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1.
Lancet Infect Dis ; 20(11): e276-e288, 2020 11.
Article in English | MEDLINE | ID: covidwho-2062013

ABSTRACT

As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions. However, the association between multisystem inflammatory syndrome in children and COVID-19 is still unknown. We review the epidemiology, causes, clinical features, and current treatment protocols for multisystem inflammatory syndrome in children and adolescents associated with COVID-19. We also discuss the possible underlying pathophysiological mechanisms for COVID-19-induced inflammatory processes, which can lead to organ damage in paediatric patients who are severely ill. These insights provide evidence for the need to develop a clear case definition and treatment protocol for this new condition and also shed light on future therapeutic interventions and the potential for vaccine development. TRANSLATIONS: For the French, Chinese, Arabic, Spanish and Russian translations of the abstract see Supplementary Materials section.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/immunology , Adolescent , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Child , Child, Preschool , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Infant , Infant, Newborn , Male , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/immunology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Risk Factors , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/virology , Young Adult
2.
Int J Mol Sci ; 21(14)2020 Jul 08.
Article in English | MEDLINE | ID: covidwho-1934087

ABSTRACT

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are characterized by an inflammatory response, alveolar edema, and hypoxemia. ARDS occurs most often in the settings of pneumonia, sepsis, aspiration of gastric contents, or severe trauma. The prevalence of ARDS is approximately 10% in patients of intensive care. There is no effective remedy with mortality high at 30-40%. Most functional proteins are dynamic and stringently governed by ubiquitin proteasomal degradation. Protein ubiquitination is reversible, the covalently attached monoubiquitin or polyubiquitin moieties within the targeted protein can be removed by a group of enzymes called deubiquitinating enzymes (DUBs). Deubiquitination plays an important role in the pathobiology of ALI/ARDS as it regulates proteins critical in engagement of the alveolo-capillary barrier and in the inflammatory response. In this review, we provide an overview of how DUBs emerge in pathogen-induced pulmonary inflammation and related aspects in ALI/ARDS. Better understanding of deubiquitination-relatedsignaling may lead to novel therapeutic approaches by targeting specific elements of the deubiquitination pathways.


Subject(s)
Acute Lung Injury/metabolism , Deubiquitinating Enzymes/metabolism , Respiratory Distress Syndrome/metabolism , Animals , Humans , Pneumonia/metabolism , Signal Transduction/physiology , Ubiquitin/metabolism , Ubiquitination/physiology
3.
J Immunotoxicol ; 18(1): 23-29, 2021 12.
Article in English | MEDLINE | ID: covidwho-1593522

ABSTRACT

The coronavirus SARS-CoV-2 of 2019 (COVID-19) causes a pandemic that has been diagnosed in more than 70 million people worldwide. Mild-to-moderate COVID-19 symptoms include coughing, fever, myalgia, shortness of breath, and acute inflammatory lung injury (ALI). In contrast, acute respiratory distress syndrome (ARDS) and respiratory failure occur in patients diagnosed with severe COVID-19. ARDS is mediated, at least in part, by a dysregulated inflammatory response due to excessive levels of circulating cytokines, a condition known as the "cytokine-storm syndrome." Currently, there are FDA-approved therapies that attenuate the dysregulated inflammation that occurs in COVID-19 patients, such as dexamethasone or other corticosteroids and IL-6 inhibitors, including sarilumab, tocilizumab, and siltuximab. However, the efficacy of these treatments have been shown to be inconsistent. Compounds that activate the vagus nerve-mediated cholinergic anti-inflammatory reflex, such as the α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuate ARDS/inflammatory lung injury by decreasing the extracellular levels of high mobility group box-1 (HMGB1) in the airways and the circulation. It is possible that HMGB1 may be an important mediator of the "cytokine-storm syndrome." Notably, high plasma levels of HMGB1 have been reported in patients diagnosed with severe COVID-19, and there is a significant negative correlation between HMGB1 plasma levels and clinical outcomes. Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines. Therefore, we hypothesize that low molecular weight compounds that activate the cholinergic anti-inflammatory reflex, such as nicotine or GTS-21, may represent a potential therapeutic approach to attenuate the dysregulated inflammatory responses in patients with severe COVID-19.


Subject(s)
Benzylidene Compounds/pharmacology , COVID-19/drug therapy , Cholinergic Agents/pharmacology , Inflammation/drug therapy , Nicotine/metabolism , Pyridines/pharmacology , SARS-CoV-2/physiology , Tobacco Use Disorder/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Cigarette Smoking/adverse effects , Dexamethasone/therapeutic use , HMGB1 Protein/blood , Humans , Pandemics , alpha7 Nicotinic Acetylcholine Receptor/agonists
4.
J Neuroinflammation ; 18(1): 123, 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1571835

ABSTRACT

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is a member of the NLR family of inherent immune cell sensors. The NLRP3 inflammasome can detect tissue damage and pathogen invasion through innate immune cell sensor components commonly known as pattern recognition receptors (PRRs). PRRs promote activation of nuclear factor kappa B (NF-κB) pathways and the mitogen-activated protein kinase (MAPK) pathway, thus increasing the transcription of genes encoding proteins related to the NLRP3 inflammasome. The NLRP3 inflammasome is a complex with multiple components, including an NAIP, CIITA, HET-E, and TP1 (NACHT) domain; apoptosis-associated speck-like protein containing a CARD (ASC); and a leucine-rich repeat (LRR) domain. After ischemic stroke, the NLRP3 inflammasome can produce numerous proinflammatory cytokines, mediating nerve cell dysfunction and brain edema and ultimately leading to nerve cell death once activated. Ischemic stroke is a disease with high rates of mortality and disability worldwide and is being observed in increasingly younger populations. To date, there are no clearly effective therapeutic strategies for the clinical treatment of ischemic stroke. Understanding the NLRP3 inflammasome may provide novel ideas and approaches because targeting of upstream and downstream molecules in the NLRP3 pathway shows promise for ischemic stroke therapy. In this manuscript, we summarize the existing evidence regarding the composition and activation of the NLRP3 inflammasome, the molecules involved in inflammatory pathways, and corresponding drugs or molecules that exert effects after cerebral ischemia. This evidence may provide possible targets or new strategies for ischemic stroke therapy.


Subject(s)
Inflammasomes/drug effects , Inflammasomes/metabolism , Inflammation/metabolism , Inflammation/therapy , Ischemic Stroke/metabolism , Ischemic Stroke/therapy , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Animals , Brain/metabolism , Brain/pathology , COVID-19/complications , Humans
5.
Jpn J Infect Dis ; 74(6): 530-536, 2021 Nov 22.
Article in English | MEDLINE | ID: covidwho-1534555

ABSTRACT

It is important to determine the inflammatory biomarkers in the severity of coronavirus disease 2019 (COVID-19) with the emergence of the pandemic. Galectins and prostaglandins play important roles in the regulation of immune and inflammatory responses. Therefore, this study aimed to investigate Galectin-1 (Gal-1), Galectin-3 (Gal-3), and prostaglandin E2 (PGE2) levels in patients with COVID-19. Serum concentrations of Gal-1, Gal-3, and PGE2 were measured using enzyme-linked immunosorbent assay on 84 patients with COVID-19 (severe = 29 and nonsevere = 55) and 56 healthy controls. In this study, increased levels of Gal-1 (median, 9.86, 6.35, and 3.67 ng/mL), Gal-3 (median, 415.31, 326.33, and 243.13 pg/mL), and PGE2 (median, 193.17, 192.58, and 124.62 pg/mL) levels were found in patients with COVID-19 than in healthy controls (P < 0.001 for all). In the severe disease group, Gal-3 levels were higher, while no differences were noted in Gal-1 and PGE2 levels (P = 0.011, P = 0.263, and P = 0.921, respectively). Serum levels of Gal-1 were positively correlated with those of Gal-3 (P = 0.871 and P < 0.001). Gal-3, C-reactive protein, lymphocyte count, and age were found as independent predictors of disease severity (P = 0.002, P = 0.001, P = 0.007, and P = 0.003, respectively). With the emergence of effective drug needs in the COVID-19 pandemic, differentiation of severe disease is important. Therefore, Gal-3 could be a potential prognostic biomarker of COVID-19.


Subject(s)
COVID-19 , Dinoprostone/blood , Galectin 1/blood , Galectin 3/blood , Biomarkers/blood , COVID-19/blood , Case-Control Studies , Humans , Pandemics
6.
Surg Endosc ; 35(6): 2981-2985, 2021 06.
Article in English | MEDLINE | ID: covidwho-1453742

ABSTRACT

INTRODUCTION: Stray energy transfer from surgical monopolar radiofrequency energy instruments can cause unintended thermal injuries during laparoscopic surgery. Single-incision laparoscopic surgery transfers more stray energy than traditional laparoscopic surgery. There is paucity of published data concerning stray energy during single-incision robotic surgery. The purpose of this study was to quantify stray energy transfer during traditional, multiport robotic surgery (TRS) compared to single-incision robotic surgery (SIRS). METHODS: An in vivo porcine model was used to simulate a multiport or single-incision robotic cholecystectomy (DaVinci Si, Intuitive Surgical, Sunnyvale, CA). A 5 s, open air activation of the monopolar scissors was done on 30 W and 60 W coag mode (ForceTriad, Covidien-Medtronic, Boulder, CO) and Swift Coag effect 3, max power 180 W (VIO 300D, ERBE USA, Marietta, GA). Temperature of the tissue (°C) adjacent to the tip of the assistant grasper or the camera was measured with a thermal camera (E95, FLIR Systems, Wilsonville, OR) to quantify stray energy transfer. RESULTS: Stray energy transfer was greater in the SIRS setup compared to TRS setup at the assistant grasper (11.6 ± 3.3 °C vs. 8.4 ± 1.6 °C, p = 0.013). Reducing power from 60 to 30 W significantly reduced stray energy transfer in SIRS (15.3 ± 3.4 °C vs. 11.6 ± 3.3 °C, p = 0.023), but not significantly for TRS (9.4 ± 2.5 °C vs. 8.4 ± 1.6 °C, p = 0.278). The use of a constant voltage regulating generator also minimized stray energy transfer for both SIRS (0.7 ± 0.4 °C, p < 0.001) and TRS (0.7 ± 0.4 °C, p < 0.001). CONCLUSIONS: More stray energy transfer occurs during single-incision robotic surgery than multiport robotic surgery. Utilizing a constant voltage regulating generator minimized stray energy transfer for both setups. These data can be used to guide robotic surgeons in their use of safe, surgical energy.


Subject(s)
Laparoscopy , Robotic Surgical Procedures , Robotics , Surgical Wound , Animals , Energy Transfer , Swine
7.
Med Sci Monit ; 26: e922281, 2020 Mar 31.
Article in English | MEDLINE | ID: covidwho-1453382

ABSTRACT

BACKGROUND Acute respiratory distress syndrome (ARDS) is a sudden and serious disease with increasing morbidity and mortality rates. Phosphodiesterase 4 (PDE4) is a novel target for inflammatory disease, and ibudilast (IBU), a PDE4 inhibitor, inhibits inflammatory response. Our study investigated the effect of IBU on the pathogenesis of neonatal ARDS and the underlying mechanism related to it. MATERIAL AND METHODS Western blotting was performed to analyze the expression levels of PDE4, CXCR4, SDF-1, CXCR5, CXCL1, inflammatory cytokines, and proteins related to cell apoptosis. Hematoxylin-eosin staining was performed to observe the pathological morphology of lung tissue. Pulmonary edema score was used to assess the degree of lung water accumulation after pulmonary injury. Enzyme-linked immunosorbent assay (ELISA) was used to assess levels of inflammatory factors (TNF-alpha, IL-1ß, IL-6, and MCP-1) in serum. TUNEL assay was used to detect apoptotic cells. RESULTS Increased expression of PDE4 was observed in an LPS-induced neonatal ARDS mouse model, and IBU ameliorated LPS-induced pathological manifestations and pulmonary edema in lung tissue. In addition, IBU attenuated the secretion of inflammatory cytokines by inactivating the chemokine axis in the LPS-induced neonatal ARDS mouse model. Finally, IBU significantly reduced LPS-induced cell apoptosis in lung tissue. CONCLUSIONS IBU, a PDE4 inhibitor, protected against ARDS by interfering with pulmonary inflammation and apoptosis. Our findings provide a novel and promising strategy to regulate pulmonary inflammation in ARDS.


Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Inflammation/drug therapy , Phosphodiesterase 4 Inhibitors/pharmacology , Pyridines/pharmacology , Respiratory Distress Syndrome, Newborn/drug therapy , Animals , Animals, Newborn , Apoptosis/drug effects , Apoptosis/immunology , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Humans , Inflammation/diagnosis , Inflammation/immunology , Inflammation/pathology , Injections, Intraperitoneal , Lipopolysaccharides/immunology , Lung/drug effects , Lung/immunology , Lung/pathology , Mice , Phosphodiesterase 4 Inhibitors/therapeutic use , Pyridines/therapeutic use , Respiratory Distress Syndrome, Newborn/diagnosis , Respiratory Distress Syndrome, Newborn/immunology , Respiratory Distress Syndrome, Newborn/pathology , Signal Transduction/drug effects , Signal Transduction/immunology
8.
Curr Top Microbiol Immunol ; 426: 21-43, 2020.
Article in English | MEDLINE | ID: covidwho-1451909

ABSTRACT

Pulmonary respiration inevitably exposes the mucosal surface of the lung to potentially noxious stimuli, including pathogens, allergens, and particulates, each of which can trigger pulmonary damage and inflammation. As inflammation resolves, B and T lymphocytes often aggregate around large bronchi to form inducible Bronchus-Associated Lymphoid Tissue (iBALT). iBALT formation can be initiated by a diverse array of molecular pathways that converge on the activation and differentiation of chemokine-expressing stromal cells that serve as the scaffolding for iBALT and facilitate the recruitment, retention, and organization of leukocytes. Like conventional lymphoid organs, iBALT recruits naïve lymphocytes from the blood, exposes them to local antigens, in this case from the airways, and supports their activation and differentiation into effector cells. The activity of iBALT is demonstrably beneficial for the clearance of respiratory pathogens; however, it is less clear whether it dampens or exacerbates inflammatory responses to non-infectious agents. Here, we review the evidence regarding the role of iBALT in pulmonary immunity and propose that the final outcome depends on the context of the disease.


Subject(s)
Bronchi/immunology , Immunity, Mucosal/immunology , Respiration/immunology , Humans , Lymphocytes/immunology
9.
EMBO Rep ; 22(6): e52744, 2021 06 04.
Article in English | MEDLINE | ID: covidwho-1389837

ABSTRACT

Severe cases of SARS-CoV-2 infection are characterized by hypercoagulopathies and systemic endotheliitis of the lung microvasculature. The dynamics of vascular damage, and whether it is a direct consequence of endothelial infection or an indirect consequence of an immune cell-mediated cytokine storm remain unknown. Using a vascularized lung-on-chip model, we find that infection of alveolar epithelial cells leads to limited apical release of virions, consistent with reports of monoculture infection. However, viral RNA and proteins are rapidly detected in underlying endothelial cells, which are themselves refractory to apical infection in monocultures. Although endothelial infection is unproductive, it leads to the formation of cell clusters with low CD31 expression, a progressive loss of barrier integrity and a pro-coagulatory microenvironment. Viral RNA persists in individual cells generating an inflammatory response, which is transient in epithelial cells but persistent in endothelial cells and typified by IL-6 secretion even in the absence of immune cells. Inhibition of IL-6 signalling with tocilizumab reduces but does not prevent loss of barrier integrity. SARS-CoV-2-mediated endothelial cell damage thus occurs independently of cytokine storm.


Subject(s)
COVID-19 , SARS-CoV-2 , Cytokine Release Syndrome , Endothelial Cells , Humans , Lung
10.
Sci Adv ; 7(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1388432

ABSTRACT

Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.


Subject(s)
Antiviral Agents/pharmacology , Azetidines/pharmacology , COVID-19/mortality , Enzyme Inhibitors/pharmacology , Janus Kinases/antagonists & inhibitors , Liver/virology , Purines/pharmacology , Pyrazoles/pharmacology , SARS-CoV-2/pathogenicity , Sulfonamides/pharmacology , Adult , Aged , Aged, 80 and over , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/virology , Cytokine Release Syndrome , Cytokines/metabolism , Drug Evaluation, Preclinical , Female , Gene Expression Profiling , Humans , Interferon alpha-2/metabolism , Italy , Janus Kinases/metabolism , Liver/drug effects , Male , Middle Aged , Patient Safety , Platelet Activation , Proportional Hazards Models , RNA-Seq , Spain , Virus Internalization/drug effects
11.
Mar Drugs ; 19(1)2020 Dec 24.
Article in English | MEDLINE | ID: covidwho-1389434

ABSTRACT

Compromised lung function is a feature of both infection driven and non-infective pathologies. Viral infections-including the current pandemic strain SARS-CoV-2-that affect lung function can cause both acute and long-term chronic damage. SARS-CoV-2 infection suppresses innate immunity and promotes an inflammatory response. Targeting these aspects of SARS-CoV-2 is important as the pandemic affects greater proportions of the population. In clinical and animal studies, fucoidans have been shown to increase innate immunity and decrease inflammation. In addition, dietary fucoidan has been shown to attenuate pulmonary damage in a model of acute viral infection. Direct inhibition of SARS-CoV-2 in vitro has been described, but is not universal. This short review summarizes the current research on fucoidan with regard to viral lung infections and lung damage.


Subject(s)
COVID-19/drug therapy , Lung/drug effects , Polysaccharides/pharmacology , SARS-CoV-2 , Animals , COVID-19/immunology , Humans , Lung/physiology , Lung Diseases/drug therapy , Polysaccharides/therapeutic use , Virus Diseases/drug therapy
12.
Respir Res ; 21(1): 154, 2020 Jun 18.
Article in English | MEDLINE | ID: covidwho-1331943

ABSTRACT

Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChRα7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRα7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRα7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRα7 in a sex-dependent manner.


Subject(s)
Coronavirus Infections/epidemiology , Electronic Nicotine Delivery Systems , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Pneumonia/metabolism , Vaping/adverse effects , alpha7 Nicotinic Acetylcholine Receptor/genetics , Angiotensin-Converting Enzyme 2 , Animals , Blood Gas Analysis , Blotting, Western , Bronchoalveolar Lavage Fluid , COVID-19 , Cytokines/analysis , Disease Models, Animal , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Pandemics , Pneumonia/physiopathology , Random Allocation , Reference Values , Role , Severe Acute Respiratory Syndrome/epidemiology , Signal Transduction/genetics
13.
Genes Immun ; 22(3): 141-160, 2021 07.
Article in English | MEDLINE | ID: covidwho-1275909

ABSTRACT

When surveying the current literature on COVID-19, the "cytokine storm" is considered to be pathogenetically involved in its severe outcomes such as acute respiratory distress syndrome, systemic inflammatory response syndrome, and eventually multiple organ failure. In this review, the similar role of DAMPs is addressed, that is, of those molecules, which operate upstream of the inflammatory pathway by activating those cells, which ultimately release the cytokines. Given the still limited reports on their role in COVID-19, the emerging topic is extended to respiratory viral infections with focus on influenza. At first, a brief introduction is given on the function of various classes of activating DAMPs and counterbalancing suppressing DAMPs (SAMPs) in initiating controlled inflammation-promoting and inflammation-resolving defense responses upon infectious and sterile insults. It is stressed that the excessive emission of DAMPs upon severe injury uncovers their fateful property in triggering dysregulated life-threatening hyperinflammatory responses. Such a scenario may happen when the viral load is too high, for example, in the respiratory tract, "forcing" many virus-infected host cells to decide to commit "suicidal" regulated cell death (e.g., necroptosis, pyroptosis) associated with release of large amounts of DAMPs: an important topic of this review. Ironically, although the aim of this "suicidal" cell death is to save and restore organismal homeostasis, the intrinsic release of excessive amounts of DAMPs leads to those dysregulated hyperinflammatory responses-as typically involved in the pathogenesis of acute respiratory distress syndrome and systemic inflammatory response syndrome in respiratory viral infections. Consequently, as briefly outlined in this review, these molecules can be considered valuable diagnostic and prognostic biomarkers to monitor and evaluate the course of the viral disorder, in particular, to grasp the eventual transition precociously from a controlled defense response as observed in mild/moderate cases to a dysregulated life-threatening hyperinflammatory response as seen, for example, in severe/fatal COVID-19. Moreover, the pathogenetic involvement of these molecules qualifies them as relevant future therapeutic targets to prevent severe/ fatal outcomes. Finally, a theory is presented proposing that the superimposition of coronavirus-induced DAMPs with non-virus-induced DAMPs from other origins such as air pollution or high age may contribute to severe and fatal courses of coronavirus pneumonia.


Subject(s)
Alarmins/immunology , COVID-19/immunology , Cytokine Release Syndrome/immunology , Respiratory Distress Syndrome/immunology , SARS-CoV-2/immunology , Virus Diseases/immunology , Alarmins/metabolism , COVID-19/metabolism , COVID-19/virology , Cytokine Release Syndrome/metabolism , Cytokines/immunology , Cytokines/metabolism , Humans , Inflammation/immunology , Inflammation/metabolism , Models, Immunological , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/metabolism , SARS-CoV-2/physiology , Virus Diseases/complications , Virus Diseases/metabolism
14.
Psychiatry Investig ; 18(6): 505-512, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1271097

ABSTRACT

OBJECTIVE: The whole world is still struggling with the COVID-19 pandemic. Inflammation response, thought to be associated with severe illness and death, is an important research topic in COVID-19. Inflammation is also an essential condition explored in psychiatric illnesses. Our knowledge about the relationship between the inflammation response and psychiatric comorbidities in patients with COVID-19 is very limited. In this study, the relationship between anxiety and depression levels and inflammation response of patients with COVID-19 hospitalized in the hospital was examined. METHODS: 175 patients were included in the study. Sociodemographic Data Form, Beck Depression Inventory and Beck Anxiety Inventory were applied to the patients. To evaluate the inflammation responses, blood sedimentation rate, C-reactive protein (CRP), procalcitonin, ferritin, neutrophil/lymphocyte ratio (NLR), and IL-6 levels were examined. RESULTS: In our study, no relationship was found between anxiety and depression levels and inflammatory responses in patients hospitalized with a diagnosis of COVID-19. Anxiety and depression levels of women were higher than men, and NLR, ferritin, IL-6 levels were found to be lower than men. Anxiety levels increase with age. There is a positive correlation between NLR and ferritin levels and duration of hospitalization. CONCLUSION: Our study examining the relationship of psychiatric comorbidities with the inflammation response and our increasing literature knowledge, together with studies evaluating the mental effects of COVID-19, suggest that determining the relationship between inflammation responses and psychiatric comorbidities in COVID-19, whose pathophysiology has not been clarified yet, maybe an essential step in interventions on the course of the disease.

15.
Front Immunol ; 12: 665329, 2021.
Article in English | MEDLINE | ID: covidwho-1268251

ABSTRACT

Infection by novel coronavirus SARS-CoV-2 causes different presentations of COVID-19 and some patients may progress to a critical, fatal form of the disease that requires their admission to ICU and invasive mechanical ventilation. In order to predict in advance which patients could be more susceptible to develop a critical form of COVID-19, it is essential to define the most adequate biomarkers. In this study, we analyzed several parameters related to the cellular immune response in blood samples from 109 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centers in Madrid, Spain, during the first pandemic peak between April and June 2020. Hospitalized patients with the most severe forms of COVID-19 showed a potent inflammatory response that was not translated into an efficient immune response. Despite the high levels of effector cytotoxic cell populations such as NK, NKT and CD8+ T cells, they displayed immune exhaustion markers and poor cytotoxic functionality against target cells infected with pseudotyped SARS-CoV-2 or cells lacking MHC class I molecules. Moreover, patients with critical COVID-19 showed low levels of the highly cytotoxic TCRγδ+ CD8+ T cell subpopulation. Conversely, CD4 count was greatly reduced in association to high levels of Tregs, low plasma IL-2 and impaired Th1 differentiation. The relative importance of these immunological parameters to predict COVID-19 severity was analyzed by Random Forest algorithm and we concluded that the most important features were related to an efficient cytotoxic response. Therefore, efforts to fight against SARS-CoV-2 infection should be focused not only to decrease the disproportionate inflammatory response, but also to elicit an efficient cytotoxic response against the infected cells and to reduce viral replication.


Subject(s)
COVID-19/epidemiology , COVID-19/immunology , Cytotoxicity, Immunologic , Intensive Care Units , Leukocytes, Mononuclear/immunology , Patient Admission/statistics & numerical data , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , Biomarkers , COVID-19/diagnosis , COVID-19/virology , Comorbidity , Cytokines/metabolism , Female , Humans , Immunophenotyping , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Severity of Illness Index , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
16.
Adv Food Nutr Res ; 96: 417-429, 2021.
Article in English | MEDLINE | ID: covidwho-1265623

ABSTRACT

Selenium (Se) is an element commonly found in the environment at different levels. Its compounds are found in soil, water, and air. This element is also present in raw materials of plant and animal origin, so it can be introduced into human organisms through food. Selenium is a cofactor of enzymes responsible for the antioxidant protection of the body and plays an important role in regulating inflammatory processes in the body. A deficiency in selenium is associated with a number of viral diseases, including COVID-19. This element, taken in excess, may have a toxic effect in the form of joint diseases and diseases of the blood system. Persistent selenium deficiency in the body may also impact infertility, and in such cases supplementation is needed.


Subject(s)
COVID-19/blood , Nutritional Status , Selenium/blood , COVID-19/etiology , Female , Humans , Infertility/blood , Infertility/drug therapy , Infertility/etiology , Male , Selenium/deficiency , Selenium/therapeutic use , Selenium/toxicity , Virus Diseases/blood , Virus Diseases/etiology
17.
Eur Rev Med Pharmacol Sci ; 25(10): 3772-3790, 2021 05.
Article in English | MEDLINE | ID: covidwho-1264762

ABSTRACT

Multiple epidemiological studies have suggested that industrialization and progressive urbanization should be considered one of the main factors responsible for the rising of atherosclerosis in the developing world. In this scenario, the role of trace metals in the insurgence and progression of atherosclerosis has not been clarified yet. In this paper, the specific role of selected trace elements (magnesium, zinc, selenium, iron, copper, phosphorus, and calcium) is described by focusing on the atherosclerotic prevention and pathogenesis plaque. For each element, the following data are reported: daily intake, serum levels, intra/extracellular distribution, major roles in physiology, main effects of high and low levels, specific roles in atherosclerosis, possible interactions with other trace elements, and possible influences on plaque development. For each trace element, the correlations between its levels and clinical severity and outcome of COVID-19 are discussed. Moreover, the role of matrix metalloproteinases, a family of zinc-dependent endopeptidases, as a new medical therapeutical approach to atherosclerosis is discussed. Data suggest that trace element status may influence both atherosclerosis insurgence and plaque evolution toward a stable or an unstable status. However, significant variability in the action of these traces is evident: some - including magnesium, zinc, and selenium - may have a protective role, whereas others, including iron and copper, probably have a multi-faceted and more complex role in the pathogenesis of the atherosclerotic plaque. Finally, calcium and phosphorus are implicated in the calcification of atherosclerotic plaques and in the progression of the plaque toward rupture and severe clinical complications. In particular, the role of calcium is debated. Focusing on the COVID-19 pandemia, optimized magnesium and zinc levels are indicated as important protective tools against a severe clinical course of the disease, often related to the ability of SARS-CoV-2 to cause a systemic inflammatory response, able to transform a stable plaque into an unstable one, with severe clinical complications.


Subject(s)
Atherosclerosis/pathology , Trace Elements/metabolism , Atherosclerosis/metabolism , COVID-19/pathology , COVID-19/virology , Calcium/blood , Calcium/metabolism , Copper/blood , Copper/metabolism , Humans , Iron/blood , Iron/metabolism , Magnesium/blood , Magnesium/metabolism , Matrix Metalloproteinases/metabolism , Phosphorus/blood , Phosphorus/metabolism , Risk , SARS-CoV-2/isolation & purification , Selenium/blood , Selenium/metabolism , Severity of Illness Index , Trace Elements/blood , Zinc/blood , Zinc/metabolism
18.
J Infect Dev Ctries ; 15(5): 630-638, 2021 05 31.
Article in English | MEDLINE | ID: covidwho-1262629

ABSTRACT

INTRODUCTION: Viral infections have been described as triggers for Kawasaki Disease (KD), a medium vessel vasculitis that affects young children. Akin to the H1N1 pandemic in 2009, there is a similar rise in the incidence of KD in children affected with Coronavirus disease 2019 (COVID-19). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has been reported to induce an exaggerated systemic inflammatory response resulting in multi-organ involvement, particularly initiated with pulmonary parenchymal damage. This review article will discuss KD-like manifestations in COVID-19 patients in the pediatric cohort. METHODOLOGY: Search terms "Kawasaki" "COVID-19" "SARS-COV-2" "PIM-TS" and "MIS-C" were used to look for relevant articles in PubMed and Google Scholar published in the last 5 years. RESULTS: There is some evidence to suggest that SARS-CoV-2 stimulates dysfunctional and hyperactive immune reactions mimicking KD in young patients. CONCLUSIONS: Therapeutic options, both investigational and repurposed, include intravenous immunoglobulins, steroids and anticoagulation. More studies are required to evaluate the effectiveness of these treatment options.


Subject(s)
COVID-19/complications , Mucocutaneous Lymph Node Syndrome , Child , Humans , Immunoglobulins, Intravenous/therapeutic use , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/physiopathology , Mucocutaneous Lymph Node Syndrome/virology , SARS-CoV-2
19.
Drugs Today (Barc) ; 57(5): 347-357, 2021 May.
Article in English | MEDLINE | ID: covidwho-1261291

ABSTRACT

Psoriasis is a chronic inflammatory disease that can be triggered by injury, trauma, infection and medications. Genetic and immunologic studies have highlighted the importance of the interleukin (IL)-23/T-helper 17 (Th17) pathway in systemic psoriasis pathogenesis. Main IL-23 is an upstream regulatory cytokine with direct effects on epidermal keratinocytes and other resident skin cells while IL-17, a downstream molecule, can activate inflammatory responses in different cells across a diversity of organs. Disease modification could be achieved with drugs that can slow down the biological processes that cause the persistent inflammation in moderate to severe psoriasis. Early intervention with anti-IL-17 and anti-IL-23 agents in new-onset moderate to severe plaque psoriasis might modify the natural course of the disease. Perhaps we are not simply seeing a pharmacologic and mechanistic effect of new-generation biologics but eventually a disease modification process. In this short report we underline the main available data which supports an important role for IL-17 blockade and address whether these new drugs targeting the IL-23/IL-17 axis could be disease-modifying agents in plaque psoriasis. This type of data gains more relevance in the current pandemic era, where chronic patients undergoing earlier treatment may have better outcomes and consequently avoid constant hospital visits.


Subject(s)
Biological Products , Psoriasis , Cytokines , Humans , Interleukin-17 , Psoriasis/drug therapy
20.
Front Physiol ; 12: 667024, 2021.
Article in English | MEDLINE | ID: covidwho-1247901

ABSTRACT

The kidnapping of the lipid metabolism of the host's cells by severe acute respiratory syndrome (SARS-CoV-2) allows the virus to transform the cells into optimal machines for its assembly and replication. Here we evaluated changes in the fatty acid (FA) profile and the participation of the activity of the desaturases, in plasma of patients with severe pneumonia by SARS-CoV-2. We found that SARS-CoV-2 alters the FA metabolism in the cells of the host. Changes are characterized by variations in the desaturases that lead to a decrease in total fatty acid (TFA), phospholipids (PL) and non-esterified fatty acids (NEFAs). These alterations include a decrease in palmitic and stearic acids (p ≤ 0.009) which could be used for the formation of the viral membranes and for the reparation of the host's own membrane. There is also an increase in oleic acid (OA; p = 0.001) which could modulate the inflammatory process, the cytokine release, apoptosis, necrosis, oxidative stress (OS). An increase in linoleic acid (LA) in TFA (p = 0.03) and a decreased in PL (p = 0.001) was also present. They result from damage of the internal mitochondrial membrane. The arachidonic acid (AA) percentage was elevated (p = 0.02) in the TFA and this can be participated in the inflammatory process. EPA was decreased (p = 0.001) and this may decrease of pro-resolving mediators with increase in the inflammatory process. The total of NEFAs (p = 0.03), PL (p = 0.001), cholesterol, HDL and LDL were decreased, and triglycerides were increased in plasma of the COVID-19 patients. Therefore, SARS-CoV-2 alters the FA metabolism, the changes are characterized by alterations in the desaturases that lead to variations in the TFA, PL, and NEFAs profiles. These changes may favor the replication of the virus but, at the same time, they are part of the defense system provided by the host cell metabolism in its eagerness to repair damage caused by the virus to cell membranes.

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