首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 0 毫秒
1.
    
The endothelium has a fundamental role in the cardiovascular complications of coronavirus disease 2019 (COVID-19). Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particularly affects endothelial cells. The virus binds to the angiotensin-converting enzyme 2 (ACE-2) receptor (present on type 2 alveolar cells, bronchial epithelial cells, and endothelial cells), and induces a cytokine storm. The cytokines tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 have particular effects on endothelial cells—leading to endothelial dysfunction, endothelial cell death, changes in tight junctions, and vascular hyperpermeability. Under normal conditions, apoptotic endothelial cells are removed into the bloodstream. During COVID-19, however, endothelial cells are detached more rapidly, and do not regenerate as effectively as usual. The loss of the endothelium on the luminal surface abolishes all of the vascular responses mediated by the endothelium and nitric oxide production in particular, which results in greater contractility. Moreover, circulating endothelial cells infected with SARS-CoV-2 act as vectors for viral dissemination by forming clusters that migrate into the circulation and reach distant organs. The cell clusters and the endothelial dysfunction might contribute to the various thromboembolic pathologies observed in COVID-19 by inducing the formation of intravascular microthrombi, as well as by triggering disseminated intravascular coagulation. Here, we review the contributions of endotheliopathy and endothelial-cell-derived extracellular vesicles to the pathogenesis of COVID-19, and discuss therapeutic strategies that target the endothelium in patients with COVID-19.  相似文献   

2.
    
In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention.  相似文献   

3.
    
SARS-CoV-2 infections are responsible for the COVID-19 pandemic. Transferrin has been found to explain the link between diseases associated with impaired iron transport and COVID-19 infection. The effect of SARS-CoV-2 on human whole blood was studied by differential scanning calorimetry. The analysis of the thermal transition curves showed that the melting temperature of the transferrin-related peak decreased in the presence of SARS-CoV-2. The ratio of the under-curve area of the two main peaks was greatly affected, while the total enthalpy of the heat denaturation remained nearly unchanged in the presence of the virus. These results indicate that SARS-CoV-2, through binding to transferrin, may influence its Fe3+ uptake by inducing thermodynamic changes. Therefore, transferrin may remain in an iron-free apo-conformational state, which depends on the SARS-CoV-2 concentration. SARS-CoV-2 can induce disturbance in erythropoiesis due to toxicity generated by free iron overload.  相似文献   

4.
    
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality worldwide. Though previous coronaviruses have caused substantial epidemics in recent years, effective therapies remained limited at the start of the Coronavirus disease 19 (COVID-19) pandemic. The emergence and rapid spread throughout the globe of the novel SARS-CoV-2 virus necessitated a rapid development of therapeutics. Given the multitude of therapies that have emerged over the last two years and the evolution of data surrounding the efficacy of these therapies, we aim to provide an update on the major clinical trials that influenced clinical utilization of various COVID-19 therapeutics. This review focuses on currently used therapies in the United States and discusses the molecular mechanisms by which these therapies target the SARS-CoV-2 virus or the COVID-19 disease process. PubMed and EMBASE were used to find trials assessing the efficacy of various COVID-19 therapies. The keywords SARS-CoV-2, COVID-19, and the names of the various therapies included in this review were searched in different combinations to find large-scale randomized controlled trials performed since the onset of the COVID-19 pandemic. Multiple therapeutic options are currently approved for the treatment of SARS-CoV-2 and prevention of severe disease in high-risk individuals in both in the inpatient and outpatient settings. In severe disease, a combination of antiviral and immunomodulatory treatments is currently recommended for treatment. Additionally, anti-viral agents have shown promise in preventing severe disease and hospitalization for those in the outpatient setting. More recently, current therapeutic approaches are directed toward early treatment with monoclonal antibodies directed against the SARS-CoV-2 virus. Despite this, no treatment to date serves as a definitive cure and vaccines against the SARS-CoV-2 virus remain our best defense to prevent further morbidity and mortality.  相似文献   

5.
    
This review article was designed to evaluate the existing evidence related to the molecular processes of SARS-CoV-2 infection in the oral cavity. The World Health Organization stated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission is produced by respiratory droplets and aerosols from the oral cavity of infected patients. The oral cavity structures, keratinized and non-keratinized mucosa, and salivary glands’ epithelia express SARS-CoV-2 entry and transmission factors, especially angiotensin converting enzyme Type 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Replication of the virus in cells leads to local and systemic infection spread, and cellular damage is associated with clinical signs and symptoms of the disease in the oral cavity. Saliva, both the cellular and acellular fractions, holds the virus particles and contributes to COVID-19 transmission. The review also presents information about the factors modifying SARS-CoV-2 infection potential and possible local pharmacotherapeutic interventions, which may confine SARS-CoV-2 virus entry and transmission in the oral cavity. The PubMed and Scopus databases were used to search for suitable keywords such as: SARS-CoV-2, COVID-19, oral virus infection, saliva, crevicular fluid, salivary gland, tongue, oral mucosa, periodontium, gingiva, dental pulp, ACE2, TMPRSS2, Furin, diagnosis, topical treatment, vaccine and related words in relevant publications up to 28 December 2021. Data extraction and quality evaluation of the articles were performed by two reviewers, and 63 articles were included in the final review.  相似文献   

6.
    
The new SARS-CoV-2 coronavirus is responsible for the COVID-19 pandemic. A massive vaccination campaign, which is still ongoing, has averted most serious consequences worldwide; however, lines of research are continuing to identify the best drug therapies to treat COVID-19 infection. SARS-CoV-2 penetrates the cells of the host organism through ACE2. The ACE2 protein plays a key role in the renin–angiotensin system (RAS) and undergoes changes in expression during different stages of COVID-19 infection. It appears that an unregulated RAS is responsible for the severe lung damage that occurs in some cases of COVID-19. Pharmacologically modifying the expression of ACE2 could be an interesting line of research to follow in order to avoid the severe complications of COVID-19.  相似文献   

7.
    
We assessed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in samples from 89 acute COVID-19 patients, utilizing blood samples collected during the first wave of COVID-19 in Italy. The goal of the study was to examine correlations between SARS-CoV-2-specific T cell responses in the early phase comparing mild, moderate, or severe COVID-19 disease outcomes. T cell responses to the spike (S) and non-S proteins were measured in a combined activation-induced marker (AIM) and intracellular cytokine staining (ICS) assay. Early CD4+ T cell responses to SARS-CoV-2 S correlated with milder disease by both AIM and IFNγ ICS readouts. The correlation of S-specific CD4+ T cell responses with milder disease severity was most striking within the first two weeks of symptom onset compared to later time points. Furthermore, donors with milder disease were associated with polyantigenic CD4+ T cell responses that recognized more prominently non-S proteins in addition to S, while severe acute COVID-19 was characterized by lower magnitudes of CD4+ T cell responses and a narrower repertoire. In conclusion, this study highlights that both the magnitude and breadth of early SARS-CoV-2-specific CD4+ T cell responses correlated with milder disease outcomes in acute COVID-19 patients.  相似文献   

8.
    
As of December 2021, SARS-CoV-2 had caused over 250 million infections and 5 million deaths worldwide. Furthermore, despite the development of highly effective vaccines, novel variants of SARS-CoV-2 continue to sustain the pandemic, and the search for effective therapies for COVID-19 remains as urgent as ever. Though the primary manifestation of COVID-19 is pneumonia, the disease can affect multiple organs, including the kidneys, with acute kidney injury (AKI) being among the most common extrapulmonary manifestations of severe COVID-19. In this article, we start by reflecting on the epidemiology of kidney disease in COVID-19, which overwhelmingly demonstrates that AKI is common in COVID-19 and is strongly associated with poor outcomes. We also present emerging data showing that COVID-19 may result in long-term renal impairment and delve into the ongoing debate about whether AKI in COVID-19 is mediated by direct viral injury. Next, we focus on the molecular pathogenesis of SARS-CoV-2 infection by both reviewing previously published data and presenting some novel data on the mechanisms of cellular viral entry. Finally, we relate these molecular mechanisms to a series of therapies currently under investigation and propose additional novel therapeutic targets for COVID-19.  相似文献   

9.
    
Recently, we have experienced a serious pandemic. Despite significant technological advances in molecular technologies, it is very challenging to slow down the infection spread. It appeared that due to globalization, SARS-CoV-2 spread easily and adapted to new environments or geographical or weather zones. Additionally, new variants are emerging that show different infection potential and clinical outcomes. On the other hand, we have some experience with other pandemics and some solutions in virus elimination that could be adapted. This is of high importance since, as the latest reports demonstrate, vaccine technology might not follow the new, mutated virus outbreaks. Thus, identification of novel strategies and markers or diagnostic methods is highly necessary. For this reason, we present some of the latest views on SARS-CoV-2/COVID-19 therapeutic strategies and raise a solution based on miRNA. We believe that in the face of the rapidly increasing global situation and based on analogical studies of other viruses, the possibility of using the biological potential of miRNA technology is very promising. It could be used as a promising diagnostic and prognostic factor, as well as a therapeutic target and tool.  相似文献   

10.
    
Although coronavirus disease 2019 (COVID-19)-related major health consequences involve the lungs, a growing body of evidence indicates that COVID-19 is not inert to the pancreas either. This review presents a summary of the molecular mechanisms involved in the development of pancreatic dysfunction during the course of COVID-19, the comparison of the effects of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pancreatic function, and a summary of how drugs used in COVID-19 treatment may affect this organ. It appears that diabetes is not only a condition that predisposes a patient to suffer from more severe COVID-19, but it may also develop as a consequence of infection with this virus. Some SARS-CoV-2 inpatients experience acute pancreatitis due to direct infection of the tissue with the virus or due to systemic multiple organ dysfunction syndrome (MODS) accompanied by elevated levels of amylase and lipase. There are also reports that reveal a relationship between the development and treatment of pancreatic cancer and SARS-CoV-2 infection. It has been postulated that evaluation of pancreatic function should be increased in post-COVID-19 patients, both adults and children.  相似文献   

11.
    
Inflammasome activation is one of the first steps in initiating innate immune responses. In this work, we studied the activation of inflammasomes in the airways of critically ill COVID-19 patients and the effects of N-acetylcysteine (NAC) on inflammasomes. Tracheal biopsies were obtained from critically ill patients without COVID-19 and no respiratory disease (control, n = 32), SARS-CoV-2 B.1 variant (n = 31), and B.1.1.7 VOC alpha variant (n = 20) patients. Gene expression and protein expression were measured by RT-qPCR and immunohistochemistry. Macrophages and bronchial epithelial cells were stimulated with different S, E, M, and N SARS-CoV-2 recombinant proteins in the presence or absence of NAC. NLRP3 inflammasome complex was over-expressed and activated in the COVID-19 B.1.1.7 VOC variant and associated with systemic inflammation and 28-day mortality. TLR2/MyD88 and redox NOX4/Nrf2 ratio were also over-expressed in the COVID-19 B.1.1.7 VOC variant. The combination of S-E-M SARS-CoV-2 recombinant proteins increased cytokine release in macrophages and bronchial epithelial cells through the activation of TLR2. NAC inhibited SARS-CoV-2 mosaic (S-E-M)-induced cytokine release and inflammasome activation. In summary, inflammasome is over-activated in severe COVID-19 and increased in B.1.1.7 VOC variant. In addition, NAC can reduce inflammasome activation induced by SARS-CoV-2 in vitro, which may be of potential translational value in COVID-19 patients.  相似文献   

12.
    
Hematological and hemorheological parameters are known to be altered in COVID-19; however, the value of combined monitoring in order to deduce disease severity is only scarcely examined. A total of 44 acute SARS-CoV-2-infected patients (aCOV) and 44 age-matched healthy controls (Con) were included. Blood of aCOV was sampled at admission (T0), and at day 2 (T2), day 5 (T5), day 10 (T10), and day 30 (T30) while blood of Con was only sampled once. Inter- and intra-group differences were calculated for hematological and hemorheological parameters. Except for mean cellular volume and mean cellular hemoglobin, all blood cell parameters were significantly different between aCOV and Con. During the acute disease state (T0–T5), hematological and hemorheological parameters were highly altered in aCOV; in particular, anemic conditions and increased immune cell response/inflammation, oxidative/nitrosative stress, decreased deformability, as well as increased aggregation, were observed. During treatment and convalescence until T30, almost all abnormal values of aCOV improved towards Con values. During the acute state of the COVID-19 disease, the hematological, as well as the hemorheological system, show fast and potentially pathological changes that might contribute to the progression of the disease, but changes appear to be largely reversible after four weeks. Measuring RBC deformability and aggregation, as well as oxidative stress induction, may be helpful in monitoring critically ill COVID-19 patients.  相似文献   

13.
    
Predicting SARS-CoV-2 mutations is difficult, but predicting recurrent mutations driven by the host, such as those caused by host deaminases, is feasible. We used machine learning to predict which positions from the SARS-CoV-2 genome will hold a recurrent mutation and which mutations will be the most recurrent. We used data from April 2021 that we separated into three sets: a training set, a validation set, and an independent test set. For the test set, we obtained a specificity value of 0.69, a sensitivity value of 0.79, and an Area Under the Curve (AUC) of 0.8, showing that the prediction of recurrent SARS-CoV-2 mutations is feasible. Subsequently, we compared our predictions with updated data from January 2022, showing that some of the false positives in our prediction model become true positives later on. The most important variables detected by the model’s Shapley Additive exPlanation (SHAP) are the nucleotide that mutates and RNA reactivity. This is consistent with the SARS-CoV-2 mutational bias pattern and the preference of some host deaminases for specific sequences and RNA secondary structures. We extend our investigation by analyzing the mutations from the variants of concern Alpha, Beta, Delta, Gamma, and Omicron. Finally, we analyzed amino acid changes by looking at the predicted recurrent mutations in the M-pro and spike proteins.  相似文献   

14.
    
Antibodies play a crucial role in the immune response, in fighting off pathogens as well as helping create strong immunological memory. Antibody-dependent enhancement (ADE) occurs when non-neutralising antibodies recognise and bind to a pathogen, but are unable to prevent infection, and is widely known and is reported as occurring in infection caused by several viruses. This narrative review explores the ADE phenomenon, its occurrence in viral infections and evaluates its role in infection by SARS-CoV-2 virus, which causes coronavirus disease 2019 (COVID-19). As of yet, there is no clear evidence of ADE in SARS-CoV-2, though this area is still subject to further study.  相似文献   

15.
    
The highly transmittable and infectious COVID-19 remains a major threat worldwide, with the elderly and comorbid individuals being the most vulnerable. While vaccines are currently available, therapeutic drugs will help ease the viral outbreak and prevent serious health outcomes. Epigenetic modifications regulate gene expression through changes in chromatin structure and have been linked to viral pathophysiology. Since epigenetic modifications contribute to the life cycle of the virus and host immune responses to infection, epigenetic drugs are promising treatment targets to ameliorate COVID-19. Deficiency of the multifunctional secosteroid hormone vitamin D is a global health threat. Vitamin D and its receptor function to regulate genes involved in immunity, apoptosis, proliferation, differentiation, and inflammation. Amassed evidence also indicates the biological relations of vitamin D with reduced disease risk, while its receptor can be modulated by epigenetic mechanisms. The immunomodulatory effects of vitamin D suggest a role for vitamin D as a COVID-19 therapeutic agent. Therefore, this review highlights the epigenetic effects on COVID-19 and vitamin D while also proposing a role for vitamin D in COVID-19 infections.  相似文献   

16.
    
A balanced and varied diet provides diverse beneficial effects on health, such as adequate micronutrient availability and a gut microbiome in homeostasis. Besides their participation in biochemical processes as cofactors and coenzymes, vitamins and minerals have an immunoregulatory function; meanwhile, gut microbiota and its metabolites coordinate directly and indirectly the cell response through the interaction with the host receptors. Malnourishment is a crucial risk factor for several pathologies, and its involvement during the Coronavirus Disease 2019 pandemic has been reported. This pandemic has caused a significant decline in the worldwide population, especially those with chronic diseases, reduced physical activity, and elder age. Diet and gut microbiota composition are probable causes for this susceptibility, and its supplementation can play a role in reestablishing microbial homeostasis and improving immunity response against Coronavirus Disease 2019 infection and recovery. This study reviews the role of micronutrients and microbiomes in the risk of infection, the severity of disease, and the Coronavirus Disease 2019 sequelae.  相似文献   

17.
    
(1) Background: In COVID-19 survivors there is an increased prevalence of pulmonary fibrosis of which the underlying molecular mechanisms are poorly understood; (2) Methods: In this multicentric study, n = 12 patients who succumbed to COVID-19 due to progressive respiratory failure were assigned to an early and late group (death within ≤7 and >7 days of hospitalization, respectively) and compared to n = 11 healthy controls; mRNA and protein expression as well as biological pathway analysis were performed to gain insights into the evolution of pulmonary fibrogenesis in COVID-19; (3) Results: Median duration of hospitalization until death was 3 (IQR25-75, 3–3.75) and 14 (12.5–14) days in the early and late group, respectively. Fifty-eight out of 770 analyzed genes showed a significantly altered expression signature in COVID-19 compared to controls in a time-dependent manner. The entire study group showed an increased expression of BST2 and IL1R1, independent of hospitalization time. In the early group there was increased activity of inflammation-related genes and pathways, while fibrosis-related genes (particularly PDGFRB) and pathways dominated in the late group; (4) Conclusions: After the first week of hospitalization, there is a shift from pro-inflammatory to fibrogenic activity in severe COVID-19. IL1R1 and PDGFRB may serve as potential therapeutic targets in future studies.  相似文献   

18.
    
The non-classical histocompatibility antigen G (HLA-G) is an immune checkpoint molecule that has been implicated in viral disorders. We evaluated the plasma soluble HLA-G (sHLA-G) in 239 individuals, arranged in COVID-19 patients (n = 189) followed up at home or in a hospital, and in healthy controls (n = 50). Increased levels of sHLA-G were observed in COVID-19 patients irrespective of the facility care, gender, age, and the presence of comorbidities. Compared with controls, the sHLA-G levels increased as far as disease severity progressed; however, the levels decreased in critically ill patients, suggesting an immune exhaustion phenomenon. Notably, sHLA-G exhibited a positive correlation with other mediators currently observed in the acute phase of the disease, including IL-6, IL-8 and IL-10. Although sHLA-G levels may be associated with an acute biomarker of COVID-19, the increased levels alone were not associated with disease severity or mortality due to COVID-19. Whether the SARS-CoV-2 per se or the innate/adaptive immune response against the virus is responsible for the increased levels of sHLA-G are questions that need to be further addressed.  相似文献   

19.
    
The Coronavirus Disease 2019 (COVID-19) pandemic has become a global health emergency with no effective medical treatment and with incipient vaccines. It is caused by a new positive-sense RNA virus called severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). G-quadruplexes (G4s) are nucleic acid secondary structures involved in the control of a variety of biological processes including viral replication. Using several G4 prediction tools, we identified highly putative G4 sequences (PQSs) within the positive-sense (+gRNA) and negative-sense (−gRNA) RNA strands of SARS-CoV-2 conserved in related betacoronaviruses. By using multiple biophysical techniques, we confirmed the formation of two G4s in the +gRNA and provide the first evidence of G4 formation by two PQSs in the −gRNA of SARS-CoV-2. Finally, biophysical and molecular approaches were used to demonstrate for the first time that CNBP, the main human cellular protein bound to SARS-CoV-2 RNA genome, binds and promotes the unfolding of G4s formed by both strands of SARS-CoV-2 RNA genome. Our results suggest that G4s found in SARS-CoV-2 RNA genome and its negative-sense replicative intermediates, as well as the cellular proteins that interact with them, are relevant factors for viral genes expression and replication cycle, and may constitute interesting targets for antiviral drugs development.  相似文献   

20.
    
The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin–angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号