The role of oxidative stress in the pathogenesis of infections with coronaviruses

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 13, 2023

Coronaviruses can cause serious respiratory tract infections and may also impact other end organs such as the central nervous system, lung heart. The coronavirus disease 2019 (COVID-19) has had a devastating on humanity. Understanding mechanisms that contribute to pathogenesis of infections, will set foundation for development new treatments attenuate with coronaviruses host cells tissues. During infection cells, trigger an imbalance between increased production reactive oxygen species (ROS) reduced antioxidant responses leads redox stress. Subsequently, stress contributes antiviral virus-induced inflammation apoptosis ultimately drive cell tissue damage organ disease. However, there is limited understanding how different including SARS-CoV-2, manipulate cellular machinery drives responses. This review aims elucidate involved in replication associated inflammation, apoptotic pathways, autoimmunity, vascular dysfunction collectively multiorgan damage.

Language: Английский

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Long-Term Sequelae of COVID-19 in Experimental Mice

Molecular Neurobiology, Journal Year: 2022, Volume and Issue: 59(10), P. 5970 - 5986

Published: July 13, 2022

Abstract We recently reported acute COVID-19 symptoms, clinical status, weight loss, multi-organ pathological changes, and animal death in a murine hepatitis virus-1 (MHV-1) coronavirus mouse model of COVID-19, which were similar to that observed humans with COVID-19. further examined long-term (12 months post-infection) sequelae these mice. Congested blood vessels, perivascular cavitation, pericellular halos, vacuolation neuropils, pyknotic nuclei, eosinophilic necrosis, necrotic neurons fragmented the brain cortex 12 post-MHV-1 infection. These changes associated increased reactive astrocytes microglia, hyperphosphorylated TDP-43 tau, decrease synaptic protein synaptophysin-1, suggesting possible impact SARS-CoV-2 infection on defective neuronal integrity. The lungs showed severe inflammation, bronchiolar airway wall thickening due fibrotic remodeling, bronchioles numbers goblet cells epithelial lining, bronchiole walls inflammatory cells. Hearts interstitial edema, vascular congestion dilation, nucleated red (RBCs), RBCs infiltrating between degenerative myocardial fibers, apoptotic bodies myocyte hypertrophy, fibrosis. Long-term liver kidney less than those phase. Noteworthy, treatment infected mice small molecule synthetic peptide prevents binding spike its respective receptors significantly attenuated disease progression, as well post-long-term Collectively, findings suggest may result long-term, irreversible predominantly brain, lung, heart.

Language: Английский

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Kidney Damage in Long COVID: Studies in Experimental Mice

Biology, Journal Year: 2023, Volume and Issue: 12(8), P. 1070 - 1070

Published: July 30, 2023

Signs and symptoms involving multiple organ systems which persist for weeks or months to years after the initial SARS-CoV-2 infection (also known as PASC long COVID) are common complications of individuals with COVID-19. We recently reported pathophysiological changes in various organs post-acute mice mouse hepatitis virus-1 (MHV-1, a coronavirus) (7 days) long-term post-infection (12 months). One severely affected this animal model is kidney, correlated well human studies showing kidney injury post-SARS-CoV-2 infection. Our pathological observation kidneys includes development edema inflammation renal parenchyma, severe acute tubular necrosis, infiltration macrophages lymphocytes, addition observed both post-infection, include epithelial cell degenerative changes, peritubular vessel congestion, proximal distal hemorrhage interstitial tissue, vacuolation tubules. These findings strongly suggest possible fibrosis, particular post-infection. Accordingly, we investigated whether signaling system that initiate above-mentioned other conditions also activated post-MHV-1 found increased TGF-β1, FGF23, NGAL, IL-18, HIF1-α, TLR2, YKL-40, B2M mRNA levels infection, but not EGFR, TNFR1, BCL3, WFDC2. However, only neutrophil gelatinase-associated lipocalin (NGAL) days). Immunoblot showed an elevation protein TLR-2, EGFR while KIM-1 MMP-7 Treatment synthetic peptide, SPIKENET (SPK), inhibits spike binding, reduced NGAL decreased BCL3 mRNA, TLR-2 fibrotic events may early leading pronounced fibrosis COVID. Targeting these factors therapeutically prevent long-COVID-associated complications.

Language: Английский

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Dermatologic Changes in Experimental Model of Long COVID

Microorganisms, Journal Year: 2024, Volume and Issue: 12(2), P. 272 - 272

Published: Jan. 27, 2024

The coronavirus disease-19 (COVID-19) pandemic, declared in early 2020, has left an indelible mark on global health, with over 7.0 million deaths and persistent challenges. While the pharmaceutical industry raced to develop vaccines, emergence of mutant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains continues pose a significant threat. Beyond immediate concerns, long-term health repercussions COVID-19 survivors are garnering attention, particularly due documented cases cardiovascular issues, liver dysfunction, pulmonary complications, kidney impairments, notable neurocognitive deficits. Recent studies have delved into pathophysiological changes various organs following post-acute infection murine hepatitis virus-1 (MHV-1), coronavirus, mice. One aspect that stands out is impact skin, previously underexplored facet effects. research reveals cutaneous findings during both phases post-MHV-1 infection, mirroring certain alterations observed humans post-SARS-CoV-2 infection. In stages, mice exhibited destruction epidermal layer, increased hair follicles, extensive collagen deposition dermal hyperplasticity sebaceous glands. Moreover, thinning panniculus carnosus adventitial layer was noted, consistent human studies. A investigation revealed absence adipose tissues, further damage layer. Remarkably, treatment synthetic peptide, SPIKENET (SPK), designed prevent Spike glycoprotein-1 binding host receptors elicit potent anti-inflammatory response, showed protection against MHV-1 Precisely, SPK restored follicle loss re-architected layers, successfully overhauled fatty tissue destruction. These promising underscore potential as therapeutic intervention skin initiated by SARS-CoV-2, providing glimmer hope battle lingering effects pandemic.

Language: Английский

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The Impact of SARS-CoV-2 Infection on Heart Rate Variability: A Systematic Review of Observational Studies with Control Groups

International Journal of Environmental Research and Public Health, Journal Year: 2023, Volume and Issue: 20(2), P. 909 - 909

Published: Jan. 4, 2023

Autonomic nervous system (ANS) dysfunction can arise after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and heart rate variability (HRV) tests assess its integrity. This review investigated the relationship between impact of SARS-CoV-2 on HRV parameters. Comprehensive searches were conducted in four electronic databases. Observational studies with a control group reporting direct parameters July 2022 included. A total 17 observational included this review. The square root mean squared differences successive NN intervals (RMSSD) was most frequently investigated. Some found that decreases RMSSD high frequency (HF) power associated or poor prognosis COVID-19. Also, increases normalized unit HF related to death critically ill COVID-19 patients. findings showed infection, severity COVID-19, are likely be reflected some HRV-related However, considerable heterogeneity highlighted. methodological quality not optimal. suggest rigorous accurate measurements highly needed topic.

Language: Английский

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Genetics of Long COVID: Exploring the Molecular Drivers of Persistent Pulmonary Vascular Disease Symptoms

Infectious Disease Reports, Journal Year: 2025, Volume and Issue: 17(1), P. 15 - 15

Published: Feb. 13, 2025

Background/ Objectives: Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC) are symptoms that manifest despite passing the acute phase. These manifestations encompass a wide range symptoms, most common being fatigue, shortness breath, and cognitive dysfunction. Genetic predisposition is clearly involved in susceptibility individuals to developing these persistent variation severity forms. This review summarizes role genetic factors gene polymorphisms development major pulmonary vascular disorders associated with long COVID. Methods: A comprehensive current literature was conducted examine contributions complications following infection. Studies investigating linked hypertension, thromboembolism, endothelialitis were reviewed summarized. Results: Findings show specific variants contribute increased patients. Variants endothelial dysfunction, coagulation pathways, inflammatory responses have been implicated hypertension thromboembolic events. predispositions influencing integrity immune appear influence disease progression. Conclusions: Understanding mechanisms could pave way for targeted therapeutic interventions alleviate burden on patients experiencing

Language: Английский

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A Mouse Model of MHV‐1 Virus Infection for Study of Acute and Long COVID Infection

Current Protocols, Journal Year: 2023, Volume and Issue: 3(10)

Published: Oct. 1, 2023

COVID-19, caused by SARS-CoV-2, has had a significant global impact. While vaccines and treatments have reduced severe cases deaths, the long-term effects are not yet well understood. Current models used for research, such as non-human primates transgenic mice, expensive require scarce Biosafety Level-3 (BSL-3) laboratories, thereby limiting their practicality. However, mouse hepatitis virus 1 (MHV-1) model offers promising alternative. This surrogate can be investigated in more widely available Level-2 (BSL-2) laboratories. Furthermore, mice affordable easy to handle, utilizing MHV-1 SARS-CoV-2 eliminates need costly mice. Importantly, successfully recapitulates COVID-19-related clinical symptoms, weight loss, multiorgan pathological changes failure acute stages, irreversible neurological complications, other organ dysfunction post-infection, which similar human data post-COVID-19. To assist researchers establishing using model, this protocol comprehensive guidance encompassing procedures animal preparation, induction of viral infection, observation, changes, tissue analysis mechanistic studies, yielding valuable insights into disease mechanisms progression. By adopting provided protocols, effectively circumvent financial constraints limited availability BSL-3 thus facilitating accessible cost-effective approach investigating underlying pathophysiology exploring potential therapeutic interventions. © 2023 Wiley Periodicals LLC. Basic Protocol: Induction infection A/J Support Protocol 1: Histological evaluation 2: Liver enzyme measurement 3: Western blot aquaporin expression 4: mRNA 5: Immunohistochemistry/immunofluorescence 6: Tissue water measurement.

Language: Английский

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The Dark Side of Nosocomial Infections in Critically Ill COVID-19 Patients

Life, Journal Year: 2023, Volume and Issue: 13(6), P. 1408 - 1408

Published: June 17, 2023

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by Severe Acute Respiratory Syndrome 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 global pandemic, virus has spread to more than 200 countries with 500 million cases and 6 deaths reported globally. It long been known that viral tract infections predispose patients bacterial these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also as healthcare-associated (HAIs), are those absent at time of admission acquired after hospitalization. However, impact coinfections or secondary on progression its lethal outcome still debated. The aim this review was assess literature incidence superinfections in COVID-19. highlights importance rational use antibiotics need implement antimicrobial stewardship principles prevent transmission drug-resistant organisms healthcare settings. Finally, alternative agents counter emergence multidrug-resistant bacteria causing will be discussed.

Language: Английский

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The Effect of COVID-19 on Gut Microbiota: Exploring the Complex Interplay and Implications for Human Health

Gastrointestinal Disorders, Journal Year: 2023, Volume and Issue: 5(3), P. 340 - 355

Published: Aug. 18, 2023

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to significant global health implications. Although respiratory manifestations of are widely recognized, emerging evidence suggests that disease may also significantly affect gut microbiota, intricate community bacteria lives within gastrointestinal system. This extensive article intends investigate impact on examining underlying mechanisms, clinical implications, and potential therapeutic interventions. Understanding complex interactions between microbiota will help us gain valuable insights into broader consequences this viral infection human health.

Language: Английский

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Acute Kidney Injury (AKI) in COVID-19: In silico Identification of LncRNA-MiRNA-Gene Networks and Key Transcription Factors

Current Pharmaceutical Design, Journal Year: 2023, Volume and Issue: 29(24), P. 1907 - 1917

Published: Aug. 16, 2023

Purpose: Acute kidney injury (AKI) accounts for up to 29% of severe COVID-19 cases and increases mortality among these patients. Viral infections participate in the pathogenesis diseases by changing expression profile normal transcriptome. This study attempts identify LncRNA-miRNA-gene TF-gene networks as gene regulating tissues Methods: In this analysis, four libraries from GEO repository were considered. To conduct preprocessing, Deseq2 software R was used purpose data normalization log2 transformation. addition, pre- post-normalization, PCA box plots developed using ggplot2 quality control. The profiles samples patients control individuals compared DEseq2 R. considered significance thresholds DEGs Adj P value < 0.05 |logFC| >2. Then, predict molecular interactions lncRNA-miRNA-gene networks, different databases, including DeepBase v3.0, miRNATissueAtlas2, DIANA-LncBase v3, miRWalk, used. Furthermore, employing ChEA at TF-Gene level obtained. Finally, obtained plotted Stringdb Cytoscape v8. Results: Results comparison post-mortem tissue with healthy showed significant changes more than 2000 genes. predictions regarding miRNA-gene interaction network based on meta-analysis that 11 miRNAs targeted DEGs. Interestingly, tissue, interacted LINC01874, LINC01788, LINC01320, which have high specificity tissue. Moreover, transcription factors EGR1, SMAD4, STAT3, CHD1 identified key Taken together, current several dysregulated genes affected COVID-19. Conclusion: suggests TFs new diagnostic therapeutic targets experimental preclinical studies.

Language: Английский

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