Search Results (793)

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

Importance: The coronavirus disease 2019 (COVID-19) was the third leading cause of mortality in the United States for three years in a row. The genetic contributions to disease severity remain unclear and many previously identified single nucleotide polymorphisms (SNPs) have not been replicated nor linked with functional significance. Objective: To identify SNPs associated with mortality among hospitalized COVID-19 patients supplemented by expression quantitative trait loci (eQTL) evidence to infer plausible functional mechanisms related to COVID-19 severity. Design: A quality-controlled genome-wide association study (GWAS) supported by robust gene-level omnibus kernel association tests (SKAT-O), functional prediction, and eQTL analyses of the top GWAS signal. Setting: Massachusetts General Hospital (MGH). Participants: 370 adult ICU patients with SARS-CoV-2 infection and acute hypoxemic respiratory failure and floor patients with mild hypoxemia managed with supplemental oxygen consecutively admitted to MGH between March and June 2020 (Surge 1), and January and March 2021 (Surge 2) with baseline clinical characteristics and demographics collected. Exposures: Low-pass genotyped SNPs from whole blood and aggregated SNP-sets of potential disease susceptibility loci with $\pm$500 kb flanking regions. Main Outcomes & Measures: Genome-wide individual SNP associations and SNP-set associations with mortality outcomes from 370 severe COVID-19 cases. Results: After LD pruning (<0.8) and false discovery rate adjustment (<0.05), we identified rs7420371 G>A of the receptor transporter protein 5 (RTP5) gene as the top independent signal significantly associated with 30- and 60-day mortality among severe COVID-19 patients (OR, 2.32; 95% CI, 1.59–3.39; p = 4.92 × 10⁻⁹ and OR, 2.06; 95% CI, 1.43–2.97; p = 5.43 × 10⁻⁸, respectively). SKAT-O analyses on the RTP5 SNP-set showed associations with both mortality outcomes (p = 5.90 × 10⁻⁵ and 6.17 × 10⁻⁵, respectively). eQTL analysis showed rs7420371 A allele significantly upregulated the mRNA expression of RTP5 in 266 cerebellum tissues, in 277 cerebellar hemisphere tissues, and in 270 cerebral cortex samples. Conclusions & Relevance: We discovered a novel, independent, and potentially functional SNP RTP5 rs7420371 G>A to be significantly associated with COVID-19 mortality. The A allele is significantly associated with elevated mRNA expression of RTP5 in the brain, an important protein coding gene that modulates olfactory binding and taste perceptions in response to SARS-CoV-2 infection. Full article

The utilisation of cardiopulmonary bypass (CPB) during cardiac surgery is often associated with complex haemostatic perturbations, frequently manifesting as a paradoxical risk of both bleeding and thrombosis. This is postulated to be driven by systemic inflammation, endothelial activation and contact activation of the coagulation cascade due to extracorporeal circulation. However, the coronavirus disease 2019 (COVID-19) pandemic revealed a unique hypercoagulable state, termed COVID-19-associated coagulopathy (CAC), also observed in those vaccinated against COVID-19. CAC displays similar physiological manifestations to those of disseminated intravascular coagulation (DIC), characterised by elevated fibrinogen and D-dimer values. The precise pathogenesis of CAC requires further elucidation though proposed mechanisms include: an exaggerated inflammatory response to COVID-19 infection or antibody proliferation due to vaccination, direct epithelial cell damage mediated by angiotensin converting enzyme 2, and ‘hypoxithrombosis’. CAC has since provided a unique framework to understand and potentially mitigate coagulation complications encountered during CPB in the post-pandemic era, as it is no longer sufficient to view COVID-19 as a transient influence on surgical risk. Rather, it must be recognized as a persistent modifier of the haemostatic environment across the population, with direct implications upon patient selection, intraoperative management and postoperative care in cardiac surgery. This review examines the pathological drivers behind CAC alongside the insights obtained from CAC management during ECMO deployment, to investigate the potential translation of such knowledge into improved anticoagulation strategies and monitoring during cardiac surgery. The use of alternative anticoagulants including factor XI inhibitors and the modulation of heparinase activity offers promising avenues to attenuate coagulopathies more commonly observed during CPB in the post-pandemic climate, whilst anti-Xa assays and viscoelastic testing have offered applicability to modern perfusion practices. By bridging the knowledge gained during the pandemic with that of conventional CPB, this review aims to inform future strategies for haemostasis management in cardiac surgery in a novel cohort of surgical patients. Full article

Background: Little is known about women’s contraceptive use in the United States during the novel coronavirus (“COVID-19”) pandemic and the risk of unintended pregnancy. Methods: We compared the weighted response rates on contraception use for female respondents aged 18–44 from the Behavioral Risk Factor Surveillance System (BRFSS) between 2019 and 2022. Results: Our study reveals a significant increase of 16.1% (CI = 0.145, 0.177) in the proportion of women using contraception in 2022 as compared to 2019. The largest increase in the use of non-reversible contraception was seen in the proportion of female sterilization, at 3.0% (CI = 0.017, 0.043), mostly attributed to non-Hispanic Black individuals with a 12% increase (CI = 0.046, 0.198). The largest decrease was seen in the use of condoms, at 7.4% (CI = −0.094, −0.055). This was driven by both non-Hispanic Black and multiracial groups, each experiencing a 19% decrease (CI = −0.251, −0.127; CI = −0.304, −0.068, respectively). The proportion of women at risk of unintended pregnancy increased by 3.7% (CI = 0.010, 0.063). These increases were observed among those with an income of less than USD 15k, showing a 14.9% increase (CI = 0.037, 0.262). Older females and those with Medicaid insurance were more likely to use female sterilization. Hispanics, college graduates, and those with Medicaid insurance were more likely to use condoms. Non-White females and those without annual checkups were more at risk of unintended pregnancy. Conclusions: Contraceptive methods shifted among females with slightly increased sterilization in the years 2019 to 2022. Full article

Viral zoonoses or viral pathogens transmitted from animals to humans—constitute a rapidly intensifying global health and economic challenge. They are responsible for an estimated 2.5 billion illnesses and 2.7 million deaths annually, representing nearly 60% of all infectious diseases and 75% of newly emerging infections. Recent outbreaks, including Coronavirus disease 2019 (COVID-19), Ebola, Nipah, and avian influenza, underscore their capacity to overwhelm health systems, with COVID-19 alone projected to reduce global Gross Domestic Product by USD 22 trillion by 2025 and impose annual healthcare costs of USD 2–3 trillion. Beyond mortality and morbidity, zoonotic events disrupt trade, depress rural livelihoods, and inflict agricultural losses exceeding USD 100 billion per outbreak, with impacts disproportionately borne by low- and middle-income countries. Hotspot regions across tropical North and South America, Asia, and Central Africa remain especially vulnerable due to accelerating land use change, climate variability, and intensified wildlife–human interfaces. While the Global One Health Index highlights high regional heterogeneity, with sub-Saharan Africa scoring lowest, a critical gap persists between the conceptual strength of One Health and its operationalization in resource-limited settings. This review synthesizes evidence on drivers, clinical manifestations, and socioeconomic burdens of viral zoonoses, while highlighting novel perspectives on equity gaps, co-infection dynamics, and limitations of global preparedness initiatives. We argue that current strategies remain over-reliant on donor-driven agendas and insufficiently integrated across sectors. Addressing future zoonotic threats requires prioritizing surveillance in high-risk geographies, integrating epidemiological and economic data for preparedness planning, and supporting context sensitive One Health approaches that confront political, financial, and structural barriers to implementation. Full article

In order to effectively control the spread of the 2019 novel coronavirus (COVID-19), China has undertaken relatively strict blockade measures, which can effectively reduce population mobility and eliminate transmission pathways at the source. Therefore, it is of great significance to understand the impact of urban blockades on the air quality before, during, and after COVID-19. This study uses data collected from monitoring stations in Xi’an, a typical city in northwestern China, from 2018 to 2023 to conduct an in-depth analysis of the changes in concentration of various pollutants in the atmosphere from a spatiotemporal perspective. The results showed that the average concentrations of particulate matter with aerodynamic diameters less than 2.5 µm (PM_2.5), particulate matter with aerodynamic diameters less than 10 µm (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), ozone (O₃), and carbon monoxide (CO) decreased during the epidemic lockdown (2020–2022) by 18.7%, 15.4%, 29.4%, 20.9%, 0.03%, and 28.1%, respectively. After the implementation of urban lockdown (2023), the annual average concentrations of the five major pollutants other than O₃ decreased, while the concentration of O₃ increased. The monthly changes in concentration of PM_2.5, PM₁₀, CO, SO₂, and NO₂ were similar during 2018–2023, being “higher in winter and lower in summer”. The monthly average concentration of O₃ changed in a “unimodal” manner. The concentrations of SO₂, NO₂, and PM₁₀ decreased the most in January, by 46.4%, 33.5%, and 26.4%, respectively. The concentration of CO decreased the most in April, by 37.3%. PM_2.5 decreased the most in May, with a decrease of 26.7%. O₃ showed the largest increase in November, by 28.6%. After taking relevant measures, the concentrations of various pollutants and their correlations decreased. However, after resuming work, the concentrations of pollutants were still relatively high, and long-term management of air quality in Xi’an is still needed. These results provide a scientific basis for formulating more precise and effective air pollution control strategies. Full article

Background/Objectives: Although the U.S. Food and Drug Administration (FDA) has approved one antiviral treatment and authorized others for emergency use, there is no fully effective antiviral therapy for coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Assays detecting virus-specific immunoglobulins (Ig) or nucleic acids in large-scale epidemiological, vaccine, and drug development studies remain limited due to high costs, reagent accessibility, and cumbersome protocols. Methods: A multiplex bead-based assay was developed to simultaneously detect human IgM, IgG, and IgA antibodies against the SARS-CoV-2 spike receptor binding domain (RBD) in serum using flow cytometry. Assay performance was evaluated for sensitivity, specificity, reproducibility, and cross-reactivity and compared to another immunoassay platform. Results: The assay enabled simultaneous measurement of three antibody isotypes across 624 samples within 2 h. Intra-plate coefficients of variation (CVs) ranged from 3.16 to 6.71%, and inter-plate CVs ranged from 3.33 to 5.49%, demonstrating high reproducibility. The platform also quantified background noise from nonspecific binding, facilitating straightforward data interpretation. Conclusions: This novel, flexible multiplex bead-based assay utilizing a well-established platform provides a rapid and reproducible approach for detecting SARS-CoV-2-specific antibodies. Its high throughput capacity and low variability make it well suited for large-scale epidemiological, vaccine, and therapeutic studies. The platform’s adaptability further supports application to other infectious diseases, offering an ideal tool for broad immunological surveillance. Full article

Novel coronavirus (SARS-CoV-2) is highly infectious and pathogenic. Novel coronavirus infection can not only cause respiratory diseases but also lead to multiple organ damage through direct or indirect mechanisms, in which the liver is one of the most frequently affected organs. It has been reported that 15–65% of coronavirus disease 2019 (COVID-19) patients experience liver dysfunction, mainly manifested as mild to moderate elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Severe patients may progress to liver failure, develop hepatic encephalopathy, or have poor coagulation function. The mechanisms underlying this type of liver injury are complex. Pathways—including direct viral infection (via ACE2 receptors), immune-mediated responses (e.g., cytokine storm), ischemic/hypoxic liver damage, thrombosis, oxidative stress, neutrophil extracellular trap formation (NETosis), and the gut–liver axis—remain largely speculative and lack robust clinical causal evidence. In contrast, drug-induced liver injury (DILI) has been established as a well-defined causative factor using the Roussel Uclaf Causality Assessment Method (RUCAM). Treatment should simultaneously consider antiviral therapy and liver protection therapy. This article systematically reviewed the mechanism, clinical diagnosis, treatment, and management strategies of COVID-19-related liver injury and discussed the limitations of current research and the future directions, hoping to provide help for the diagnosis and treatment of such patients. Full article

Novel therapies to treat infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of respiratory coronavirus disease 2019 (COVID-19), would be of great clinical value to combat the current and future pandemics. Two viral proteases, papain-like protease (PL^pro) and the main protease 3-chymotrypsin-like protease (3CL^pro), are vital in processing the SARS-CoV-2 polyproteins (pp1a and pp1ab) and in releasing 16 nonstructural proteins, making them attractive antiviral drug targets. In this study, we investigated the degradation of the SARS-CoV-2 main protease 3CL^pro by matrix metalloproteinase-14 (MMP14). MMP14 is known to recognize over 10 distinct substrate cleavage sequences. Through sequence analysis, we identified 17 and 10 putative MMP14 cleavage motifs within the SARS-CoV-2 3CL^pro and PL^pro proteases, respectively. Despite the presence of potential sites in both proteins, our in vitro proteolysis assays demonstrated that MMP14 selectively binds to and degrades 3CL^pro, but not PL^pro. This selective proteolysis by MMP14 results in the complete loss of 3CL^pro enzymatic activity. In addition, SARS-CoV-2 pseudovirus replication was inhibited in 293 T cells when either full-length MMP14 or its catalytic domain (cat-MMP14) were overexpressed, presumably due to 3CL^pro degradation by MMP14. Finally, to prevent MMP14 from degrading off-target proteins, we propose a new recombinant pro-PL-MMP14 construct that can be activated only by another SARS-CoV-2 protease, PL^pro. These findings could open the potential of an alternative therapeutic strategy against SARS-CoV-2 infection. Full article

Lower respiratory tract infections (LRTIs) remain a major cause of global morbidity and mortality, yet accurate pathogen identification and risk stratification continue to pose clinical challenges. Lipidomics—the comprehensive analysis of lipid species within biological systems—has emerged as a promising tool to unravel host–pathogen interactions and reveal novel diagnostic and prognostic biomarkers. This systematic review synthesizes evidence from nine original studies applying mass spectrometry-based lipidomic profiling in human LRTIs, including community-acquired pneumonia (CAP), ventilator-associated pneumonia (VAP), and coronavirus disease 2019 (COVID-19). Across diverse study designs, sample types, and analytical platforms, consistent alterations in lipid metabolism were observed. Perturbations in phospholipid classes, particularly phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs), were frequently associated with disease severity and immune activation. The ratios of PC to LPC and phosphatidylethanolamine (PE) to lysophosphatidylethanolamine (LPE) emerged as markers of inflammatory remodeling. Sphingolipids—including sphingomyelins (SMs) and sphingosine-1-phosphate (S1P)—were identified as key modulators of monocyte and neutrophil activation. Fatty acid–derived lipid mediators such as oxylipins (e.g., 12,13-epoxyoctadecenoic acid and 15-hydroxyeicosatetraenoic acid) and acylcarnitines reflected pathogen-specific immune responses and mitochondrial dysfunction. Several lipid-based classifiers demonstrated superior diagnostic and prognostic performance compared to conventional clinical scores, including the CURB-65 and pneumonia severity index. However, significant heterogeneity in experimental design, lipid identification workflows, and reporting standards limits inter-study comparability. While preliminary findings support the integration of lipidomics into infectious disease research, larger multi-omic and longitudinal studies are required. This review provides the first comprehensive synthesis of lipidomic alterations in human LRTIs and highlights their emerging translational relevance. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized by pattern recognition receptors (PRRs), which play a vital role in triggering innate immune responses such as the production of type I and III interferons (IFNs). While modest PRR activation helps to defend against SARS-CoV-2, excessive or sustained activation can cause harmful inflammation and contribute to severe Coronavirus Disease 2019 (COVID-19). Altered expression of Toll-like receptors (TLRs), which are among the most important members of the PRR family members, particularly TLRs 2, 3, 4, 7, 8 and 9, has been strongly linked to COVID-19 severity. Furthermore, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), collectively known as RLRs (RIG-I-like receptors), act as sensors that detect SARS-CoV-2 RNA. The expression of these receptors, as well as that of different DNA sensors, varies in patients infected with SARS-CoV-2. Changes in PRR expression, particularly that of TLRs, cyclic GMP-AMP synthase (cGAS), and the stimulator of interferon genes (STING), have also been shown to play a role in the development and persistence of long COVID (LC). However, SARS-CoV-2 has evolved strategies to evade PRR recognition and subsequent signaling pathway activation, contributing to the IFN response dysregulation observed in SARS-CoV-2-infected patients. Nevertheless, PRR agonists and antagonists remain promising therapeutic targets for SARS-CoV-2 infection. This review aims to describe the PRRs involved in recognizing SARS-CoV-2, explore their expression during SARS-CoV-2 infection, and examine their role in determining the severity of both COVID-19 and long-term manifestations of the disease. It also describes the strategies developed by SARS-CoV-2 to evade PRR recognition and activation. Moreover, given the considerable interest in modulating PRR activity as a novel immunotherapy approach, this review will provide a description of PRR agonists and antagonists that have been investigated as antiviral strategies against SARS-CoV-2. This review aims to explore the complex interplay between PRRs and SARS-CoV-2 in depth, considering its implications for prognostic biomarkers, targeted therapeutic strategies and the mechanistic understanding of long LC. Additionally, it outlines future perspectives that could help to address knowledge gaps in PRR-mediated responses during SARS-CoV-2 infection. Full article

Luteolin is a natural flavonoid compound with multifaceted pharmacological properties, including anti-oxidant, anti-inflammatory, antiviral, and anti-tumor activities. Network pharmacology analysis has been utilized to decipher the underlying mechanisms and multitargets of luteolin against coronavirus disease 2019 (COVID-19). This review aims to provide a systematic and comprehensive summary of luteolin, as a potential novel remedy with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity, as well as its anti-oxidant mechanisms. We systematically delineate the epidemiological profile, genomic architecture, and replicative dynamics of SARS-CoV-2, thereby constructing a multiscale framework to decode its pathogenic mechanisms. Employing a multi-level network pharmacology analytical strategy, we identify 46 core targets through protein interaction network construction, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Molecular investigations reveal luteolin’s dual antiviral mechanisms, including direct targeting of SARS-CoV-2 proteins and host-directed intervention through suppression of angiotensin-converting enzyme 2 receptor engagement/transmembrane protease serine 2-mediated viral priming. The polypharmacological profile of luteolin demonstrates synergistic effects in blocking viral entry, replication, and host inflammatory cascades. This phytochemical repurposing study of luteolin provides a novel mechanistic paradigm for developing multitarget antiviral agents, highlighting the translational value of natural compounds in combating emerging viral variants. 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

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