Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 816 - 816

Published: March 6, 2023

The development of long-term symptoms coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed "long COVID" or post-acute sequela COVID-19 (PASC), can implicate persistent neurological complications in up to one third patients and present as fatigue, "brain fog", headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, peripheral neuropathy. Pathogenic mechanisms these long COVID remain largely unclear; however, several hypotheses both nervous system systemic pathogenic such SARS-CoV2 viral persistence neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, endotheliopathy. Outside the CNS, SARS-CoV-2 invade support stem cells olfactory epithelium leading alterations function. infection may induce abnormalities innate adaptive immunity including monocyte expansion, T-cell exhaustion, prolonged cytokine release, which cause neuroinflammatory responses microglia activation, white matter abnormalities, microvascular changes. Additionally, clot formation occlude capillaries endotheliopathy, due protease activity complement contribute hypoxic neuronal injury blood-brain barrier dysfunction, respectively. Current therapeutics target pathological by employing antivirals, decreasing inflammation, promoting regeneration. Thus, from laboratory evidence clinical trials literature, we sought synthesize pathophysiological pathways underlying potential therapeutics.

Language: Английский

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Long Covid: where we stand and challenges ahead

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 7, 2022

Abstract Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially Long Covid, has been defined a constellation signs symptoms which persist for weeks or months after the initial infection. PASC affects wide range diverse organs systems, with manifestations involving lungs, brain, cardiovascular system other such kidney neuromuscular system. The pathogenesis is complex multifactorial. Evidence suggests that seeding persistence in different organs, reactivation, response to unrelated viruses EBV, autoimmunity, uncontrolled inflammation are major drivers PASC. relative importance pathogenetic pathways may differ tissue organ contexts. vaccination, addition protecting against disease, reduces breakthrough infection although its actual impact remains be defined. represents formidable challenge health care systems dissecting mechanisms pave way targeted preventive therapeutic approaches.

Language: Английский

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Innate metabolic responses against viral infections

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(10), P. 1245 - 1259

Published: Oct. 20, 2022

Language: Английский

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Risk of incident diabetes after COVID-19 infection: A systematic review and meta-analysis

Metabolism, Journal Year: 2022, Volume and Issue: 137, P. 155330 - 155330

Published: Oct. 8, 2022

Language: Английский

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Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10458 - 10458

Published: June 21, 2023

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; chronic, low-grade inflammatory response; immune dysregulation defective reactivation latent viruses; autoimmunity; persistent endothelial dysfunction coagulopathy; gut dysbiosis; hormonal metabolic dysregulation; mitochondrial dysfunction; autonomic nervous system dysfunction. There are no specific tests for diagnosis LC, clinical features laboratory findings biomarkers not specifically relate to LC. Therefore, is paramount importance develop validate that can employed prediction, prognosis its therapeutic response, although this effort hampered challenges pertaining non-specific nature majority manifestations in spectrum, small sample sizes relevant studies other methodological issues. Promising candidate found some patients markers systemic inflammation, acute phase proteins, cytokines chemokines; reflecting persistence, herpesviruses endotheliopathy, coagulation fibrinolysis; microbiota alterations; diverse proteins metabolites; biomarkers; cerebrospinal fluid biomarkers. At present, there only two reviews summarizing they do cover entire umbrella current biomarkers, their link etiopathogenetic mechanisms or diagnostic work-up comprehensive manner. Herein, we aim appraise synopsize available evidence on typical classification based pathogenetic main symptomatology frame epidemiological aspects syndrome furthermore assess limitations as well potential implications interventions.

Language: Английский

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Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 9, 2023

Background Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity clinical symptoms potential biomarkers for disease 2019 (COVID-19). Several studies described the role small as well complex molecules such metabolites, cytokines, chemokines lipoproteins during in recovered patients. In fact, after SARS-CoV-2 viral almost 10-20% experience persistent post 12 weeks recovery defined long-term COVID-19 (LTCS) or long post-acute (PACS). Emerging evidence revealed that dysregulated immune system persisting inflammation could be one key drivers LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, clear understanding parameters within integrated fashion predict course would help to stratify LTCS This even allow elucidation mechanistic course. Methods study comprised subjects (n=7; longitudinal), (n=33), Recov (n=12), no history positive testing (n=73). 1 H-NMR-based metabolomics IVDr standard operating procedures verified phenotyped all blood samples by quantifying 38 metabolites 112 lipoprotein properties. Univariate multivariate statistics identified NMR-based cytokine changes. Results Here, we report on analysis serum/plasma NMR spectroscopy flow cytometry-based cytokines/chemokines quantification We lactate pyruvate were significantly different either healthy controls (HC) Subsequently, correlation group only among cytokines amino acids histidine glutamine uniquely attributed mainly pro-inflammatory cytokines. Of note, triglycerides several (apolipoproteins Apo-A1 A2) demonstrate COVID-19-like alterations compared HC. Interestingly, distinguished mostly their phenylalanine, 3-hydroxybutyrate (3-HB) glucose concentrations, illustrating imbalanced energy metabolism. Most present at low levels HC except IL-18 chemokine, which tended higher Conclusion The identification plasma will better other diseases ongoing severity

Language: Английский

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Chronic inflammation in post-acute sequelae of COVID-19 modulates gut microbiome: a review of literature on COVID-19 sequelae and gut dysbiosis

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 23, 2025

Language: Английский

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The SARS-CoV-2 spike protein induces long-term transcriptional perturbations of mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in obese mice

Molecular Metabolism, Journal Year: 2023, Volume and Issue: 74, P. 101756 - 101756

Published: June 20, 2023

As the pandemic evolves, post-acute sequelae of CoV-2 (PASC) including cardiovascular manifestations have emerged as a new health threat. This study aims to whether Spike protein plus obesity can exacerbate PASC-related cardiomyopathy.A protein-pseudotyped (Spp) virus with proper surface tropism SARS-CoV-2 was developed for viral entry assay in vitro and administration into high fat diet (HFD)-fed mice. The systemic loads cardiac transcriptomes were analyzed at 2 24 h, 3, 6, weeks post introducing (wpi) Spp using RNA-seq or real time RT-PCR. Echocardiography used monitor functions.Low-density lipoprotein cholesterol enhanced uptake endothelial cells, macrophages, cardiomyocyte-like H9C2 cells. Selective adipose depositions observed HFD mice but not normal-chow-fed transcriptional signatures wpi showed suppression mitochondria respiratory chain genes ATP synthases nicotinamide adenine dinucleotide:ubiquinone oxidoreductase gene members, upregulation stress pathway-related crucial factors such nuclear factor-erythroid 2-related factor 1 signal transducer activator transcription 5A, increases expression glucose metabolism-associated genes. compared age-matched control mice, ejection fraction fractional shortening significantly decreased, while left ventricular end-systolic diameter volume elevated, fibrosis increased wpi.Our data demonstrated that could induce long-term metabolic cause myocardial contractile impairment obese providing mechanistic insights cardiomyopathy.

Language: Английский

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Genetic risk factors for severe and fatigue dominant long COVID and commonalities with ME/CFS identified by combinatorial analysis

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 1, 2023

Long COVID is a debilitating chronic condition that has affected over 100 million people globally. It characterized by diverse array of symptoms, including fatigue, cognitive dysfunction and respiratory problems. Studies have so far largely failed to identify genetic associations, the mechanisms behind disease, or any common pathophysiology with other conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present similar symptoms.We used combinatorial analysis approach combinations variants significantly associated development long examine biological underpinning its various symptoms. We compared two subpopulations patients from Sano Genetics' GOLD study cohort, focusing on severe dominant phenotypes. evaluated signatures previously identified in an ME/CFS population against this understand similarities disorders may be triggered prior viral infection. Finally, we also output known associations diseases, range metabolic neurological disorders, overlap pathophysiological mechanisms.Combinatorial 73 genes were highly at least one populations included analysis. Of these, 9 acute COVID-19, 14 differentially expressed transcriptomic patients. A pathway enrichment revealed pathways most mainly aligned cardiometabolic diseases. Expanded genotype suggests specific SNX9 genotypes are significant contributor risk protection infection, but gene-disease relationship context dependent mediated interactions KLF15 RYR3. Comparison uniquely Severe Fatigue Dominant differences between enriched each subgroup. The unique immune myeloid differentiation macrophage foam cells. Genes subgroup MAPK/JNK signaling. ME/CFS, several involved circadian rhythm regulation insulin regulation. Overall, 39 SNPs can linked recent patient UK Biobank. Among COVID, 42 potentially tractable for novel drug discovery approaches, 13 these already targeted drugs clinical pipelines. From example, TLR4 antagonists repurposing candidates potential protect term impairment pathology caused SARS-CoV-2. currently evaluating targets use treating and/or ME/CFS.This demonstrates power analytics stratifying heterogeneous complex diseases do not simple monogenic etiologies. These results build upon findings analyses COVID-19 expect access additional independent, larger datasets will further improve disease insights validate treatment options COVID.

Language: Английский

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Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection

Matrix Biology, Journal Year: 2023, Volume and Issue: 116, P. 49 - 66

Published: Feb. 1, 2023

Language: Английский

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