scholarly journals Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients

2020 ◽  
Author(s):  
Amr H. Sawalha ◽  
Ming Zhao ◽  
Patrick Coit ◽  
Qianjin Lu
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Viral Entry ◽  
Viral Infections ◽  
Severe Disease ◽  
Disease Course ◽  
Vicious Cycle ◽  
Respiratory Complications ◽  
Disease Remission ◽  
Functional Receptor

SummaryInfection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specially, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections

2021 ◽  
Author(s):  
Karthick Dharmalingam ◽  
Amandeep Birdi ◽  
Sojit Tomo ◽  
Karli Sreenivasulu ◽  
Jaykaran Charan ◽  
...  
Keyword(s):  
Immune Response ◽  
Trace Elements ◽  
Viral Entry ◽  
Viral Infections ◽  
Inhibitory Effect ◽  
Antioxidants Activity ◽  
Host Immune Responses ◽  
Complex Interactions ◽  
Downstream Processes

AbstractNutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words “Trace elements”, “COVID-19”, “Viral Infections” and “Immune Response” (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

scholarly journals THE BIOLOGICAL SIGNIFICANCE OF SELENIUM AND ITS PLACE IN RNA VIRAL DISEASES

2020 ◽  
Vol 21 (4) ◽  
pp. 21-31
Author(s):  
T.M. Guseynov ◽  
◽  
R.T. Guliyeva ◽  
F.R. Yakhyayeva ◽  
◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Viral Infections ◽  
Biological Significance ◽  
The Body ◽  
Viral Diseases ◽  
Essential Trace Element ◽  
Regulatory Processes ◽  
P Protein ◽  
Almost All

ABSTRACT. Selenium as an essential trace element takes part in the regulation of many vital processes. This is realized with the help of over 25 selenoproteins that affect oxidative stress, immune response, hormonal metabolism, cognitive function, etc. Recently (in the next 30 - 40 years), there have been reports of the effect on viral infections, which have now become widespread. It turned out that almost all RNA viruses are selenium-dependent objects, that is, their genome contains the codes of the most important selenium containing proteins, including such as glutathione peroxidase, thioredoxinreductase, selenium-P protein, etc. Their synthesis during the development of a viral infection at the expense of the host leads to a weakening of the synthesis of the body's own intracellular selenium proteins, which contributes to the development of oxidative stress and a failure of the immune response. And this leads to the devastation of the selenium depot of the body, intended for the synthesis of its selenium proteins, which participate in vital regulatory processes. This circumstance determines, to replenish the body's resources with selenium, the expediency of using selenium-containing pharmacopoeia preparations as adjuvant in the treatment of RNA viral infections.

scholarly journals Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Vincent J. Venditto ◽  
Dalia Haydar ◽  
Ahmed Abdel-Latif ◽  
John C. Gensel ◽  
Michael I. Anstead ◽  
...  
Keyword(s):  
Immune Response ◽  
Severe Disease ◽  
Lung Pathology ◽  
Disease Course ◽  
Immunomodulatory Effects ◽  
Therapeutic Success ◽  
Published Evidence ◽  
Potential Applications ◽  
Regulatory Functions ◽  
Immunomodulatory Therapies

The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support the premise of targeting the immune response. However, because suppressing immune mechanisms could also impact the clearance of the virus in the early stages of infection, therapeutic success is likely to depend on timing with respect to the disease course. Azithromycin is an immunomodulatory drug that has been shown to have antiviral effects and potential benefit in patients with COVID-19. Multiple immunomodulatory effects have been defined for azithromycin which could provide efficacy during the late stages of the disease, including inhibition of pro-inflammatory cytokine production, inhibition of neutrophil influx, induction of regulatory functions of macrophages, and alterations in autophagy. Here we review the published evidence of these mechanisms along with the current clinical use of azithromycin as an immunomodulatory therapeutic. We then discuss the potential impact of azithromycin on the immune response to COVID-19, as well as caution against immunosuppressive and off-target effects including cardiotoxicity in these patients. While azithromycin has the potential to contribute efficacy, its impact on the COVID-19 immune response requires additional characterization so as to better define its role in individualized therapy.

scholarly journals Flavonoids Activation of the Transcription Factor Nrf2 as a Hypothesis Approach for the Prevention and Modulation of SARS-CoV-2 Infection Severity

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 659 ◽  
Author(s):  
Patricia Mendonca ◽  
Karam F. A. Soliman
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Viral Entry ◽  
Viral Infections ◽  
Ros Generation ◽  
Respiratory Epithelial Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Impaired Immune Response ◽  
Respiratory Epithelial ◽  
And Oxidative Stress

The Nrf2-Keap1-ARE pathway is the principal regulator of antioxidant and phase II detoxification genes. Its activation increases the expression of antioxidant and cytoprotective proteins, protecting cells against infections. Nrf2 modulates virus-induced oxidative stress, ROS generation, and disease pathogenesis, which are vital in the viral life cycle. During respiratory viral infections, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an inflammatory process, and oxidative stress of the epithelium lining cells activate the transcription factor Nrf2, which protects cells from oxidative stress and inflammation. Nrf2 reduces angiotensin-converting enzyme 2 (ACE2) receptors expression in respiratory epithelial cells. SARS-CoV2 has a high affinity for ACE2 that works as receptors for coronavirus surface spike glycoprotein, facilitating viral entry. Disease severity may also be modulated by pre-existing conditions, such as impaired immune response, obesity, and age, where decreased level of Nrf2 is a common feature. Consequently, Nrf2 activators may increase Nrf2 levels and enhance antiviral mediators’ expression, which could initiate an “antiviral state”, priming cells against viral infection. Therefore, this hypothesis paper describes the use of flavonoid supplements combined with vitamin D3 to activate Nrf2, which may be a potential target to prevent and/or decrease SARS-CoV-2 infection severity, reducing oxidative stress and inflammation, enhancing innate immunity, and downregulating ACE2 receptors.

scholarly journals Steroid harms if given early in COVID-19 viraemia

2021 ◽  
Vol 14 (2) ◽  
pp. e241105
Author(s):  
Kanupriya Arora ◽  
Prasan Kumar Panda
Keyword(s):  
Immune Response ◽  
Immune Regulation ◽  
Severe Disease ◽  
Preventive Measure ◽  
Disease Course ◽  
Supportive Treatment ◽  
Cytokine Storm ◽  
Adaptive Immune ◽  
The One ◽  
Anti Inflammation

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.

scholarly journals Cell type-specific immune dysregulation in severely ill COVID-19 patients

2020 ◽  
Author(s):  
Changfu Yao ◽  
Stephanie A Bora ◽  
Tanyalak Parimon ◽  
Tanzira Zaman ◽  
Oren A Friedman ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Ventilatory Support ◽  
Adaptive Immune Response ◽  
Disease Course ◽  
B Cell Activation ◽  
Peripheral Blood Mononuclear ◽  
Mild Disease

Coronavirus disease 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury called acute respiratory distress syndrome (ARDS) that causes progressive respiratory failure requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease course in COVID-19.

scholarly journals Oxysterols in the Immune Response to Bacterial and Viral Infections

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 201
Author(s):  
Cheng Xiang Foo ◽  
Stacey Bartlett ◽  
Katharina Ronacher
Keyword(s):  
Immune Response ◽  
Host Cell ◽  
Bacterial Growth ◽  
Viral Entry ◽  
Drug Targets ◽  
Viral Infections ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Lipid Mediators ◽  
Cholesterol Homeostasis

Oxidized cholesterols, the so-called oxysterols, are widely known to regulate cholesterol homeostasis. However, more recently oxysterols have emerged as important lipid mediators in the response to both bacterial and viral infections. This review summarizes our current knowledge of selected oxysterols and their receptors in the control of intracellular bacterial growth as well as viral entry into the host cell and viral replication. Lastly, we briefly discuss the potential of oxysterols and their receptors as drug targets for infectious and inflammatory diseases.

scholarly journals The epidemiology, clinical presentation, and predictors of severe Tick-borne encephalitis in Lithuania, a highly endemic country: A retrospective study of 1040 patients

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241587
Author(s):  
Daiva Radzišauskienė ◽  
Jurgita Urbonienė ◽  
Gintaras Kaubrys ◽  
Saulius Andruškevičius ◽  
Dalius Jatužis ◽  
...  
Keyword(s):  
Immune Response ◽  
Retrospective Study ◽  
Clinical Presentation ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
University Hospital ◽  
Disease Course ◽  
Tick Borne Encephalitis ◽  
Vilnius University ◽  
Severity Of The Disease

Introduction In recent decades, the incidence of Tick-borne encephalitis (TBE) has been increasing and posing a growing health problem because of the high costs to the healthcare system and society. The clinical manifestations are well studied but there is a lack of research analyzing the severity of the disease. Objective The aim of this study was to analyze the epidemiology and clinical presentation of severe TBE, to identify the predictors for a severe disease course, and also predictors for meningoencephalomyelitic and severe meningoencephalitic/encephalitic forms. Methods A retrospective study was conducted in the Center of Infectious Diseases and the Center of Neurology at Vilnius University Hospital Santaros Klinikos in the years 2005–2017 to describe the clinical and epidemiological features of TBE in adults. Results 1040 patients were included in the study. A total of 152/1040 (14.6%) patients had a severe course. The highest proportion of severe cases, reaching 41.2%, was reported in the 70–79 year-old age group. A total of 36/152 (23.7%) severe patients presented meningoencephalomyelitis. Myelitic patients were older, were frequently infected in their living areas, and usually reported a monophasic disease course compared with severe meningoencephalitic/encephalitic patients. Severe meningoencephalitic/encephalitic patients, compared with non-severe meningoencephalitic/encephalitic, were older, less often noticed the tick bite, and often had a monophasic course. The sequelae on discharge were observed in 810/1000 (81%) of patients. Conclusions The prognostic factors associated with a severe disease course and severe meningoencephalitic form are: older age, comorbidities, a monophasic course, a fever of 40˚C and above, CRP more than 30 mg/l, CSF protein more than 1 g/l, delayed immune response of TBEV IgG, pathological findings in CT. Age above 60 years, presence of CNS disease, bulbar syndrome, pleocytosis 500x106/l and above, and delayed immune response of TBEV IgG are predictors of the most severe myelitic form.

scholarly journals Crossing the Iron Gate: Why and How Transferrin Receptors Mediate Viral Entry

2018 ◽  
Vol 38 (1) ◽  
pp. 431-458 ◽  
Author(s):  
Marianne Wessling-Resnick
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Iron Metabolism ◽  
Viral Entry ◽  
Transferrin Receptor ◽  
Host Immunity ◽  
Innate Immune ◽  
Transferrin Receptors ◽  
Iron Gate ◽  
Viral Target

Because both the host and pathogen require iron, the innate immune response carefully orchestrates control over iron metabolism to limit its availability during times of infection. Nutritional iron deficiency can impair host immunity, while iron overload can cause oxidative stress to propagate harmful viral mutations. An emerging enigma is that many viruses use the primary gatekeeper of iron metabolism, the transferrin receptor, as a means to enter cells. Why and how this iron gate is a viral target for infection are the focus of this review.

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