Epigenetic patterns, accelerated biological aging, and enhanced epigenetic drift detected 6 months following COVID-19 infection: insights from a genome-wide DNA methylation study

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Aug. 20, 2024

The epigenetic status of patients 6-month post-COVID-19 infection remains largely unexplored. existence long-COVID, or post-acute sequelae SARS-CoV-2 (PASC), suggests potential long-term changes. Long-COVID includes symptoms like fatigue, neurological issues, and organ-related problems, regardless initial severity. mechanisms behind long-COVID are unclear, but virus-induced changes could play a role. Our study explores the lasting impacts infection. We analyzed genome-wide DNA methylation patterns in an Italian cohort 96 6 months after COVID-19 exposure, comparing them to 191 healthy controls. identified 42 CpG sites with significant differences (FDR < 0.05), primarily within islands gene promoters. Dysregulated genes highlighted links glutamate/glutamine metabolism, which may be relevant PASC symptoms. Key significance effects include GLUD1, ATP1A3, ARRB2. Furthermore, Horvath's clock showed slight age acceleration patients. also observed substantial increase stochastic mutations (SEMs) group, implying drift. SEM analysis 790 affected genes, indicating dysregulation pathways related insulin resistance, VEGF signaling, apoptosis, hypoxia response, T-cell activation, endothelin signaling. provides valuable insights into consequences COVID-19. Results suggest possible associations accelerated aging, drift, disruption critical biological linked immune vascular health. Understanding these crucial for elucidating complex developing targeted therapeutic interventions.

Language: Английский

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The Role of Inflammation in the Pathogenesis of Viral Respiratory Infections

Microorganisms, Journal Year: 2024, Volume and Issue: 12(12), P. 2526 - 2526

Published: Dec. 7, 2024

Viral respiratory infections (VRIs) are a leading cause of morbidity and mortality worldwide, making them significant public health concern. During infection, viruses, including Influenza virus, SARS-CoV-2, syncytial virus (RSV), trigger an antiviral immune response, specifically boosting the inflammatory response that plays critical role in their pathogenesis. The induced by viruses can be double-edged sword since it initially to protective/reparative from virus-induced injuries. Still, also detrimental host cells tissues. However, mechanisms differentiate complex crosstalk between favorable responses harmful poorly understood. This review explores interplay viral pathogens mainly focusing on inflammation pathogenesis VRIs. We discuss how both contain exacerbate progression infections, highlighting potential therapeutic targets emerging drugs for modulating aberrant during

Language: Английский

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The roles of cellular protease interactions in viral infections and programmed cell death: a lesson learned from the SARS-CoV-2 outbreak and COVID-19 pandemic

Pharmacological Reports, Journal Year: 2022, Volume and Issue: 74(6), P. 1149 - 1165

Published: Aug. 23, 2022

Abstract The unprecedented pandemic of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to COVID-19, is threatening global health. Over the last 2 years, we have witnessed rapid progress in research focusing on developing new antiviral vaccines and drugs, as well academic clinical efforts understand biology pathology COVID-19. roles proteases among master regulators invasion replication their pivotal host defence against this pathogen, including programmed cell death, not been established. Our understanding protease function health disease has increased considerably over two decades, with caspases, matrix metalloproteases, transmembrane serine representing most prominent examples. Therefore, during COVID-19 pandemic, these enzymes investigated potential molecular targets for therapeutic interventions. Proteases that are responsible entry replication, such TMPRSS2, ACE2 or cathepsins, screened inhibitor libraries discover lead structures further drug design would prevent virus multiplication. On other hand, orchestrate death can also be harnessed enhance desired demise infected cells through apoptosis attenuate highly inflammatory lytic undesired cytokine storms, a major hallmark severe Given role SARS-CoV-2-induced discuss individual catalytic interactions article. We provide rationale targeting participating treatments identify knowledge gaps might better mechanism underlying death.

Language: Английский

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Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice

Frontiers in Bioscience-Landmark, Journal Year: 2022, Volume and Issue: 27(11), P. 316 - 316

Published: Nov. 30, 2022

Background: The recently emerged variants of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pose a threat to public health. Understanding pathogenicity these is salient factor in development effective SARS-CoV-2 therapeutics. This study aimed compare expression patterns genes involved immune responses K18-hACE2 mice infected with wild-type, Delta, and Omicron variants. Methods: were intranasally either wild-type (B.1), Delta (B.1.617.2), or (B.1.1.529) On day 6 post-infection, lung, brain, kidney tissues collected from each variant-infected group. mRNA levels 39 response all three groups compared by RT-qPCR. Viral titers measured using median tissue culture infectious dose (TCID50) assay expressed as Log10 TCID50/0.1 g. statistical significance differences gene was determined one-way analysis variance (ANOVA) (alpha = 0.05). Results: toll-like receptors (TLRs) upregulated lung brain wild-type- Delta-infected but not those Omicron-infected highest cytokines, including interleukin (IL)-1α, IL-1β, IL-17α, interferon, tumor necrosis factors, observed lungs variant. Additionally, CCL4, CCL11, CXCL9, CXCL10 (>3-fold) wild-type-infected mice, markedly higher expressions than lungs. Most apoptotic factors mainly (caspase 8, caspase 9, p53, Bax, Bak, BCL-2, Bcl-XL), whereas neither nor showed more 3-fold upregulation factors. Conclusions: Collectively, our findings revealed that variant exhibited pathogenicity, followed variant, then

Language: Английский

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Significance of Catecholamine Biosynthetic/Metabolic Pathway in SARS-CoV-2 Infection and COVID-19 Severity

Cells, Journal Year: 2022, Volume and Issue: 12(1), P. 12 - 12

Published: Dec. 20, 2022

The SARS-CoV-2 infection was previously associated with the expression of dopamine biosynthetic enzyme L-Dopa decarboxylase (DDC). Specifically, a negative correlation detected between DDC mRNA and RNA levels in vitro infected epithelial cells nasopharyngeal tissue COVID-19 patients mild/no symptoms. However, DDC, among other genes related to both SARS-CoV-2-infection (ACE2, dACE2, EPO), upregulated these patients, possibly attributed an orchestrated host antiviral response. Herein, by comparing swab samples severe/critical mild cases, we showed 20 mean-fold reduction, highlighting importance this gene as potential marker severity. Moreover, identified association key catecholamine biosynthesis/metabolism-related genes, whole blood from hospitalized cultured cells. viral downregulated part pathway (reduction up 7.5 mean-fold), while enhanced catabolizing (increase monoamine oxidases A B 15 10 mean-fold, respectively) vivo, irrespectively presence comorbidities. In accordance, sera severe cases were reduced (up 3.8 mean-fold). Additionally, moderate positive MAOA (r = 0.527, p < 00001) upon SARS-CoV-2-infection. These observations consistent data SARS-CoV-2-infected Vero E6 A549 Furthermore, or treatment attenuated virus-derived cytopathic effect 55% 59%, respectively. mediated suppression biosynthesis cell culture was, at least part, hypoxia-like conditions triggered infection. findings suggest that L-Dopa/dopamine intake may have preventive therapeutic value for patients.

Language: Английский

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