Blood DNA methylation and COVID-19 outcomes

Clinical Epigenetics, Год журнала: 2021, Номер 13(1)

Опубликована: Май 25, 2021

There are no prior reports that compare differentially methylated regions of DNA in blood samples from COVID-19 patients to collected before the SARS-CoV-2 pandemic using a shared epigenotyping platform. We performed genome-wide analysis circulating CpG methylation Infinium Human MethylationEPIC BeadChip on 124 hospitalized COVID-19-positive and COVID-19-negative compared these data with previously reported 39 healthy individuals pandemic. Prospective outcome measures such as COVID-19-GRAM risk-score mortality were combined data.Global mean levels did not differ between pre-pandemic controls. About 75% acute illness-associated located near gene promoter hypo-methylated comparison Gene ontology analyses revealed terms associated immune response viral infections leukocyte activation; disease predominance autoimmune disorders. Among patients, worse outcomes prevailing hyper-methylated status. Recursive feature elimination identified 77 positions predictive severity measured by GRAM-risk score.Our contribute awareness may influence expression genes regulate progression represent targetable process setting.

Язык: Английский

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A review of cytokine-based pathophysiology of Long COVID symptoms

Frontiers in Medicine, Год журнала: 2023, Номер 10

Опубликована: Март 31, 2023

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase illness, in whom recovery is prolonged, or new are developed over months. Here, we propose a description pathophysiology COVID presentation based on inflammatory cytokine cascades and p38 MAP kinase signaling pathways that regulate production. In this model, SARS-CoV-2 viral infection hypothesized to trigger dysregulated peripheral immune system activation subsequent release. Chronic low-grade inflammation leads brain microglia an exaggerated release central cytokines, producing neuroinflammation. Immunothrombosis linked chronic microclot formation decreased tissue perfusion ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS "brain fog," arthralgias, paresthesias, dysautonomia, GI ophthalmic problems can consequently arise as result elevated cytokines. There abundant similarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms viral-induced epigenetic changes gene expression may lead patients, predisposing some develop autoimmunity, which be gateway ME/CFS.

Язык: Английский

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Therapeutic targets and interventional strategies in COVID-19: mechanisms and clinical studies

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Авг. 26, 2021

Abstract Owing to the limitations of present efforts on drug discovery against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and lack understanding biological regulation mechanisms underlying COVID-19, alternative or novel therapeutic targets for COVID-19 treatment are still urgently required. SARS-CoV-2 infection immunity dysfunction two main courses driving pathogenesis COVID-19. Both virus host factors potential antiviral therapy. Hence, in this study, current strategies have been classified into “target virus” host” categories. Repurposing drugs, emerging approaches, promising implementations above strategies. First, a comprehensive review highly acclaimed old drugs was performed according evidence-based medicine provide recommendations clinicians. Additionally, their unavailability fight analyzed. Next, profound analysis approaches conducted, particularly all licensed vaccines monoclonal antibodies (mAbs) enrolled clinical trials primary mutant strains. Furthermore, pros cons were compared from different perspectives. Finally, most reviewed, update progress treatments has summarized based these reviews.

Язык: Английский

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The epigenetic implication in coronavirus infection and therapy

Clinical Epigenetics, Год журнала: 2020, Номер 12(1)

Опубликована: Окт. 21, 2020

Abstract Epigenetics is a relatively new field of science that studies the genetic and non-genetic aspects related to heritable phenotypic changes, frequently caused by environmental metabolic factors. In host, epigenetic machinery can regulate gene expression through series reversible modifications, such as histone methylation acetylation, DNA/RNA methylation, chromatin remodeling, non-coding RNAs. The coronavirus disease 19 (COVID-19) highly transmittable pathogenic viral infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China, spread worldwide, causes it. COVID-19 severity consequences largely depend on patient age health status. this review, we will summarize comparatively analyze how viruses host epigenome. Mainly, be focusing respiratory RNA virus infections coronaviruses. context, alterations might play an essential role onset complications. Although many therapeutic approaches are under study, more research urgently needed identify effective vaccine or safer chemotherapeutic drugs, including cope with outbreak develop pre- post-exposure prophylaxis against COVID-19.

Язык: Английский

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Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: a global perspective

Nature Reviews Cardiology, Год журнала: 2021, Номер 19(5), С. 314 - 331

Опубликована: Дек. 6, 2021

The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with hypoxia being cause death in most critical cases. Coronavirus disease 2019 (COVID-19) is extremely heterogeneous terms severity, clinical phenotype and, importantly, global distribution. Although majority affected patients recover from many continue to suffer late sequelae affecting various organs, including lungs. role pulmonary vascular system during and chronic stages COVID-19 has not been adequately studied. A thorough understanding origins dynamic behaviour SARS-CoV-2 virus potential causes heterogeneity essential for anticipating treating disease, both stages, development hypertension. Both hypertension have assumed dimensions, complex interactions. In this Review, we present an update on discuss COVID-19. addition, summarize pathobiology COVID-19, emphasis vasculature, stage developing We hope that information presented Review will help strategies prevention treatment continuing pandemic.

Язык: Английский

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Genetic and epigenetic factors associated with increased severity of Covid‐19

Cell Biology International, Год журнала: 2021, Номер 45(6), С. 1158 - 1174

Опубликована: Фев. 16, 2021

Since December 2019, a new form of severe acute respiratory syndrome (SARS) from novel strain coronavirus (SARS 2 [SARS-CoV-2]) has been spreading worldwide. The disease caused by SARS-CoV-2 was named Covid-19 and declared as pandemic the World Health Organization in March 2020. Clinical symptoms range common cold to more defined pneumonia, hypoxia, distress. In next stage, can become critical with failure, sepsis, septic shock, and/or multiorgan failure. Outcomes indicate large gaps between male-female young-elder groups. Several theories have proposed explain variations, such gender, age, comorbidity, genetic factors. It is likely that mixture nongenetic factors interplays virus host genetics determines severity outcome. this review, we aimed summarize current literature terms potential epigenetic associated increased Covid-19. studies indicated variants entry mechanism-related (angiotensin-converting enzymes, transmembrane serine protease-2, furin) innate immune response-related genes (interferons [IFNs], interleukins, toll-like receptors), human leukocyte antigen, ABO, 3p21.31, 9q34.2 loci are determinants related severity. Epigenetic mechanisms also affect outcomes regulating IFN signaling, angiotensin-converting enzyme-2, immunity-related particularly escape X chromosome inactivation. Enhanced understanding viral interactions for improved prognostic tools innovative therapeutics.

Язык: Английский

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Thymoquinone: A Promising Natural Compound with Potential Benefits for COVID-19 Prevention and Cure

Drug Design Development and Therapy, Год журнала: 2021, Номер Volume 15, С. 1819 - 1833

Опубликована: Май 1, 2021

Abstract: COVID-19 has caused a major global health crisis, as excessive inflammation, oxidation, and exaggerated immune response in some sufferers can lead to condition known cytokine storm, which may progress acute respiratory distress syndrome (ARDs), be fatal. So far, few effective drugs have emerged assist the treatment of patients with COVID-19, though herbal medicine candidates fight against deaths. Thymoquinone (TQ), main active ingredient black seed oil, possesses antioxidant, anti-inflammatory, antiviral, antimicrobial, immunomodulatory anticoagulant activities. TQ also increases activity number suppressors, lymphocytes, natural killer cells, macrophages, it demonstrated antiviral potential viruses, including murine cytomegalovirus, Epstein-Barr virus, hepatitis C human immunodeficiency other coronaviruses. Recently, notable SARSCoV-2 strain isolated from Egyptian and, interestingly, molecular docking studies shown that could potentially inhibit development through binding receptor-binding domain on spike envelope proteins SARS-CoV-2, hinder virus entry into host cell its ion channel pore forming activity. Other an inhibitory effect SARS CoV2 proteases, diminish viral replication, good antagonism angiotensin-converting enzyme 2 receptors, allowing interfere uptake cell. Several noted protective capability numerous chronic diseases conditions, diabetes, hypertension, dyslipidemia, asthma, renal dysfunction malignancy. recently been tested clinical trials for several different diseases, this review thus aims highlight therapeutic effects context pandemic. Keywords: thymoquinone, natural, benefits

Язык: Английский

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Estrogen hormone is an essential sex factor inhibiting inflammation and immune response in COVID-19

Scientific Reports, Год журнала: 2022, Номер 12(1)

Опубликована: Июнь 8, 2022

Although vaccines have been evaluated and approved for SARS-CoV-2 infection prevention, there remains a lack of effective treatments to reduce the mortality COVID-19 patients already infected with SARS-CoV-2. The global data on showed that men higher rate than women. We further observed proportion females increases starting from around age 55 significantly. Thus, sex is an essential factor associated mortality, related genetic factors could be interesting mechanisms targets treatment. However, signaling pathways remain unclear. Here, we propose uncover potential using systematic integrative network analysis. unique results indicated estrogens, e.g., estrone estriol, (1) interacting ESR1/2 receptors, (2) can inhibit caused inflammation immune response in host cells; (3) estrogens are distinct fatality rates between male female patients. Specifically, high level estradiol protects young patients, drop extremely low after about years causing increased In conclusion, estrogen, death by inhibiting infection. Moreover, medications boosting down-stream ESR1/ESR2, or immune-associated potentially synergistic combined other existing drugs

Язык: Английский

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Epigenetic Evolution of ACE2 and IL-6 Genes: Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 Susceptibility in Vertebrates

Genes, Год журнала: 2021, Номер 12(2), С. 154 - 154

Опубликована: Янв. 25, 2021

The current novel coronavirus disease (COVID-19) has spread globally within a matter of months. virus establishes success in balancing its deadliness and contagiousness, causes substantial differences susceptibility progression people different ages, genders pre-existing comorbidities. These host factors are subjected to epigenetic regulation; therefore, relevant analyses on some key genes underlying COVID-19 pathogenesis were performed longitudinally decipher their correlation susceptibility. angiotensin-converting enzyme 2 (ACE2, as the major receptor) interleukin (IL)-6 (a immuno-pathological factor triggering cytokine storm) shown evince active evolution via histone modification cis/trans-factors interaction across vertebrate species. Extensive revealed that ACE2 ad IL-6 among subset non-canonical interferon-stimulated (non-ISGs), which have been designated for unconventional responses interferons (IFNs) inflammatory stimuli through an cascade. Furthermore, significantly higher positive markers position weight matrix (PWM) scores cis-elements corresponding IFN signaling, discovered both IL6 gene promoters representative COVID-19-susceptible species compared unsusceptible ones. findings characterize non-ISGs respond differently signaling from canonical ISGs. properties may serve biomarkers predict vertebrates partially explain inequality subgroups.

Язык: Английский

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Virus-host interaction networks as new antiviral drug targets for IAV and SARS-CoV-2

Emerging Microbes & Infections, Год журнала: 2022, Номер 11(1), С. 1371 - 1389

Опубликована: Апрель 27, 2022

Currently, SARS-CoV-2, especially the Omicron strain, is ravaging world and even co-infecting human beings with IAV, which a serious threat to public health. As of yet, no specific antiviral drug has been discovered for SARS-CoV-2. This requires deeper understandings molecular mechanisms SARS-CoV-2-host interaction, explore targets provide theoretical basis developing anti-SARS-CoV-2 drugs. article discussed comprehensively studied expected most important reference value SARS-CoV-2 study apart from members Coronaviridae family. We wish establish system studies on virus-host interaction. Previous have shown that host PRRs recognize RNAs IAV or then activate innate immune signaling pathways induce expression restriction factors, such as ISGs, ultimately inhibit viral replication. Meanwhile, viruses also evolved various regulatory antagonize immunity at transcriptional, translational, post-translational modification, epigenetic levels. Besides, can hijack supportive factors their Notably, race between antagonism forms interaction networks. Additionally, replication cycle co-regulated by proteins, ncRNAs, sugars, lipids, hormones, inorganic salts. Given this, we updated mappings based networks proposed an innovative idea new perspectives immunology systems biology.

Язык: Английский

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