Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 58
Filter
1.
Cochrane Database Syst Rev ; 10: CD013101, 2020 10 12.
Article in English | MEDLINE | ID: covidwho-1453526

ABSTRACT

BACKGROUND: Corticosteroids are routinely given to children undergoing cardiac surgery with cardiopulmonary bypass (CPB) in an attempt to ameliorate the inflammatory response. Their use is still controversial and the decision to administer the intervention can vary by centre and/or by individual doctors within that centre. OBJECTIVES: This review is designed to assess the benefits and harms of prophylactic corticosteroids in children between birth and 18 years of age undergoing cardiac surgery with CPB. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and Conference Proceedings Citation Index-Science in June 2020. We also searched four clinical trials registers and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included studies of prophylactic administration of corticosteroids, including single and multiple doses, and all types of corticosteroids administered via any route and at any time-point in the perioperative period. We excluded studies if steroids were administered therapeutically. We included individually randomised controlled trials (RCTs), with two or more groups (e.g. multi-drug or dose comparisons with a control group) but not 'head-to-head' trials without a placebo or a group that did not receive corticosteroids. We included studies in children, from birth up to 18 years of age, including preterm infants, undergoing cardiac surgery with the use of CPB. We also excluded studies in patients undergoing heart or lung transplantation, or both; studies in patients already receiving corticosteroids; in patients with abnormalities of the hypothalamic-pituitary-adrenal axis; and in patients given steroids at the time of cardiac surgery for indications other than cardiac surgery. DATA COLLECTION AND ANALYSIS: We used the Covidence systematic review manager to extract and manage data for the review. Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We resolved disagreements by consensus or by consultation with a third review author. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We found 3748 studies, of which 888 were duplicate records. Two studies had the same clinical trial registration number, but reported different populations and interventions. We therefore included them as separate studies. We screened titles and abstracts of 2868 records and reviewed full text reports for 84 studies to determine eligibility. We extracted data for 13 studies. Pooled analyses are based on eight studies. We reported the remaining five studies narratively due to zero events for both intervention and placebo in the outcomes of interest. Therefore, the final meta-analysis included eight studies with a combined population of 478 participants. There was a low or unclear risk of bias across the domains. There was moderate certainty of evidence that corticosteroids do not change the risk of in-hospital mortality (five RCTs; 313 participants; risk ratio (RR) 0.83, 95% confidence interval (CI) 0.33 to 2.07) for children undergoing cardiac surgery with CPB. There was high certainty of evidence that corticosteroids reduce the duration of mechanical ventilation (six RCTs; 421 participants; mean difference (MD) 11.37 hours lower, 95% CI -20.29 to -2.45) after the surgery. There was high-certainty evidence that the intervention probably made little to no difference to the length of postoperative intensive care unit (ICU) stay (six RCTs; 421 participants; MD 0.28 days lower, 95% CI -0.79 to 0.24) and moderate-certainty evidence that the intervention probably made little to no difference to the length of the postoperative hospital stay (one RCT; 176 participants; mean length of stay 22 days; MD -0.70 days, 95% CI -2.62 to 1.22). There was moderate certainty of evidence for no effect of the intervention on all-cause mortality at the longest follow-up (five RCTs; 313 participants; RR 0.83, 95% CI 0.33 to 2.07) or cardiovascular mortality at the longest follow-up (three RCTs; 109 participants; RR 0.40, 95% CI 0.07 to 2.46). There was low certainty of evidence that corticosteroids probably make little to no difference to children separating from CPB (one RCT; 40 participants; RR 0.20, 95% CI 0.01 to 3.92). We were unable to report information regarding adverse events of the intervention due to the heterogeneity of reporting of outcomes. We downgraded the certainty of evidence for several reasons, including imprecision due to small sample sizes, a single study providing data for an individual outcome, the inclusion of both appreciable benefit and harm in the confidence interval, and publication bias. AUTHORS' CONCLUSIONS: Corticosteroids  probably do not change the risk of mortality for children having heart surgery using CPB at any time point. They probably reduce the duration of postoperative ventilation in this context, but have little or no effect on the total length of postoperative ICU stay or total postoperative hospital stay. There was inconsistency in the adverse event outcomes reported which, consequently, could not be pooled. It is therefore impossible to provide any implications and policy-makers will be unable to make any recommendations for practice without evidence about adverse effects. The review highlighted the need for well-conducted RCTs powered for clinical outcomes to confirm or refute the effect of corticosteroids versus placebo in children having cardiac surgery with CPB. A core outcome set for adverse event reporting in the paediatric major surgery and intensive care setting is required.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Cardiac Surgical Procedures/methods , Cardiopulmonary Bypass/adverse effects , Inflammation/prevention & control , Adolescent , Adrenal Cortex Hormones/adverse effects , Bias , Cardiac Surgical Procedures/mortality , Cardiopulmonary Bypass/mortality , Cause of Death , Child , Child, Preschool , Dexamethasone/therapeutic use , Heart-Lung Machine/adverse effects , Hospital Mortality , Humans , Hydrocortisone/therapeutic use , Infant , Infant, Newborn , Inflammation/etiology , Intensive Care Units, Pediatric/statistics & numerical data , Length of Stay , Methylprednisolone/therapeutic use , Randomized Controlled Trials as Topic , Respiration, Artificial/statistics & numerical data
2.
Nat Commun ; 12(1): 4677, 2021 07 29.
Article in English | MEDLINE | ID: covidwho-1387356

ABSTRACT

SARS-CoV-2 infection can affect all human beings, including pregnant women. Thus, understanding the immunological changes induced by the virus during pregnancy is nowadays of pivotal importance. Here, using peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection, we investigate cell proliferation and cytokine production, measure plasma levels of 62 cytokines, and perform a 38-parameter mass cytometry analysis. Our results show an increase in low density neutrophils but no lymphopenia or gross alterations of white blood cells, which display normal levels of differentiation, activation or exhaustion markers and show well preserved functionality. Meanwhile, the plasma levels of anti-inflammatory cytokines such as interleukin (IL)-1RA, IL-10 and IL-19 are increased, those of IL-17, PD-L1 and D-dimer are decreased, but IL-6 and other inflammatory molecules remain unchanged. Our profiling of antiviral immune responses may thus help develop therapeutic strategies to avoid virus-induced damages during pregnancy.


Subject(s)
COVID-19/immunology , Cytokines/blood , Inflammation/immunology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/immunology , Adolescent , Adult , Asymptomatic Infections , Biomarkers/blood , COVID-19/blood , COVID-19/virology , Case-Control Studies , Cross-Sectional Studies , Cytokines/immunology , Female , Humans , Inflammation/blood , Inflammation/prevention & control , Inflammation/virology , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/blood , SARS-CoV-2/isolation & purification , Young Adult
3.
Front Immunol ; 12: 720192, 2021.
Article in English | MEDLINE | ID: covidwho-1378190

ABSTRACT

COVID-19 might lead to multi-organ failure and, in some cases, to death. The COVID-19 severity is associated with a "cytokine storm." Danger-associated molecular patterns (DAMPs) are proinflammatory molecules that can activate pattern recognition receptors, such as toll-like receptors (TLRs). DAMPs and TLRs have not received much attention in COVID-19 but can explain some of the gender-, weight- and age-dependent effects. In females and males, TLRs are differentially expressed, likely contributing to higher COVID-19 severity in males. DAMPs and cytokines associated with COVID-19 mortality are elevated in obese and elderly individuals, which might explain the higher risk for severer COVID-19 in these groups. Adenosine signaling inhibits the TLR/NF-κB pathway and, through this, decreases inflammation and DAMPs' effects. As vaccines will not be effective in all susceptible individuals and as new vaccine-resistant SARS-CoV-2 mutants might develop, it remains mandatory to find means to dampen COVID-19 disease severity, especially in high-risk groups. We propose that the regulation of DAMPs via adenosine signaling enhancement might be an effective way to lower the severity of COVID-19 and prevent multiple organ failure in the absence of severe side effects.


Subject(s)
Alarmins/immunology , COVID-19/physiopathology , Inflammation Mediators/immunology , Adenosine/metabolism , Alarmins/antagonists & inhibitors , Animals , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Humans , Inflammation/prevention & control , Inflammation Mediators/antagonists & inhibitors , Multiple Organ Failure/etiology , Multiple Organ Failure/prevention & control , Patient Acuity , Signal Transduction , Toll-Like Receptors/antagonists & inhibitors , Toll-Like Receptors/immunology
4.
Br J Nutr ; 126(10): 1564-1570, 2021 11 28.
Article in English | MEDLINE | ID: covidwho-1368881

ABSTRACT

The pandemic of Coronavirus disease 2019 (COVID-19) is rapidly progressing, causing significant morbidity and mortality. Various antiviral drugs, anti-inflammatory drugs and immunomodulators have been tried without substantial clinical benefits. The severe and critical cases of COVID-19 disease are characterised by gut microbiome dysbiosis, immune dysregulation, hyper-inflammation and hypercytokinaemia (cytokine storm). Therefore, the strategies which target these pathophysiological processes may be beneficial. Probiotics are one such strategy that exerts beneficial effects by manipulation of the gut microbiota, suppression of opportunistic pathogens in the gut, decreasing translocation of opportunistic organisms, activation of mucosal immunity and modulation of the innate and adaptive immune response. Probiotics are the potential candidates to be tested in moderate and severe cases of COVID-19 due to several beneficial effects, including easy availability, easy to administer, safe and economical to use.


Subject(s)
COVID-19/pathology , COVID-19/therapy , Probiotics , SARS-CoV-2 , COVID-19/immunology , COVID-19/mortality , Gastrointestinal Microbiome , Humans , Inflammation/pathology , Inflammation/prevention & control , Probiotics/therapeutic use
6.
Biol Aujourdhui ; 215(1-2): 63-72, 2021.
Article in French | MEDLINE | ID: covidwho-1358360

ABSTRACT

Obesity is considered a pandemic responsible for millions of deaths worldwide for many years. At the end of 2019, the Coronavirus disease 2019 (COVID-19) appeared, causing the death of more than a million people in less than a year. Numerous studies suggest that obesity could be defined as key to the onset of severe forms of this emerging disease. Indeed, SARS-CoV2 infects the host by binding to ACE2 receptors present on the surface of the cells and causes excessive secretion of pro-inflammatory cytokines including IL-1, IL-6 and TNF-α, which lead to developing acute respiratory distress syndrome (ARDS). It therefore seems essential to make up effective preventive strategies to protect this part of the population from the risk of developing a severe form of COVID-19. The ketogenic diet, which is low in sugars and high in fat, has interesting properties, both in the fight against obesity but also against severe infections. This article focuses on the latest scientific advances that make it possible to consider the ketogenic diet as a preventive strategy that simultaneously reduces the development of obesity while strengthening the immune system, two key actions in the fight against SARS-CoV2 infections and severe forms of COVID-19.


Subject(s)
COVID-19/prevention & control , Diet, Ketogenic , Inflammation/etiology , Obesity/prevention & control , Pandemics , SARS-CoV-2 , Adipocytes/metabolism , Animals , COVID-19/complications , COVID-19/immunology , COVID-19/physiopathology , Cytokine Release Syndrome/etiology , Diet, Ketogenic/adverse effects , Disease Susceptibility , Humans , Inflammation/physiopathology , Inflammation/prevention & control , Leptin/physiology , Obesity/complications , Obesity/diet therapy , Obesity/epidemiology , Respiratory Distress Syndrome/etiology
7.
Int J Mol Sci ; 22(15)2021 Jul 21.
Article in English | MEDLINE | ID: covidwho-1346495

ABSTRACT

Exosomes are nano-sized vesicles secreted by most cells that contain a variety of biological molecules, such as lipids, proteins and nucleic acids. They have been recognized as important mediators for long-distance cell-to-cell communication and are involved in a variety of biological processes. Exosomes have unique advantages, positioning them as highly effective drug delivery tools and providing a distinct means of delivering various therapeutic agents to target cells. In addition, as a new clinical diagnostic biomarker, exosomes play an important role in many aspects of human health and disease, including endocrinology, inflammation, cancer, and cardiovascular disease. In this review, we summarize the development of exosome-based drug delivery tools and the validation of novel biomarkers, and illustrate the role of exosomes as therapeutic targets in the prevention and treatment of various diseases.


Subject(s)
Biomarkers/metabolism , Cardiovascular Diseases/prevention & control , Drug Delivery Systems , Exosomes/metabolism , Inflammation/prevention & control , Neoplasms/prevention & control , Pharmaceutical Preparations/administration & dosage , Cardiovascular Diseases/metabolism , Humans , Inflammation/metabolism , Neoplasms/metabolism
8.
Sci Adv ; 7(32)2021 08.
Article in English | MEDLINE | ID: covidwho-1343935

ABSTRACT

We investigated the influence of Bacillus Calmette-Guérin (BCG) vaccination on the unstimulated plasma levels of a wide panel of cytokines, chemokines, acute-phase proteins (APPs), matrix metalloproteinases (MMPs), and growth factors in a group of healthy elderly individuals (age, 60 to 80 years) at baseline (before vaccination) and 1 month after vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Our results demonstrated that BCG vaccination resulted in diminished plasma levels of types 1, 2, and 17 and other proinflammatory cytokines and type 1 interferons. BCG vaccination also resulted in decreased plasma levels of CC, CXC chemokines, APPs, MMPs, and growth factors. Plasma levels of the aforementioned parameters were significantly lower in vaccinated individuals when compared to unvaccinated control individuals. Thus, our study demonstrates the immunomodulatory properties of BCG vaccination and suggests its potential utility in nonspecific vaccination of COVID-19 by down-modulating pathogenic inflammatory responses.


Subject(s)
BCG Vaccine/administration & dosage , COVID-19/immunology , Cytokines/metabolism , Inflammation Mediators/metabolism , Inflammation/prevention & control , Vaccination/methods , Aged , Aged, 80 and over , BCG Vaccine/immunology , COVID-19/epidemiology , COVID-19/virology , Case-Control Studies , Female , Humans , India/epidemiology , Inflammation/immunology , Inflammation/metabolism , Inflammation/pathology , Male , Middle Aged , SARS-CoV-2/immunology
9.
Nutrients ; 13(7)2021 Jul 15.
Article in English | MEDLINE | ID: covidwho-1314706

ABSTRACT

Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose-response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.


Subject(s)
Fatty Acids, Omega-3/therapeutic use , Fatty Acids, Omega-6/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , Cardiovascular Diseases/prevention & control , Humans , Inflammation/prevention & control , Oxidative Stress/drug effects
10.
Ther Drug Monit ; 43(4): 455-458, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1305444

ABSTRACT

ABSTRACT: In this article, we present a case of apixaban elimination prolonged by 450% in a patient with coronavirus disease 2019 because of multiple conditions, including drug-drug interaction, severe inflammation, and acute kidney injury. Therapeutic drug monitoring was used to explain unusual routine coagulation assays. This grand round highlights the importance of dialog between the clinician and a therapeutic drug monitoring consultant for optimal patient care.


Subject(s)
Acute Kidney Injury/metabolism , COVID-19/metabolism , Drug Monitoring/methods , Pyrazoles/metabolism , Pyridones/metabolism , Renal Elimination/drug effects , Teaching Rounds/methods , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Aged, 80 and over , Antiviral Agents/adverse effects , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Interactions/physiology , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/metabolism , Factor Xa Inhibitors/therapeutic use , Humans , Inflammation/chemically induced , Inflammation/metabolism , Inflammation/prevention & control , Male , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Pyridones/adverse effects , Pyridones/therapeutic use , Renal Elimination/physiology , Severity of Illness Index , Time Factors
11.
PLoS One ; 16(7): e0254167, 2021.
Article in English | MEDLINE | ID: covidwho-1295525

ABSTRACT

Dexamethasone provides benefits in patients with coronavirus disease 2019 (COVID-19), although data regarding immunological profiles and viral clearance are limited. This study aimed to evaluate for differences in biomarkers among patients with severe COVID-19 who did and did not receive dexamethasone. We measured plasma biomarkers of lung epithelial/endothelial injury and inflammation in 31 patients with severe COVID-19 and in 13 controls. Changes in biomarkers and clinical parameters were compared during the 7-day period among COVID-19 patients, and also according to dexamethasone use. Thirty-two patients with severe COVID-19 who received mechanical ventilation (n = 6), high-flow nasal cannula (n = 11), and supplemental oxygen (n = 15) were analyzed. Relative to controls, patients with severe COVID-19 had significantly higher concentrations of biomarkers related to glycocalyx shedding (endocan and syndecan-1), endothelial injury (von Willebrand factor), and inflammation (soluble receptor for advanced glycation end-products [sRAGE] and interleukin-6). The 7-day decreases in biomarkers of endothelial injury (angiopoietin-2 [Ang-2] and intercellular adhesion molecule-1 [ICAM-1]) and sRAGE, but not in the biomarker of lung epithelial injury (surfactant protein D), were correlated with decreases in C-reactive protein and radiologic score at day 7. Twenty patients (63%) received dexamethasone, and the dexamethasone and non-dexamethasone groups differed in terms of disease severity. However, dexamethasone was associated marginally with increased SpO2/FiO2 and significantly with decreases in C-reactive protein and radiologic score after adjusting for baseline imbalances. Furthermore, the dexamethasone group exhibited a significant decrease in the concentrations of Ang-2, ICAM-1, soluble form of the Tie2 receptor (a biomarker of glycocalyx shedding), and sRAGE. Both groups exhibited a clinically insignificant increase in the cycle threshold value. Severe COVID-19 may be characterized by more severe endothelial injury and inflammation, and less severe lung epithelial injury. There is a possibility that dexamethasone improved severe COVID-19 and related endothelial injury without delaying viral clearance.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Endothelium, Vascular/drug effects , Inflammation/prevention & control , SARS-CoV-2 , Viremia/drug therapy , Adult , Aged , Anti-Inflammatory Agents/pharmacology , Biomarkers , COVID-19/blood , COVID-19/diagnostic imaging , Dexamethasone/pharmacology , Endothelium, Vascular/pathology , Female , Humans , Inflammation/blood , Inflammation/etiology , Lung Injury/blood , Lung Injury/diagnostic imaging , Lung Injury/etiology , Male , Oxygen/blood , Pilot Projects , Viral Load , Viremia/blood
12.
J Nanobiotechnology ; 19(1): 173, 2021 Jun 10.
Article in English | MEDLINE | ID: covidwho-1266489

ABSTRACT

BACKGROUND: The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. RESULTS: Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. CONCLUSION: Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , Biomimetics , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , Drug Carriers , Inflammation/prevention & control , Nanoparticles , SARS-CoV-2/drug effects , COVID-19/virology , Cytokine Release Syndrome/etiology , Humans , Inflammation/complications , SARS-CoV-2/isolation & purification
13.
Crit Care ; 25(1): 178, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243817

ABSTRACT

A growing consensus seems to be emerging that dexamethasone is a crucial component in the treatment of COVID-19-associated oxygen-dependent respiratory failure. Although dexamethasone has an undeniably beneficial effect on the inflammatory response in a subgroup of patients, the potential negative effects of corticosteroids must also be considered. In view of these negative effects, we argue that a one-size-fits-all dexamethasone approach may be potentially harmful in specific subsets of patients with COVID-19-associated ARDS. We propose a different individually tailored treatment strategy based on the patient's inflammatory response.


Subject(s)
COVID-19/drug therapy , Critical Care/methods , Dexamethasone/therapeutic use , Inflammation/prevention & control , Respiratory Insufficiency/drug therapy , COVID-19/complications , Dexamethasone/adverse effects , Humans , Intensive Care Units , Respiratory Insufficiency/virology , Treatment Outcome
14.
Ther Drug Monit ; 43(4): 455-458, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1205884

ABSTRACT

ABSTRACT: In this article, we present a case of apixaban elimination prolonged by 450% in a patient with coronavirus disease 2019 because of multiple conditions, including drug-drug interaction, severe inflammation, and acute kidney injury. Therapeutic drug monitoring was used to explain unusual routine coagulation assays. This grand round highlights the importance of dialog between the clinician and a therapeutic drug monitoring consultant for optimal patient care.


Subject(s)
Acute Kidney Injury/metabolism , COVID-19/metabolism , Drug Monitoring/methods , Pyrazoles/metabolism , Pyridones/metabolism , Renal Elimination/drug effects , Teaching Rounds/methods , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Aged, 80 and over , Antiviral Agents/adverse effects , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Interactions/physiology , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/metabolism , Factor Xa Inhibitors/therapeutic use , Humans , Inflammation/chemically induced , Inflammation/metabolism , Inflammation/prevention & control , Male , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Pyridones/adverse effects , Pyridones/therapeutic use , Renal Elimination/physiology , Severity of Illness Index , Time Factors
15.
J Biol Chem ; 296: 100687, 2021.
Article in English | MEDLINE | ID: covidwho-1198855

ABSTRACT

Glucocorticoids are potent anti-inflammatory drugs that are used to treat an extraordinary range of human disease, including COVID-19, underscoring the ongoing importance of understanding their molecular mechanisms. Early studies of GR signaling led to broad acceptance of models in which glucocorticoid receptor (GR) monomers tether repressively to inflammatory transcription factors, thus abrogating inflammatory gene expression. However, newer data challenge this core concept and present an exciting opportunity to reframe our understanding of GR signaling. Here, we present an alternate, two-part model for transcriptional repression by glucocorticoids. First, widespread GR-mediated induction of transcription results in rapid, primary repression of inflammatory gene transcription and associated enhancers through competition-based mechanisms. Second, a subset of GR-induced genes, including targets that are regulated in coordination with inflammatory transcription factors such as NF-κB, exerts secondary repressive effects on inflammatory gene expression. Within this framework, emerging data indicate that the gene set regulated through the cooperative convergence of GR and NF-κB signaling is central to the broad clinical effectiveness of glucocorticoids in terminating inflammation and promoting tissue repair.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , NF-kappa B/genetics , Receptors, Glucocorticoid/genetics , Animals , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Gene Expression Regulation , Genomics/methods , Humans , Inflammation/prevention & control , Models, Genetic , NF-kappa B/antagonists & inhibitors , NF-kappa B/immunology , Receptors, Glucocorticoid/agonists , Receptors, Glucocorticoid/immunology , SARS-CoV-2/growth & development , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Signal Transduction , Transcription, Genetic/drug effects , Transcription, Genetic/immunology
16.
BMC Complement Med Ther ; 21(1): 112, 2021 Apr 07.
Article in English | MEDLINE | ID: covidwho-1172831

ABSTRACT

BACKGROUND: Elderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of 'cytokine storm'. We aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines. METHODS: We conducted a systematic review and searched six databases, four research registers, and two preprint sites for studies. Two reviewers independently assessed studies for inclusion, extracted data from studies, assessed risk of bias using Cochrane tools, and evaluated certainty of estimates using GRADE. Outcomes included new illnesses and the severity and duration of illness. RESULTS: We screened 1187 records and included five randomized trials on elderberry for the treatment or prevention of viral respiratory illness. We did not find any studies linking elderberry to clinical inflammatory outcomes. However, we found three studies measuring production of cytokines ex vivo after ingestion of elderberry. Elderberry may not reduce the risk of developing the common cold; it may reduce the duration and severity of colds, but the evidence is uncertain. Elderberry may reduce the duration of influenza but the evidence is uncertain. Compared to oseltamivir, an elderberry-containing product may be associated with a lower risk of influenza complications and adverse events. We did not find evidence on elderberry and clinical outcomes related to inflammation. However, we found evidence that elderberry has some effect on inflammatory markers, although this effect may decline with ongoing supplementation. One small study compared elderberry to diclofenac (a nonsteroidal anti-inflammatory drug) and provided some evidence that elderberry is as effective or less effective than diclofenac in cytokine reduction over time. CONCLUSIONS: Elderberry may be a safe option for treating viral respiratory illness, and there is no evidence that it overstimulates the immune system. However, the evidence on both benefits and harms is uncertain and information from recent and ongoing studies is necessary to make firm conclusions.


Subject(s)
COVID-19/drug therapy , Common Cold/drug therapy , Cytokines/metabolism , Influenza, Human/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Sambucus , COVID-19/metabolism , Common Cold/metabolism , Humans , Inflammation/metabolism , Inflammation/prevention & control , Influenza, Human/metabolism , Pandemics , SARS-CoV-2
17.
Nutrients ; 13(3)2021 Mar 20.
Article in English | MEDLINE | ID: covidwho-1143547

ABSTRACT

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.


Subject(s)
COVID-19/diet therapy , Diet, Ketogenic/methods , COVID-19/etiology , COVID-19/prevention & control , Humans , Inflammation/prevention & control , Obesity/complications , Respiratory System/physiopathology , Respiratory System/virology
18.
Food Chem Toxicol ; 149: 112007, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1139498

ABSTRACT

Consistent gathering of immunotoxic substances on earth is a serious global issue affecting people under pathogenic stress. Organophosphates are among such hazardous compounds that are ubiquitous in nature. They fuel oxidative stress to impair antiviral immune response in living entities. Aside, organophosphates promote cytokine burst and pyroptosis in broncho-alveolar chambers leading to severe respiratory ailments. At present, we witness COVID-19 outbreak caused by SARS-CoV-2. Infection triggers cytokine storm coupled with inflammatory manifestations and pulmonary disorders in patients. Since organophosphate-exposure promotes necroinflammation and respiratory troubles hence during current pandemic situation, additional exposure to such chemicals can exacerbate inflammatory outcome and pulmonary maladies in patients, or pre-exposure to organophosphates might turn-out to be a risk factor for compromised immunity. Fortunately, antioxidants alleviate organophosphate-induced immunosuppression and hence under co-exposure circumstances, dietary intake of antioxidants would be beneficial to boost immunity against SARS-CoV-2 infection.


Subject(s)
COVID-19 , Environmental Exposure/adverse effects , Immunity/drug effects , Inflammation/etiology , Organophosphates/adverse effects , Oxidative Stress/drug effects , SARS-CoV-2/pathogenicity , Animals , Antioxidants/therapeutic use , COVID-19/immunology , COVID-19/virology , Cytokine Release Syndrome , Cytokines/metabolism , Humans , Inflammation/metabolism , Inflammation/prevention & control , Pandemics , Pesticides/adverse effects , Pyroptosis , Respiratory Tract Diseases/etiology , Virulence/drug effects
19.
Curr Atheroscler Rep ; 22(9): 48, 2020 07 25.
Article in English | MEDLINE | ID: covidwho-1103544

ABSTRACT

PURPOSE OF REVIEW: The COVID-19 pandemic has infected over > 11 million as of today people worldwide and is associated with significant cardiovascular manifestations, particularly in subjects with preexisting comorbidities and cardiovascular risk factors. Recently, a predisposition for arterial and venous thromboses has been reported in COVID-19 infection. We hypothesize that besides conventional risk factors, subjects with elevated lipoprotein(a) (Lp(a)) may have a particularly high risk of developing cardiovascular complications. RECENT FINDINGS: The Lp(a) molecule has the propensity for inhibiting endogenous fibrinolysis through its apolipoprotein(a) component and for enhancing proinflammatory effects such as through its content of oxidized phospholipids. The LPA gene contains an interleukin-6 (IL-6) response element that may induce an acute phase-type increase in Lp(a) levels following a cytokine storm from COVID-19. Thus, subjects with either baseline elevated Lp(a) or those who have an increase following COVID-19 infection, or both, may be at very high risk of developing thromboses. Elevated Lp(a) may also lead to acute destabilization of preexisting but quiescent atherosclerotic plaques, which might induce acute myocardial infarction and stroke. Ongoing studies with IL-6 antagonists may be informative in understanding this relationship, and registries are being initiated to measure Lp(a) in subjects infected with COVID-19. If indeed an association is suggestive of being causal, consideration can be given to systematic testing of Lp(a) and prophylactic systemic anticoagulation in infected inpatients. Therapeutic lipid apheresis and pharmacotherapy for the reduction of Lp(a) levels may minimize thrombogenic potential and proinflammatory effects. We propose studies to test the hypothesis that Lp(a) may contribute to cardiovascular complications of COVID-19.


Subject(s)
Coronavirus Infections/blood , Coronavirus Infections/complications , Inflammation/etiology , Lipoprotein(a)/blood , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Thrombosis/etiology , Acute-Phase Proteins/analysis , Acute-Phase Proteins/genetics , Anticoagulants/therapeutic use , Apolipoprotein E4/genetics , Atherosclerosis/etiology , Betacoronavirus , Biomarkers/blood , Biomedical Research , Blood Component Removal , COVID-19 , Coronavirus Infections/epidemiology , Genotype , Humans , Inflammation/prevention & control , Interleukin-6/antagonists & inhibitors , Interleukin-6/blood , Lipoprotein(a)/genetics , Pandemics , Pneumonia, Viral/epidemiology , Race Factors , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Thrombosis/prevention & control
20.
Nutrients ; 13(2)2021 Feb 05.
Article in English | MEDLINE | ID: covidwho-1094259

ABSTRACT

Cardiovascular disease (CVD) is the leading cause of death worldwide, claiming over 650,000 American lives annually. Typically not a singular disease, CVD often coexists with dyslipidemia, hypertension, type-2 diabetes (T2D), chronic system-wide inflammation, and obesity. Obesity, an independent risk factor for both CVD and T2D, further worsens the problem, with over 42% of adults and 18.5% of youth in the U.S. categorized as such. Dietary behavior is a most important modifiable risk factor for controlling the onset and progression of obesity and related disease conditions. Plant-based eating patterns that include beans and legumes support health and disease mitigation through nutritional profile and bioactive compounds including phytochemical. This review focuses on the characteristics of beans and ability to improve obesity-related diseases and associated factors including excess body weight, gut microbiome environment, and low-grade inflammation. Additionally, there are growing data that link obesity to compromised immune response and elevated risk for complications from immune-related diseases. Body weight management and nutritional status may improve immune function and possibly prevent disease severity. Inclusion of beans as part of a plant-based dietary strategy imparts cardiovascular, metabolic, and colon protective effects; improves obesity, low-grade inflammation, and may play a role in immune-related disease risk management.


Subject(s)
Cardiovascular Diseases/prevention & control , Diet, Vegetarian/methods , Fabaceae , Obesity/prevention & control , Amino Acids/administration & dosage , COVID-19/complications , Cardiovascular Diseases/epidemiology , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/prevention & control , Dietary Proteins/administration & dosage , Dysbiosis/etiology , Dyslipidemias/epidemiology , Dyslipidemias/prevention & control , Endothelium, Vascular/physiopathology , Fabaceae/chemistry , Fatty Acid Synthases , Female , Gastrointestinal Microbiome/physiology , Glycemic Control , Humans , Hypertension/epidemiology , Hypertension/prevention & control , Immune System Diseases/prevention & control , Inflammation/epidemiology , Inflammation/prevention & control , Male , Minerals/administration & dosage , NADH, NADPH Oxidoreductases , Nutritional Status , Obesity/epidemiology , Obesity/immunology , Overweight/complications , Phaseolus/chemistry , Recommended Dietary Allowances , Risk Factors , Vitamins/administration & dosage
SELECTION OF CITATIONS
SEARCH DETAIL
...