuberculosis (M. tuberculosis) bacteria is carried out using the validated simplified model to optimize the use of return air and UVGI implementation, ensuring acceptable indoor air quality and enhanced energy efficiency. Results reveal that the UFAD-UVGI system may consume up to 13.6% less energy while keeping the occupants at acceptable levels of M. tuberculosis concentration and UV irradiance when operated with 26% return air and a UVGI output of 72 W. Full article

The COVID-19 pandemic precipitated unprecedented social isolation measures, profoundly disrupting daily life, educational routines, and mental health worldwide. University students, already susceptible to psychological distress, encountered intensified challenges under remote learning and prolonged confinement. This longitudinal study examined fluctuations in anxiety and mood among 102 Brazilian university students during the pandemic, distinguishing between those solely engaged in academic pursuits and those simultaneously balancing work and study. Data collected via the Brunel Mood Scale and State-Trait Anxiety Inventory in April and July 2021 revealed that students exclusively focused on studies exhibited significant increases in depressive symptoms, anger, confusion, and anxiety, alongside diminished vigor. Conversely, participants who combined work and study reported reduced tension, fatigue, confusion, and overall mood disturbance, coupled with heightened vigor across the same period. Notably, women demonstrated greater vulnerability to anxiety and mood fluctuations, with socioeconomic disparities particularly pronounced among females managing dual roles, who reported lower family income. These findings suggest that occupational engagement may serve as a protective factor against psychological distress during crises, underscoring the urgent need for tailored mental health interventions and institutional support to mitigate the enduring impacts of pandemic-related adversities on the student population. Full article

The repeated occurrence of SARS-CoV-2 variants, largely driven by virus–host interactions, was and will remain a public health concern. Spike protein mutations shaped viral infectivity, transmissibility, and immune escape. From February 2022 to April 2024, a local genomic surveillance program in Verona, Italy, was conducted on 1333 SARS-CoV-2-positive nasopharyngeal swabs via next generation full-length genome sequencing. Spike protein mutations were classified based on their prevalence over time. Mutations were grouped into five categories: fixed, emerging, fading, transient, and divergent. Notably, some divergent mutations displayed a “Lazarus effect,” disappearing and later reappearing in new lineages, indicating potential adaptive advantages in specific genomic contexts. This two-year surveillance study highlights the dynamic nature of spike protein mutations and their role in SARS-CoV-2 evolution. The findings underscore the need for ongoing mutation-focused genomic monitoring to detect early signals of variant emergence, especially among mutations previously considered disadvantageous. Such efforts are critical for driving public health responses and guiding future vaccine and therapeutic strategies. Full article

Human leukocyte antigen class I (HLA-I) molecules present intracellular peptides on the cell surface to enable CD8+ T cells to effectively control viral infections. Many viruses disrupt this antigen presentation pathway to evade immune detection. In this study, we demonstrate that SARS-CoV-2 Nsp1 impairs both the constitutive and interferon-γ (IFN-γ)-induced upregulation of HLA-I. Moreover, Nsp1 also blocks IFN-γ-induced expression of HLA-II. We found that, contrary to previously published work, the early SARS-CoV-2 B 1.1.7 Alpha variant lacking the accessory protein ORF8 retained full capacity to downregulate HLA-I, comparable to an ORF8-expressing wild-type isolate. While ectopic overexpression of ORF8 could reduce HLA-I surface levels, this effect was only observed at high expression levels. In contrast, moderate expression of the viral protein Nsp1 was sufficient to potently suppress both basal and IFN-γ-induced HLA-I, as well as HLA-II expression. To probe the underlying mechanism, we analyzed HLA-I-associated genes in previously published RNA-sequencing datasets and confirmed that Nsp1 reduces expression of components required for HLA-I biosynthesis and antigen processing. These findings identify Nsp1 as a key factor that impairs antigen presentation pathways, potentially contributing to the ability of SARS-CoV-2 to modulate immune recognition. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

SARS-CoV-2 undergoes frequent mutations that drive viral evolution and genomic diversity, influencing transmissibility, immune escape, and disease severity. In this study, we performed whole-genome sequencing on SARS-CoV-2 isolates from patients in New York City and identified several globally rare mutations across multiple viral lineages. The isolates analyzed for rare mutations belonged to three lineages: B.1.1.7 (Alpha), B.1.526 (Iota), and B.1.623. We identified 16 rare mutations (global incidence <1000) in non-structural protein genes, including nsp2, nsp3, nsp4, nsp6, nsp8, nsp13, nsp14, ORF7a, and ORF8. Three of these mutations—located in nsp2, nsp13, and ORF8—have been reported in fewer than 100 individuals worldwide. We also detected five rare mutations in structural proteins (S, M, and N), including two—one in M and one in N—previously reported in fewer than 100 cases globally. We present clinical profiles of three patients, each infected with genetically distinct viral isolates from the three lineages studied. Furthermore, we illustrate a local transmission chain inferred from unique mutation patterns identified in the Omicron genome. These findings underscore the importance of whole-genome sequencing for detecting rare mutations, tracking community spread, and identifying emerging variants with clinical and public health significance. Full article

Background/Objectives: Due to the significant overlap in symptoms between COVID-19 and other respiratory infections, a multiplex PCR-based platform was developed to simultaneously detect 22 respiratory pathogens. Target sequences were retrieved from the GenBank database and aligned using Clustal Omega 2.1 to identify conserved regions prioritized for primer design. Primers were designed using Primer Express^® 3.0.1 and evaluated in Primer Explorer to ensure specificity and minimize secondary structures. A multiplex strategy organized primers into three groups, each labeled with distinct fluorophores (FAM, VIC, or NED), allowing for detection by conventional PCR or capillary electrophoresis (CE). Methods: After reverse transcription for RNA targets, amplification was performed in a single-tube reaction. A total of 340 clinical samples—nasopharyngeal and saliva swabs—were collected from patients, during the COVID-19 pandemic period. The automated analysis of electropherograms enabled precise pathogen identification. Results: Of the samples analyzed, 57.1% tested negative for all pathogens. SARS-CoV-2 was the most frequently detected pathogen (29%), followed by enterovirus (6.5%). Positive results were detected in both nasopharyngeal and saliva swabs, with SARS-CoV-2 predominating in saliva samples. Conclusion: This single-tube multiplex PCR-CE assay represents a cost-effective and robust approach for comprehensive respiratory pathogen detection. It enables rapid and simultaneous diagnosis, facilitating targeted treatment strategies and improved patient outcomes. Full article

Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, specifically its Main Protease (M^pro), in accelerating insulin resistance and metabolic dysfunction in HepG2 cells in vitro. Methods: HepG2 cells were treated with varying concentrations of M^pro (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to assess cytotoxicity and glucose uptake. Based on initial findings, subsequent assays focused on higher concentrations (40, 80, and 160 nmol/mL). The effects of M^pro on cell viability, protein kinase B (AKT) expression, matrix metallopeptidase-1 (MMP1), dipeptidyl peptidase 4 (DPP4), interleukin-6 (IL-6) expression, and lipid peroxidation were investigated. Results: Our findings reveal that the SARS-CoV-2 M^pro treatment led to a concentration-dependent reduction in glucose uptake in HepG2 cells. Additionally, the M^pro treatment was associated with reduced insulin-stimulated AKT activation, particularly at higher concentrations. Inflammatory markers such as IL-6 were elevated in the extracellular medium, while DPP4 expression was decreased. However, extracellular soluble DPP4 (sDPP4) levels did not show a significant change. Despite these changes, cell viability remained relatively unaffected, suggesting that the HepG2 cells were able to maintain overall metabolic functions under M^pro exposure. Conclusions: This study demonstrated the concentration-dependent impairment of hepatic glucose metabolism, insulin signaling, and inflammatory pathways in HepG2 cells acutely exposed to the SARS-CoV-2 M^pro. These findings warrant further investigation to explore the long-term metabolic effects of SARS-CoV-2 and its proteases in the liver and to develop potential therapeutic approaches for post-viral metabolic complications. Full article

Background: The surge in COVID-19 cases during the pandemic created a disease burden. An epidemiological study on COVID-19 is required as not much is known about the impact of containment and mitigation on health. We aimed to compare the epidemiological features during the years of the COVID-19 pandemic in the Vidarbha region in Maharashtra, India, to understand the epidemiology changes throughout the pandemic’s progression. Method: All of the cases reported at our testing centers in Nagpur and its periphery during the three years of the pandemic (i.e., from February 2020 to December 2022) were included. Descriptive analyses of variables of interest and statistical measures were compared. Results: There were 537,320 tests recorded during the study period. Of these, 13,035 (13.29%), 42,909 (13.70%), and 19,936 (15.91%) tested positive in 2020, 2021, and 2022, respectively. Hospitalization decreased from 2020 to 2022. An age group shift from 45 to 16–30 years over the pandemic was noticed. Seasonally, positivity peaked in September (27.04%) in 2020, in April (43.4%) in 2021, and in January in 2022 (35.30%). The estimated case fatality ratio was highest in 2021 (36.68%) over the three years in the hospital setting. Conclusion: Understanding the changing epidemiology of SARS-CoV-2 strengthens our perceptive of this disease, which will aid in improving the healthcare system in terms of both controlling and preventing the spread of COVID-19. Full article

Background/Objectives: This study aimed to evaluate sociodemographic factors, features of the acute infection, and post-infection health status in survivors of COVID-19, assessing their association with post-acute COVID-19 syndrome (PACS). Methods: A multidisciplinary public clinic in Brazil assessed COVID-19 survivors between June 2020 and February 2022. Patients were classified as having PACS or subacute infection (SI). Data on the history of the acute infection, current symptoms, physical examination, and laboratory findings were collected and analyzed using multivariate models with PACS as the outcome. Results: Among the 113 participants, 63.71% were diagnosed with PACS at a median of 130 days (IQR: 53–196) following acute symptom onset. Admission to the intensive care unit was more frequent among individuals with PACS than those with SI (83.3% vs. 65.0% respectively; p = 0.037). Symptoms significantly more prevalent in the PACS group when compared to the SI cohort included hair loss (44.4% vs. 17.1% respectively; p = 0.004), lower limb paresthesia (34.7% vs. 9.8% respectively; p = 0.003), and slow thinking speed (28.2% vs. 0.0% respectively; p < 0.001). Logistic regression revealed that only the time interval between the onset of acute symptoms and the clinical evaluation was independently associated with a PACS diagnosis (β = 0.057; 95% CI: 1.03–1.08; p < 0.001). Conclusions: Patients with PACS had a higher frequency of intensive care unit admission compared to those with subacute infection. However, in the multivariate analysis, the severity of the acute infection did not predict the final diagnosis of PACS, which was associated only with the time elapsed since symptom onset. Full article