Search Results (2,567)

The coronavirus disease 2019 (COVID-19) pandemic has put a renewed focus on the value of vaccines in combatting potentially life-threatening diseases. The primary aim was to conduct a longitudinal study on the dispensing patterns of vaccines (from 2017 to 2021) in a section of the private healthcare sector in South Africa. A descriptive cross-sectional pharmacoepidemiological study on health insurance data covering 5 years was conducted. The study included all vaccines available on the South African market (childhood, adult, travel, and other vaccines). The study population consisted of 3.8 million individuals. The descriptive statistics were calculated. The vaccine-dispensing patterns were distinctly different in 2021 compared to the preceding four years. The COVID-19 vaccine was introduced in 2021 in South Africa. Although the total number of medical insurance scheme members stayed relatively constant, the number of vaccine claims increased approximately seven-fold in 2021 compared to the average for the preceding four years (2017 to 2020). The tetanus and pneumococcal vaccines were the most dispensed bacterial vaccines, whilst the influenza and COVID-19 vaccines were the most dispensed viral vaccines. COVID-19 vaccines accounted for 55.74% of all vaccines dispensed over the 5 years, and for 85.70% of the vaccines dispensed in 2021. An increase in the number of bacterial vaccines dispensed was observed towards the middle of 2020, which was attributed to the pneumococcal vaccine. Pneumococcal vaccines were administered during the COVID-19 pandemic to prevent morbidity and mortality from co-/secondary infections and superinfections. Similar ongoing studies on vaccine-dispensing patterns in the post-COVID-19 era are necessary, especially since the outbreak of various vaccine-preventable diseases has recently been observed. Full article

Coronavirus disease 2019 (COVID-19) emerged in late 2019 and was declared a pandemic from March 2020 to May 2023, profoundly affecting public health systems, economies, and daily life worldwide. University students were among the most impacted groups, facing abrupt transitions to remote learning, social isolation, and increased psychological distress due to academic and personal uncertainties. During the pandemic, few studies have been conducted with this population and so far, none have evaluated factors associated with COVID-19 infection in university students, so this study aimed to evaluate variables associated with COVID-19 infection among university students in southern Brazil. Data were collected from July to November 2020 through an online questionnaire addressing lifestyle and health, with participation from 1533 students. Among the variables analyzed, statistically significant associations with COVID-19 infection were identified for age, occupation, use of continuous medication, compliance with social distancing, and self-medication practices. Younger students (18–29 years) and those dedicated solely to studying exhibited higher infection rates. Additionally, participants who reported using continuous medication, not adhering to social distancing measures, or engaging in self-medication were significantly more likely to have contracted COVID-19. These results help outline risk profiles within the university student population and contribute to improved preparedness for future disease outbreaks. Furthermore, they underscore attitudes and behaviors that may increase vulnerability to infectious diseases, highlighting the importance of targeted health promotion and prevention strategies in this demographic. Full article

Background: The lockdown and other measures for coronavirus disease 2019 (COVID-19) prevention have presented an enormous burden on healthcare systems, causing reorganization in work and lowering the number of elective hospitalizations, along with a consequent reduction in hospital-acquired infections and bacteremia. The aim of this study was to examine the influence of the COVID-19 pandemic on the diagnosis and management of infective endocarditis (IE). Methods: The study included 111 patients admitted for IE from 1 January 2017 to 31 December 2021. They were divided in two groups chronologically according to the COVID-19 pandemic: the first group consisted of patients before the pandemic (n = 85), while the second group consisted of patients during the pandemic (n = 26). Results: Before the pandemic there were 2.26 ± 1.41 cases/month with diagnosis of IE, while during the pandemic there were only 1.14 ± 1.15 cases/month (p = 0.004). IE patients during the pandemic were younger (53 [41–65] vs. 68 [52–74] years; p < 0.05). A similar number of patients underwent surgical treatment before and during COVID-19 (53% vs. 67%; p = 0.210) and 30-day mortality was comparable (28% vs. 22%; p = 0.539). Conclusion: The COVID-19 pandemic and lockdown measures have led to a reduction in the number of patients with IE, although this change did not influence management strategies and mortality. Full article

Background/Objectives: Coronavirus disease 2019 (COVID-19) has been a global pandemic since 2019, but effective therapeutic treatments for it remain limited. Shuqing Granule (SG) is a traditional Chinese medicine containing ingredients such as indirubin, shinpterocarpin, naringenin, and quercetin. It exhibits anti-inflammatory and antiviral activities as well as broad-spectrum antiviral effects, yet its potential role in the treatment of COVID-19 remains unclear. This study thus aimed to explore the therapeutic effects of SG on COVID-19, with a focus on its potential anti-SARS-CoV-2 activity linked to these bioactive ingredients. Methods: The potential therapeutic ability of SG was investigated by combining network pharmacology, molecular docking, and experimental verification. First, key ingredients in SG and their corresponding targets, as well as COVID-19-related targets, were identified. Then, enrichment analyses were performed to highlight potential key pathways. Additionally, molecular docking was conducted to assess the binding capacity of the key ingredients to ACE2. Finally, experiments such as Western blot and ELISA were conducted to verify the effect of SG. Results: The results showed that 15 key ingredients such as quercetin in SG could affect overlapping targets such as RELA. Molecular docking results showed that key ingredients in SG, such as isoliquiritigenin, formononetin, shinpterocarpin, indirubin, naringenin, kaempferol, and 7-Methoxy-2-methylisoflavone, might bind to angiotensin-converting enzyme II (ACE2)—a critical receptor in the process of COVID-19 infection—thereby exerting antiviral effects. Experiments such as Western blot and ELISA further demonstrated that SG could reduce inflammation induced by the SARS-CoV-2 S1 protein by 50%. This effect might be achieved by downregulating ACE2 expression by 1.5 times and inhibiting the NF-κB signaling pathway. Conclusions: This study confirmed that SG has potential as a candidate for COVID-19 treatment. It also provided a new approach for the application of traditional Chinese medicine in combating the virus. Full article

Proteolysis-targeting chimera (PROTAC) technology has demonstrated remarkable progress in tumor therapy, attributed to its unique capability of catalytically degrading “undruggable” targets. In the context of the ongoing global health threat posed by the Coronavirus Disease 2019 (COVID-19) pandemic, the application scope of PROTAC technology has been gradually extended to the field of antiviral research. Unlike traditional small molecule inhibitors, PROTAC employs an “event-driven” mechanism to achieve ubiquitination-mediated degradation of target proteins. This approach holds great promise in addressing challenges such as drug resistance, targeting host-dependent factors, and high-mutagenic viral proteins. This article provides a comprehensive review of the application progress of PROTAC technology in antiviral therapy, with a particular emphasis on successful cases across a range of viral pathogens, including Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), influenza virus, and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Additionally, it delves into the challenges encountered in this field and ponders future development directions. Through the integration of the latest research findings, this article proposes a dual-target degradation strategy based on the host–pathogen interaction interface. These proposals aim to offer theoretical support for the clinical translation of antiviral PROTACs. Full article

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought to light unexpected complications beyond respiratory illness, including effects on kidney function and a potential link to kidney stone disease (KSD). This review proposes a novel framework connecting COVID-19-induced epigenetic reprogramming to disruptions in mitochondrial sulfur metabolism and the pathogenesis of kidney stones. We examine how SARS-CoV-2 interferes with host methylation processes, leading to elevated homocysteine (Hcy) levels and impairment of the trans-sulfuration pathway mechanisms particularly relevant in metabolic disorders such as homocystinuria. These epigenetic and metabolic alterations may promote specific kidney stone subtypes through disrupted sulfur and oxalate handling. Additionally, we explore the role of COVID-19-associated gut dysbiosis in increasing oxalate production and driving calcium oxalate stone formation. Together, these pathways may accelerate the transition from acute kidney injury (AKI) to chronic KSD, linking viral methylation interference, sulfur amino acid imbalance, mitochondrial dysfunction, and microbiota changes. Unlike earlier reviews that address these mechanisms separately, this work offers an integrated hypothesis to explain post-viral renal lithogenesis and highlights the potential of targeting sulfur metabolism and redox pathways as therapeutic strategies for KSD triggered or aggravated by viral infections such as COVID-19. Full article

Background: Preschool-aged children can have difficulty adhering to infection control measures and were affected during the Omicron wave of the coronavirus disease 2019 (COVID-19) pandemic. However, the impacts of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination on viral load in this age group remain poorly understood. This study aimed to investigate the relationship between previous SARS-CoV-2 infection, COVID-19 vaccination, and viral load or clinical severity in preschool-aged children infected during the Omicron variant epidemic in Japan. Methods: This prospective observational study investigated 107 children aged 1–75 months who were diagnosed with COVID-19 between May and September 2023. Rapid antigen (Ag) tests were performed on days 1 and 5 or 6, and results were visually graded into four categories (–, ±, 1+, or 2+). Ag results were validated against quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) cycle threshold (Ct) values. Clinical parameters, including vaccination status, previous infection, age, maximum body temperature, and fever duration, were analyzed using multivariate regression models. Results: Higher Ag loads (1+/2+) were more frequently observed in younger children who had not experienced prior infection or full vaccination. Prior infection and vaccination were independently linked to lower Ag loads and reduced maximum body temperature. Many unvaccinated and infection-naïve children continued to show elevated Ag levels on day 5 or 6, corresponding to Ct values suggestive of potential infectivity. Conclusions: Prior SARS-CoV-2 infection and vaccination were linked to lower viral loads and milder febrile responses among preschool-aged children. These findings enhance our understanding of infection dynamics in this age group and may inform future discussions on public health strategies in pediatric settings. Full article

Background and Objectives: Ankle fractures represent one of the most common injuries to the lower limb, particularly impacting women and the elderly. The coronavirus disease 2019 (COVID-19) pandemic greatly disrupted both the incidence of these fractures and their treatment patterns globally. This retrospective epidemiological study analyzed 1010 cases of ankle fractures treated at the Orthopedics Department of Policlinico University Hospital in Catania from 2018 to 2023. The study aimed to evaluate trends in incidence, patient demographics, fracture types, treatment modalities, and hospital stay across the pre-COVID-19, COVID-19, and post-COVID-19 periods. Materials and Methods: A retrospective observational study was conducted including all patients diagnosed with ankle fractures from 1 January 2018 to 31 December 2023. Data were collected from hospital medical records using ICD-9-CM codes and radiographic classification systems (Danis–Weber, Lauge-Hansen, and AO/OTA). Variables analyzed included demographics, fracture type and side, treatment modality, and hospitalization details. Statistical analyses were performed using t-tests, chi-square tests, and linear regression, with significance set at p < 0.05. Results: In 2020, there was a 31.7% decrease in fracture incidence. Although overall fracture rates rebounded after COVID-19, they did not reach pre-pandemic levels. During the pandemic, trimalleolar fractures increased significantly, occurring more frequently in older women, likely due to bone fragility. The rate of surgical treatments rose during and after the pandemic, with a distinct shift from ORIF to external fixation. Hospital stays were longer, especially for patients with cardiovascular risk factors. Conclusions: The pandemic significantly altered the epidemiology, treatment strategies, and outcomes of ankle fractures. These findings highlight the necessity for adaptable care models and preventive strategies, particularly for vulnerable populations such as older women. Full article

During the coronavirus 2019 pandemic, sports activities were restricted, raising concerns about their impact on the physical condition of adolescent athletes, which remained largely unquantified. This study was designed with two primary objectives: first, to precisely quantify and elucidate the differences in the physical condition of adolescent athletes before and after activity restrictions due to the pandemic; and second, to innovatively develop and validate a non-contact medical checkup application. Medical checks were conducted on 563 athletes designated for sports enhancement. Participants were junior high school students aged 13 to 15, and the sample consisted of 315 boys and 248 girls. Furthermore, we developed a smartphone application and compared self-checks using the application with in-person checks by orthopedic surgeons to determine the challenges associated with self-checks. Statistical tests were conducted to determine whether there were statistically significant differences in range of motion and flexibility parameters before and after the pandemic. Additionally, items with discrepancies between values self-entered by athletes using the smartphone application and values measured by specialists were detected, and application updates were performed. Student’s t-test was used for continuous variables, whereas the chi-square test was used for other variables. Following the coronavirus 2019 pandemic, athletes were stiffer than during the pre-pandemic period in terms of hip and shoulder joint rotation range of motion and heel–buttock distance. The dominant hip external rotation decreased from 53.8° to 46.8° (p = 0.0062); the non-dominant hip external rotation decreased from 53.5° to 48.0° (p = 0.0252); the dominant shoulder internal rotation decreased from 62.5° to 54.7° (p = 0.0042); external rotation decreased from 97.6° to 93.5° (p = 0.0282), and the heel–buttock distance increased from 4.0 cm to 10.4 cm (p < 0.0001). The heel–buttock distance and straight leg raising angle measurements differed between the self-check and face-to-face check. Although there are items that cannot be accurately evaluated by self-check, physical condition can be improved with less contact by first conducting a face-to-face evaluation under appropriate guidance and then conducting a self-check. These findings successfully address our primary objectives. Specifically, we demonstrated a significant decline in the physical condition of adolescent athletes following pandemic-related activity restrictions, thereby quantifying their impact. Furthermore, our developed non-contact medical checkup application proved to be a viable tool for monitoring physical condition with reduced contact, although careful consideration of measurable parameters is crucial. This study provides critical insights into the long-term effects of activity restrictions on young athletes and offers a practical solution for health monitoring during infectious disease outbreaks, highlighting the potential for hybrid checkup approaches. 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

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

Long-term source apportionment of PM_2.5 during high-pollution periods is essential for achieving sustained reductions in both PM_2.5 levels and their health impacts. This study conducted PM_2.5 sampling in Shenzhen from January to March over the years 2021–2024 to investigate the long-term impact of coronavirus disease 2019 and the short-term impact of the Spring Festival on PM_2.5 levels. The measured average PM_2.5 concentration during the research period was 22.5 μg/m³, with organic matter (OM) being the dominant component. Vehicle emissions, secondary sulfate, secondary nitrate, and secondary organic aerosol were identified by receptor model as the primary sources of PM_2.5 during the observational periods. The pandemic led to a decrease of between 30% and 50% in the contributions of most anthropogenic sources in 2022 compared to 2021, followed by a rebound. PM_2.5 levels in January–March 2024 dropped by 1.4 μg/m³ compared to 2021, mainly due to reduced vehicle emissions, secondary sulfate, fugitive dust, biomass burning, and industrial emissions, reflecting Shenzhen’s and nearby cities’ effective control measures. However, secondary nitrate and fireworks-related emissions rose significantly. During the Spring Festival, PM_2.5 concentrations were 23% lower than before the festival, but the contributions of fireworks burning exhibited a marked increase in both 2023 and 2024. Specifically, during intense peak events, fireworks burning triggered sharp, short-term spikes in characteristic metal concentrations, accounting for over 50% of PM_2.5 on those peak days. In the future, strict control over vehicle emissions and enhanced management of fireworks burning during special periods like the Spring Festival are necessary to reduce PM_2.5 concentration and improve air quality. Full article

Although it is more than a century since it was first marketed, acetaminophen remains one of the most popular analgesic agents. In addition, acetaminophen has recently been applied to multimodal analgesia in combination with non-steroidal anti-inflammatory drugs, and its consumption significantly increased during the pandemic of coronavirus disease 2019 as well as diclofenac and ibuprofen. However, the detailed mode of analgesic action of acetaminophen is still unclear. In the present study, we comprehensively discuss conventional, recognized, and postulated mechanisms of analgesic acetaminophen and highlight the current mechanistic concepts while comparing with diclofenac and ibuprofen. Acetaminophen inhibits cyclooxygenase with selectivity for cyclooxygenase-2, which is higher than that of ibuprofen but lower than that of diclofenac. In contrast to diclofenac and ibuprofen, however, anti-inflammatory effects of acetaminophen depend on the extracellular conditions of inflamed tissues. Since the discovery of cyclooxygenase-3 in the canine brain, acetaminophen had been hypothesized to inhibit such a cyclooxygenase-1 variant selectively. However, this hypothesis was abandoned because cyclooxygenase-3 was revealed not to be physiologically and clinically relevant to humans. Recent studies suggest that acetaminophen is deacetylated to 4-aminophenol in the liver and after crossing the blood–brain barrier, it is metabolically converted into N-(4-hydroxyphenyl)arachidonoylamide. This metabolite exhibits bioactivities by targeting transient receptor potential vanilloid 1 channel, cannabinoid receptor 1, Cav3.2 calcium channel, anandamide, and cyclooxygenase, mediating acetaminophen analgesia. These targets may be partly associated with diclofenac and ibuprofen. The perspective of acetaminophen as a prodrug will be crucial for a future strategy to develop analgesics with higher tolerability and activity. Full article

The coronavirus disease 2019 (COVID-19) pandemic has led to substantial health and financial burdens worldwide, and vaccines provide hope for reducing the burden of this pandemic. However, vaccinated people remain at risk for SARS-CoV-2 infection. Genome-wide association studies (GWASs) may identify potential genetic factors involved in the development of COVID-19 breakthrough infections (BIs); however, very few or no GWASs have been conducted for COVID-19 BI thus far. We conducted a GWAS and detailed bioinformatics analysis on COVID-19 BIs in a European population via the UK Biobank (UKBB). We conducted a series of analyses at different levels, including SNP-based, gene-based, pathway, and transcriptome-wide association analyses, to investigate genetic factors associated with COVID-19 BIs and hospitalized infections. The polygenic risk score (PRS) and Hoeffding’s test were performed to reveal the genetic relationships between BIs and other medical conditions. Two independent loci (LD-clumped at r² = 0.01) reached genome-wide significance (p < 5 × 10⁻⁸), including rs36170929, which mapped to LOC102725191/VWDE, and rs28645263, which mapped to RETREG1. A pathway enrichment analysis highlighted pathways such as viral myocarditis, Rho-selective guanine exchange factor AKAP13 signaling, and lipid metabolism. The PRS analyses revealed significant genetic overlap between COVID-19 BIs and heart failure and between HbA1c and type 1 diabetes. Genetic dependence was also observed between COVID-19 BIs and asthma, lung abnormalities, schizophrenia, and type 1 diabetes on the basis of Hoeffding’s test. This GWAS revealed two significant loci that may be associated with COVID-19 BIs and a number of genes and pathways that may be involved in BIs. Genetic overlap with other diseases was identified. Further studies are warranted to replicate these findings and elucidate the mechanisms involved. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease pandemic. The virus primarily spreads through person-to-person contact via aerosols and droplets, contributing to high case numbers and related morbidities. SARS-CoV-2 targets the respiratory tract, causing acute respiratory distress syndrome, particularly in immunocompromised individuals such as those with cystic fibrosis (CF). CF is a life-threatening genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to impaired respiratory function and recurrent severe respiratory symptoms. Despite their potential vulnerability, CF patients have shown a lower incidence of severe COVID-19, suggesting protective factors against SARS-CoV-2. Differential expression of the ACE2 receptor, crucial for viral entry, and other host factors, such as TMPRSS2, may play a role in this resistance to SARS-CoV-2. Analyzing the genomics and transcriptomics profiles of CF patients could provide insights into potential resistance mechanisms. The potential resistance mechanisms include blood and extracellular ATP levels, a deleted/dysfunctional CFTR gene, ACE and ACE2 regulation and expression, ACE and ACE2 polymorphism effects, host proteins and SARS-CoV-2 interactions, and SMN1 and ACE/ACE2 interactions. This review discusses the underlying factors and potential resistance mechanisms contributing to CF patients’ responses to SARS-CoV-2 infection. The review provides an opportunity to further investigate future therapy and research through understanding the underlying potential resistance mechanisms exhibited by CF patients against SARS-CoV-2, including ACE and ACE2 polymorphisms. Full article