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1.
J Diabetes Complications ; 34(9): 107637, 2020 09.
Article in English | MEDLINE | ID: covidwho-1828813

ABSTRACT

BACKGROUND: The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS: A search using keywords "COVID-19" and "Diabetes" was performed using different sources, including PubMed and World Health Organization. RESULTS: COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute ß-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION: COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , COVID-19 , Humans , SARS-CoV-2
2.
J Leukoc Biol ; 111(2): 497-508, 2022 02.
Article in English | MEDLINE | ID: covidwho-1669515

ABSTRACT

Coronaviruses (CoVs) are RNA viruses that cause human respiratory infections. Zoonotic transmission of the SARS-CoV-2 virus caused the recent COVID-19 pandemic, which led to over 2 million deaths worldwide. Elevated inflammatory responses and cytotoxicity in the lungs are associated with COVID-19 severity in SARS-CoV-2-infected individuals. Bats, which host pathogenic CoVs, operate dampened inflammatory responses and show tolerance to these viruses with mild clinical symptoms. Delineating the mechanisms governing these host-specific inflammatory responses is essential to understand host-virus interactions determining the outcome of pathogenic CoV infections. Here, we describe the essential role of inflammasome activation in determining COVID-19 severity in humans and innate immune tolerance in bats that host several pathogenic CoVs. We further discuss mechanisms leading to inflammasome activation in human SARS-CoV-2 infection and how bats are molecularly adapted to suppress these inflammasome responses. We also report an analysis of functionally important residues of inflammasome components that provide new clues of bat strategies to suppress inflammasome signaling and innate immune responses. As spillover of bat viruses may cause the emergence of new human disease outbreaks, the inflammasome regulation in bats and humans likely provides specific strategies to combat the pathogenic CoV infections.


Subject(s)
COVID-19/pathology , Immune Tolerance , Immunity, Innate , Inflammasomes/immunology , SARS-CoV-2/immunology , Animals , COVID-19/immunology , COVID-19/virology , Chiroptera , Humans , Inflammasomes/metabolism , Phylogeny
3.
Front Immunol ; 12: 587146, 2021.
Article in English | MEDLINE | ID: covidwho-1574304

ABSTRACT

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a fast spreading virus leading to the development of Coronavirus Disease-2019 (COVID-19). Severe and critical cases are characterized by damage to the respiratory system, endothelial inflammation, and multiple organ failure triggered by an excessive production of proinflammatory cytokines, culminating in the high number of deaths all over the world. Sedentarism induces worse, continuous, and progressive consequences to health. On the other hand, physical activity provides benefits to health and improves low-grade systemic inflammation. The aim of this review is to elucidate the effects of physical activity in physical fitness, immune defense, and its contribution to mitigate the severe inflammatory response mediated by SARS-CoV-2. Physical exercise is an effective therapeutic strategy to mitigate the consequences of SARS-CoV-2 infection. In this sense, studies have shown that acute physical exercise induces the production of myokines that are secreted in tissues and into the bloodstream, supporting its systemic modulatory effect. Therefore, maintaining physical activity influence balance the immune system and increases immune vigilance, and also might promote potent effects against the consequences of infectious diseases and chronic diseases associated with the development of severe forms of COVID-19. Protocols to maintain exercise practice are suggested and have been strongly established, such as home-based exercise (HBE) and outdoor-based exercise (OBE). In this regard, HBE might help to reduce levels of physical inactivity, bed rest, and sitting time, impacting on adherence to physical activity, promoting all the benefits related to exercise, and attracting patients in different stages of treatment for COVID-19. In parallel, OBE must improve health, but also prevent and mitigate COVID-19 severe outcomes in all populations. In conclusion, HBE or OBE models can be a potent strategy to mitigate the progress of infection, and a coadjutant therapy for COVID-19 at all ages and different chronic conditions.


Subject(s)
COVID-19/immunology , Exercise , Healthy Lifestyle , SARS-CoV-2/physiology , Sedentary Behavior , Animals , Home Care Services , Humans , Physical Fitness , Social Isolation
4.
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
5.
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
6.
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
7.
Food Chem Toxicol ; 153: 112286, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1385569

ABSTRACT

Higher selenium status has been shown to improve the clinical outcome of infections caused by a range of evolutionally diverse viruses, including SARS-CoV-2. However, the impact of SARS-CoV-2 on host-cell selenoproteins remains elusive. The present study investigated the influence of SARS-CoV-2 on expression of selenoprotein mRNAs in Vero cells. SARS-CoV-2 triggered an inflammatory response as evidenced by increased IL-6 expression. Of the 25 selenoproteins, SARS-CoV-2 significantly suppressed mRNA expression of ferroptosis-associated GPX4, DNA synthesis-related TXNRD3 and endoplasmic reticulum-resident SELENOF, SELENOK, SELENOM and SELENOS. Computational analysis has predicted an antisense interaction between SARS-CoV-2 and TXNRD3 mRNA, which is translated with high efficiency in the lung. Here, we confirmed the predicted SARS-CoV-2/TXNRD3 antisense interaction in vitro using DNA oligonucleotides, providing a plausible mechanism for the observed mRNA knockdown. Inhibition of TXNRD decreases DNA synthesis which is thereby likely to increase the ribonucleotide pool for RNA synthesis and, accordingly, RNA virus production. The present findings provide evidence for a direct inhibitory effect of SARS-CoV-2 replication on the expression of a specific set of selenoprotein mRNAs, which merits further investigation in the light of established evidence for correlations between dietary selenium status and the outcome of SARS-CoV-2 infection.


Subject(s)
DNA/biosynthesis , Endoplasmic Reticulum Stress/physiology , Ferroptosis/physiology , RNA, Messenger/metabolism , SARS-CoV-2/physiology , Selenoproteins/metabolism , Animals , Chlorocebus aethiops , Gene Expression Regulation/physiology , RNA, Messenger/genetics , Selenoproteins/genetics , Vero Cells
8.
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
9.
PLoS One ; 16(6): e0252302, 2021.
Article in English | MEDLINE | ID: covidwho-1278172

ABSTRACT

A potent therapy for the infectious coronavirus disease COVID-19 is urgently required with, at the time of writing, research in this area still ongoing. This study aims to evaluate the in vitro anti-viral activities of combinations of certain commercially available drugs that have recently formed part of COVID-19 therapy. Dual combinatory drugs, namely; Lopinavir-Ritonavir (LOPIRITO)-Clarithromycin (CLA), LOPIRITO-Azithromycin (AZI), LOPIRITO-Doxycycline (DOXY), Hydroxychloroquine (HCQ)-AZI, HCQ-DOXY, Favipiravir (FAVI)-AZI, HCQ-FAVI, and HCQ-LOPIRITO, were prepared. These drugs were mixed at specific ratios and evaluated for their safe use based on the cytotoxicity concentration (CC50) values of human umbilical cord mesenchymal stem cells. The anti-viral efficacy of these combinations in relation to Vero cells infected with SARS-CoV-2 virus isolated from a patient in Universitas Airlangga hospital, Surabaya, Indonesia and evaluated for IC50 24, 48, and 72 hours after viral inoculation was subsequently determined. Observation of the viral load in qRT-PCR was undertaken, the results of which indicated the absence of high levels of cytotoxicity in any samples and that dual combinatory drugs produced lower cytotoxicity than single drugs. In addition, these combinations demonstrated considerable effectiveness in reducing the copy number of the virus at 48 and 72 hours, while even at 24 hours, post-drug incubation resulted in low IC50 values. Most combination drugs reduced pro-inflammatory markers, i.e. IL-6 and TNF-α, while increasing the anti-inflammatory response of IL-10. According to these results, the descending order of effective dual combinatory drugs is one of LOPIRITO-AZI>LOPIRITO-DOXY>HCQ-AZI>HCQ-FAVI>LOPIRITO-CLA>HCQ-DOX. It can be suggested that dual combinatory drugs, e.g. LOPIRITO-AZI, can potentially be used in the treatment of COVID-19 infectious diseases.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Hydroxychloroquine/pharmacology , SARS-CoV-2/drug effects , Animals , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/virology , Cell Survival/drug effects , Cells, Cultured , Chlorocebus aethiops , Drug Combinations , Hospitalization , Host-Pathogen Interactions/drug effects , Humans , Hydroxychloroquine/therapeutic use , Indonesia , Inhibitory Concentration 50 , Inpatients , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Time Factors , Vero Cells , Viral Load/drug effects
10.
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
11.
Am J Trop Med Hyg ; 104(5): 1611-1612, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1273618

ABSTRACT

COVID-19 can trigger a systemic inflammatory response that in some cases leads to severe lung involvement, multisystem dysfunction, and death. Dexamethasone therapy, because of its potent anti-inflammatory effects, has been proposed for the management of hospitalized patients with severe COVID-19. The subject of this article is to discuss potential strategies to tackle Strongyloides hyperinfection in hospitalized patients with COVID-19 receiving dexamethasone therapy in low- and middle-income countries. In this context, dexamethasone treatment has been found to be generally safe. However, its use in people coinfected with undetected Strongyloides stercoralis increases the risk for Strongyloides hyperinfection/dissemination a potentially fatal complication. Infection caused by S. stercoralis may remain asymptomatic or with mild symptoms in humans for several years. Early detection and specific treatment prevent a fatal evolution of this complication, but the challenge is to screen before corticosteroid therapy. In some cases, presumptive treatment may be justified. Ivermectin is the gold standard for treatment.


Subject(s)
COVID-19/drug therapy , Dexamethasone/adverse effects , SARS-CoV-2 , Strongyloides stercoralis , Strongyloidiasis/etiology , Animals , Developing Countries , Strongyloidiasis/drug therapy
12.
Cardiovasc Res ; 117(10): 2148-2160, 2021 08 29.
Article in English | MEDLINE | ID: covidwho-1266112

ABSTRACT

The pandemic of coronavirus disease (COVID)-19 is a global threat, causing high mortality, especially in the elderly. The main symptoms and the primary cause of death are related to interstitial pneumonia. Viral entry also into myocardial cells mainly via the angiotensin converting enzyme type 2 (ACE2) receptor and excessive production of pro-inflammatory cytokines, however, also make the heart susceptible to injury. In addition to the immediate damage caused by the acute inflammatory response, the heart may also suffer from long-term consequences of COVID-19, potentially causing a post-pandemic increase in cardiac complications. Although the main cause of cardiac damage in COVID-19 remains coagulopathy with micro- (and to a lesser extent macro-) vascular occlusion, open questions remain about other possible modalities of cardiac dysfunction, such as direct infection of myocardial cells, effects of cytokines storm, and mechanisms related to enhanced coagulopathy. In this opinion paper, we focus on these lesser appreciated possibilities and propose experimental approaches that could provide a more comprehensive understanding of the cellular and molecular bases of cardiac injury in COVID-19 patients. We first discuss approaches to characterize cardiac damage caused by possible direct viral infection of cardiac cells, followed by formulating hypotheses on how to reproduce and investigate the hyperinflammatory and pro-thrombotic conditions observed in the heart of COVID-19 patients using experimental in vitro systems. Finally, we elaborate on strategies to discover novel pathology biomarkers using omics platforms.


Subject(s)
COVID-19/virology , Heart Diseases/virology , Heart/virology , Myocytes, Cardiac/virology , SARS-CoV-2/pathogenicity , Animals , Biomarkers/metabolism , Blood Coagulation , COVID-19/complications , Fibrosis , Heart/physiopathology , Heart Diseases/metabolism , Heart Diseases/pathology , Heart Diseases/physiopathology , Host-Pathogen Interactions , Humans , Inflammation Mediators/metabolism , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Ventricular Remodeling
13.
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
14.
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
15.
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
16.
Genes (Basel) ; 12(6)2021 05 28.
Article in English | MEDLINE | ID: covidwho-1256476

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. AIM: We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like-1 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses. METHODS: 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis. RESULTS: There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively (p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease. CONCLUSION: Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.


Subject(s)
COVID-19/genetics , COVID-19/virology , Discoidin Domain Receptor 1/genetics , Genetic Predisposition to Disease , Interferons/genetics , Polymorphism, Single Nucleotide , SARS-CoV-2/physiology , Tolloid-Like Metalloproteinases/genetics , Alleles , Biomarkers , COVID-19/diagnosis , COVID-19/immunology , Case-Control Studies , Comorbidity , Cytokines/metabolism , Female , Genotype , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate , Male , Prognosis , Severity of Illness Index , Viral Load
17.
Front Immunol ; 12: 671013, 2021.
Article in English | MEDLINE | ID: covidwho-1247865

ABSTRACT

The impact of Covid-19 pneumonia caused by SARS-CoV-2 on transplanted populations under chronic immunosuppression seems to be greater than in normal population. Clinical management of the disease, particularly in those patients worsening after a cytokine storm, with or without allograft impairment and using available therapeutic approaches in the absence of specific drugs to fight against the virus, involves a major challenge for physicians. We herein provide evidence of the usefulness of high-dose intravenous immunoglobulin (IVIG) combined with steroid pulses to successfully treat a case of Covid-19 pneumonia in a single-kidney transplanted patient with mechanical ventilation and hemodialysis requirements in the setting of a cytokine storm. A rapid decrease in the serum level of inflammatory cytokines, particularly IL-6, IL-8, TNF-α, MCP-1 and IL-10, as well as of acute-phase reactants such as ferritin, D-dimer and C-reactive protein was observed after the IVIG infusion and methylprednisolone bolus administration with a parallel clinical improvement and progressive allograft function recovery, allowing the patient's final discharge 40 days after the treatment onset. The immunomodulatory effect of IVIG together with the anti-inflammatory and immunosuppressive potential of steroids could be an alternative strategy to treat severe cases of Covid-19 pneumonia associated with an uncontrolled inflammatory response in transplanted populations.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Graft Rejection/drug therapy , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/therapy , Kidney Transplantation , SARS-CoV-2/physiology , Steroids/therapeutic use , Transplant Recipients , Acute Disease , COVID-19/complications , Disease Progression , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Renal Dialysis , Respiration, Artificial , Transplantation, Homologous
18.
Cureus ; 13(5): e14813, 2021 May 03.
Article in English | MEDLINE | ID: covidwho-1244972

ABSTRACT

Infective endocarditis (IE) is associated with relatively high morbidity and mortality and several risk factors have been identified in the past. Several predisposing factors for IE have been recognized in the literature, depending on the type of bacteria. Coronavirus disease 2019 (COVID-19) infection causes coagulopathy-associated complications and damage to many organ systems due to the inflammatory response induced by this viral infection. COVID-19 emerged only about a year ago and there are many unknown post-COVID-19 complications at this time. Here, we present the case of Streptococcus mitis IE in a patient with no prior predisposing factors other than diagnosis with COVID-19 a month ago.

19.
Scand J Clin Lab Invest ; 81(4): 255-263, 2021 07.
Article in English | MEDLINE | ID: covidwho-1242057

ABSTRACT

Coronaviruses belonging to the Coronaviridae family are single-stranded RNA viruses. The entry of SARS-CoV-2 is accomplished via ACE-2 receptors. SARS-CoV-2 infection coactivates both innate and adaptive immune responses. Although SARS-CoV-2 stimulates antibody production with a typical pattern of IgM/IgG, cellular immunity is also impaired. In severe cases, low CD4 + and CD8 + T cell counts are associated with impaired immune functions, and high neutrophil/lymphocyte ratios accompanying low lymphocyte subsets have been demonstrated. Recently, high IFN -α/γ ratios with impaired T cell responses, and increased IL-1, IL-6, TNF-α, MCP-1, IP-10, IL-4, IL-10 have been reported in COVID-19 infection. Increased proinflammatory cytokines and chemokines in patients with severe COVID-19 may cause the suppression of CD4 + and CD8 + T cells and regulatory T cells, causing excessive inflammatory responses and fatal cytokine storm with tissue and organ damage. Consequently, novel therapeutics to be developed against host immune system, including blockade of cytokines (IL-6, IL-1, IFN) themselves, their receptors or signaling pathways- JAK inhibitors- could be effective as potential therapeutics.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/immunology , COVID-19/physiopathology , Adrenal Cortex Hormones/therapeutic use , Animals , Antiviral Agents/therapeutic use , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/virology , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Immunotherapy/methods , Macrophages/immunology , Macrophages/pathology , Macrophages/virology
20.
Clin Nutr ESPEN ; 43: 1-8, 2021 06.
Article in English | MEDLINE | ID: covidwho-1240256

ABSTRACT

BACKGROUND & AIMS: Maternal gestational infection is a well-characterized risk factor for offsprings' development of mental disorders including schizophrenia, autism, and attention deficit disorder. The inflammatory response elicited by the infection is partly directed against the placenta and fetus and is the putative pathogenic mechanism for fetal brain developmental abnormalities. Fetal brain abnormalities are generally irreversible after birth and increase risk for later mental disorders. Maternal immune activation in animals models this pathophysiology. SARS-CoV-2 produces maternal inflammatory responses during pregnancy similar to previously studied common respiratory viruses. METHOD: Choline, folic acid, Vitamin D, and n-3 polyunsaturated fatty acids are among the nutrients that have been studied as possible mitigating factors for effects of maternal infection and inflammation on fetal development. Clinical and animal studies relevant to their use in pregnant women who have been infected are reviewed. RESULTS: Higher maternal choline levels have positive effects on the development of brain function for infants of mothers who experienced viral infections in early pregnancy. No other nutrient has been studied in the context of viral inflammation. Vitamin D reduces pro-inflammatory cytokines in some, but not all, studies. Active folic acid metabolites decrease anti-inflammatory cytokines. N-3 polyunsaturated fatty acids have no effect. CONCLUSIONS: Vitamin D and folic acid are already supplemented in food additives and in prenatal vitamins. Despite recommendations by several public health agencies and medical societies, choline intake is often inadequate in early gestation when the brain is forming. A public health initiative for choline supplements during the pandemic could be helpful for women planning or already pregnant who also become exposed or infected with SARS-CoV-2.


Subject(s)
Brain , COVID-19/complications , Choline/therapeutic use , Fetal Development , Mothers , Nutritional Status , Pregnancy Complications, Infectious/virology , Animals , Brain/drug effects , COVID-19/metabolism , COVID-19/virology , Child Development/drug effects , Choline/pharmacology , Developmental Disabilities/etiology , Developmental Disabilities/prevention & control , Dietary Supplements , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/therapeutic use , Female , Fetal Development/drug effects , Fetus/drug effects , Folic Acid/pharmacology , Folic Acid/therapeutic use , Humans , Infant , Inflammation/complications , Inflammation/metabolism , Nutritional Requirements , Pandemics , Placenta/metabolism , Pregnancy , Pregnancy Complications, Infectious/metabolism , SARS-CoV-2 , Vitamin D/pharmacology , Vitamin D/therapeutic use
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