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1.
Shock ; 57(1): 1-6, 2022 01 01.
Статья в английский | MEDLINE | ID: covidwho-2191212

Реферат

BACKGROUND: The pathomechanisms of hypoxemia and treatment strategies for type H and type L acute respiratory distress syndrome (ARDS) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) have not been elucidated. MAIN TEXT: SARS-CoV-2 mainly targets the lungs and blood, leading to ARDS, and systemic thrombosis or bleeding. Angiotensin II-induced coagulopathy, SARS-CoV-2-induced hyperfibrin(ogen)olysis, and pulmonary and/or disseminated intravascular coagulation due to immunothrombosis contribute to COVID-19-associated coagulopathy. Type H ARDS is associated with hypoxemia due to diffuse alveolar damage-induced high right-to-left shunts. Immunothrombosis occurs at the site of infection due to innate immune inflammatory and coagulofibrinolytic responses to SARS-CoV-2, resulting in microvascular occlusion with hypoperfusion of the lungs. Lung immunothrombosis in type L ARDS results from neutrophil extracellular traps containing platelets and fibrin in the lung microvasculature, leading to hypoxemia due to impaired blood flow and a high ventilation/perfusion (VA/Q) ratio. COVID-19-associated ARDS is more vascular centric than the other types of ARDS. D-dimer levels have been monitored for the progression of microvascular thrombosis in COVID-19 patients. Early anticoagulation therapy in critical patients with high D-dimer levels may improve prognosis, including the prevention and/or alleviation of ARDS. CONCLUSIONS: Right-to-left shunts and high VA/Q ratios caused by lung microvascular thrombosis contribute to hypoxemia in type H and L ARDS, respectively. D-dimer monitoring-based anticoagulation therapy may prevent the progression to and/or worsening of ARDS in COVID-19 patients.


Тема - темы
COVID-19/physiopathology , Hemostasis/physiology , Hypoxia/physiopathology , Respiratory Distress Syndrome/physiopathology , Thrombosis/physiopathology , Anticoagulants/therapeutic use , Biomarkers/blood , Blood Platelets/metabolism , COVID-19/drug therapy , Extracellular Traps/metabolism , Fibrin/metabolism , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolysis , Humans , Lung/blood supply , Microvessels/physiopathology , Phenotype , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2 , Thrombosis/drug therapy
3.
Front Cell Infect Microbiol ; 12: 1000291, 2022.
Статья в английский | MEDLINE | ID: covidwho-2198709

Реферат

Zonulin has previously been related to intestinal permeability in various inflammatory diseases, and more recently to the physiopathology of severe COVID-19 infections. We analysed serum samples from a previous study of a Peruvian cohort of hospitalised COVID-19 patients, for the quantification of zonulin by sandwich ELISA. Comparisons with clinical data, haematological and biochemical parameters and cytokine/chemokine levels were made. We found higher baseline zonulin levels in deceased patients, and zonulin was associated with fatal outcome in multivariable analyses, even after adjustment for age, gender, and obesity. There were also positive correlations between zonulin, creatinine, D-dimer values and prothrombin time, while inverse correlations were found for Sa/FiO2 ratio and CCL5 (RANTES). Further longitudinal studies are recommended to analyse the variation of zonulin levels over time as well as their relationship with long-COVID.


Тема - темы
COVID-19 , Haptoglobins , Protein Precursors , Biomarkers , COVID-19/mortality , Chemokine CCL5 , Creatinine , Humans , Permeability , Peru/epidemiology
5.
Alzheimers Dement ; 18(11): 2167-2175, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2172368

Реферат

INTRODUCTION: Several investigations have argued for a strong relationship between neuroinflammation and amyloid metabolism but it is still unclear whether inflammation exerts a pro-amyloidogenic effect, amplifies the neurotoxic effect of amyloid, or is protective. METHODS: Forty-two patients with acute encephalitis (ENC) and 18 controls underwent an extended cerebrospinal fluid (CSF) panel of inflammatory, amyloid (Aß40, 42, and 38, sAPP-α, sAPP-ß), glial, and neuronal biomarkers. Linear and non-linear correlations between CSF biomarkers were evaluated studying conditional independence relationships. RESULTS: CSF levels of inflammatory cytokines and neuronal/glial markers were higher in ENC compared to controls, whereas the levels of amyloid-related markers did not differ. Inflammatory markers were not associated with amyloid markers but exhibited a correlation with glial and neuronal markers in conditional independence analysis. DISCUSSION: By an extensive CSF biomarkers analysis, this study showed that an acute neuroinflammation state, which is associated with glial activation and neuronal damage, does not influence amyloid homeostasis.


Тема - темы
Alzheimer Disease , Amyloidosis , Encephalitis , Humans , Amyloid beta-Peptides/metabolism , tau Proteins/cerebrospinal fluid , Alzheimer Disease/cerebrospinal fluid , Neuroinflammatory Diseases , Biomarkers/cerebrospinal fluid , Amyloidogenic Proteins , Peptide Fragments/cerebrospinal fluid
6.
Ann Allergy Asthma Immunol ; 129(1): 27-34, 2022 07.
Статья в английский | MEDLINE | ID: covidwho-2149293

Реферат

OBJECTIVE: To summarize the existing literature for several promising minimally invasive tests to measure disease activity in eosinophilic esophagitis (EoE). DATA SOURCES: Literature searches were performed using PubMed. Keyword combinations included eosinophilic esophagitis and minimally invasive techniques, including the esophageal string test, Cytosponge, transnasal endoscopy, technetium-labeled heparin, and noninvasive biomarkers. STUDY SELECTIONS: Retrospective and prospective observational studies, peer-reviewed reviews, and systematic reviews were selected. Data were reviewed and summarized. RESULTS: Various techniques have been developed in recent years to measure disease activity in EoE without the need for conventional endoscopy. Our review summarizes the data on these techniques, the benefits and limitations, and future directions for implementation in both research and clinical care. CONCLUSION: Tremendous progress has been made toward developing minimally invasive techniques to measure disease activity in EoE. Each of the techniques mentioned in this review has advantages and disadvantages, and some are closer to widespread use than others.


Тема - темы
Eosinophilic Esophagitis , Biomarkers , Eosinophilic Esophagitis/diagnosis , Humans , Observational Studies as Topic , Prospective Studies , Retrospective Studies
7.
Elife ; 92020 08 17.
Статья в английский | MEDLINE | ID: covidwho-2155739

Реферат

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.


Тема - темы
Betacoronavirus/isolation & purification , Blood Coagulation Disorders/diagnosis , Blood Coagulation Tests , Blood Coagulation , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Aged , Betacoronavirus/pathogenicity , Biomarkers/blood , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/virology , COVID-19 , COVID-19 Testing , Coronavirus Infections/blood , Coronavirus Infections/virology , Disease Progression , Female , Fibrinogen/metabolism , Host Microbial Interactions , Humans , Leukocyte Count , Longitudinal Studies , Male , Middle Aged , Pandemics , Platelet Count , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , SARS-CoV-2 , Time Factors
8.
Hypertension ; 76(5): 1526-1536, 2020 11.
Статья в английский | MEDLINE | ID: covidwho-2153220

Реферат

ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.


Тема - темы
Coronavirus Infections/epidemiology , Disease Outbreaks/statistics & numerical data , Disease Progression , Heart Failure/enzymology , Heart Failure/physiopathology , Peptidyl-Dipeptidase A/blood , Pneumonia, Viral/epidemiology , Academic Medical Centers , Analysis of Variance , Angiotensin-Converting Enzyme 2 , Biomarkers/metabolism , COVID-19 , Cohort Studies , Coronavirus Infections/prevention & control , Female , Humans , Linear Models , Male , Middle Aged , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Prognosis , Proportional Hazards Models , Proteomics/methods , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , United States
9.
Front Immunol ; 13: 1007102, 2022.
Статья в английский | MEDLINE | ID: covidwho-2163013

Реферат

Background: The complement system is an essential component of our innate defense and plays a vital role in the pathogenesis of many diseases. Assessment of complement activation is critical in monitoring both disease progression and response to therapy. Complement analysis requires accurate and standardized sampling and assay procedures, which has proven to be challenging. Objective: We performed a systematic analysis of the current methods used to assess complement components and reviewed whether the identified studies performed their complement measurements according to the recommended practice regarding pre-analytical sample handling and assay technique. Results are supplemented with own data regarding the assessment of key complement biomarkers to illustrate the importance of accurate sampling and measuring of complement components. Methods: A literature search using the Pubmed/MEDLINE database was performed focusing on studies measuring the key complement components C3, C5 and/or their split products and/or the soluble variant of the terminal C5b-9 complement complex (sTCC) in human blood samples that were published between February 2017 and February 2022. The identified studies were reviewed whether they had used the correct sample type and techniques for their analyses. Results: A total of 92 out of 376 studies were selected for full-text analysis. Forty-five studies (49%) were identified as using the correct sample type and techniques for their complement analyses, while 25 studies (27%) did not use the correct sample type or technique. For 22 studies (24%), it was not specified which sample type was used. Conclusion: A substantial part of the reviewed studies did not use the appropriate sample type for assessing complement activation or did not mention which sample type was used. This deviation from the standardized procedure can lead to misinterpretation of complement biomarker levels and hampers proper comparison of complement measurements between studies. Therefore, this study underlines the necessity of general guidelines for accurate and standardized complement analysis.


Тема - темы
Complement Activation , Complement C5 , Humans , Complement C3 , Complement Membrane Attack Complex , Biomarkers
10.
EBioMedicine ; 85: 104296, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2158739

Реферат

BACKGROUND: COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response. METHODS: We studied a total of 85 lungs (n = 31 COVID autopsy samples; n = 7 influenza A autopsy samples; n = 18 interstitial lung disease explants; n = 24 healthy controls) using the highest resolution Synchrotron radiation-based hierarchical phase-contrast tomography, scanning electron microscopy of microvascular corrosion casts, immunohistochemistry, matrix-assisted laser desorption ionization mass spectrometry imaging, and analysis of mRNA expression and biological pathways. Plasma samples from all disease groups were used for liquid biomarker determination using ELISA. The anatomic/molecular data were analyzed as a function of patients' hospitalization time. FINDINGS: The observed patchy/mosaic appearance of COVID-19 in conventional lung imaging resulted from microvascular occlusion and secondary lobular ischemia. The length of hospitalization was associated with increased intussusceptive angiogenesis. This was associated with enhanced angiogenic, and fibrotic gene expression demonstrated by molecular profiling and metabolomic analysis. Increased plasma fibrosis markers correlated with their pulmonary tissue transcript levels and predicted disease severity. Plasma analysis confirmed distinct fibrosis biomarkers (TSP2, GDF15, IGFBP7, Pro-C3) that predicted the fatal trajectory in COVID-19. INTERPRETATION: Pulmonary severe COVID-19 is a consequence of secondary lobular microischemia and fibrotic remodelling, resulting in a distinctive form of fibrotic interstitial lung disease that contributes to long-COVID. FUNDING: This project was made possible by a number of funders. The full list can be found within the Declaration of interests / Acknowledgements section at the end of the manuscript.


Тема - темы
COVID-19 , Lung Diseases, Interstitial , Humans , Lung/diagnostic imaging , Lung/pathology , Lung Diseases, Interstitial/pathology , Fibrosis , Biomarkers/analysis , Ischemia/pathology
11.
Biomolecules ; 12(10)2022 10 21.
Статья в английский | MEDLINE | ID: covidwho-2154887

Реферат

Cardiovascular diseases (CVD) represent the leading cause of death in the world despite innovations in therapies and advances in the general management of patients [...].


Тема - темы
Cardiology , Cardiovascular Diseases , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/genetics , Cardiovascular Diseases/therapy , Biomarkers
12.
Front Immunol ; 13: 941742, 2022.
Статья в английский | MEDLINE | ID: covidwho-2154719

Реферат

Background: Thromboinflammation may influence disease outcome in COVID-19. We aimed to evaluate complement and endothelial cell activation in patients with confirmed COVID-19 compared to controls with clinically suspected but excluded SARS-CoV-2 infection. Methods: In a prospective, observational, single-center study, patients presenting with clinically suspected COVID-19 were recruited in the emergency department. Blood samples on presentation were obtained for analysis of C5a, sC5b-9, E-selectin, Galectin-3, ICAM-1 and VCAM-1. Results: 153 cases and 166 controls (suffering mainly from non-SARS-CoV-2 respiratory viral infections, non-infectious inflammatory conditions and bacterial pneumonia) were included. Hospital admission occurred in 62% and 45% of cases and controls, respectively. C5a and VCAM-1 concentrations were significantly elevated and E-selectin concentrations decreased in COVID-19 out- and inpatients compared to the respective controls. However, relative differences in outpatients vs. inpatients in most biomarkers were comparable between cases and controls. Elevated concentrations of C5a, Galectin-3, ICAM-1 and VCAM-1 on presentation were associated with the composite outcome of ICU- admission or 30-day mortality in COVID-19 and controls, yet more pronounced in COVID-19. C5a and sC5b-9 concentrations were significantly higher in COVID-19 males vs. females, which was not observed in the control group. Conclusions: Our data indicate an activation of the complement cascade and endothelium in COVID-19 beyond a nonspecific inflammatory trigger as observed in controls (i.e., "over"-activation).


Тема - темы
COVID-19 , Thrombosis , Biomarkers , Complement System Proteins , E-Selectin , Endothelial Cells , Female , Galectin 3 , Humans , Inflammation , Intercellular Adhesion Molecule-1 , Male , Prospective Studies , SARS-CoV-2 , Vascular Cell Adhesion Molecule-1
13.
Front Cell Infect Microbiol ; 12: 922422, 2022.
Статья в английский | MEDLINE | ID: covidwho-2154675

Реферат

The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort. A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome). In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05). Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.


Тема - темы
COVID-19 , Biomarkers , COVID-19/complications , COVID-19/drug therapy , Cytokines , Humans , Interleukin-10 , Interleukin-17 , Interleukin-2 , Interleukin-4 , Interleukin-6 , Middle Aged , SARS-CoV-2 , Tumor Necrosis Factor-alpha
15.
Minerva Endocrinol (Torino) ; 47(3): 270-278, 2022 Sep.
Статья в английский | MEDLINE | ID: covidwho-2146119

Реферат

BACKGROUND: Despite severe acute respiratory syndrome (SARS)-Coronavirus (CoV-2) primarily targeting the lungs, the heart represents another critical virus target. Thus, the identification of SARS-CoV-2 disease of 2019 (COVID-19)-associated biomarkers would be beneficial to stratify prognosis and the risk of developing cardiac complications. Aldosterone and galectin-3 promote fibrosis and inflammation and are considered a prognostic biomarker of lung and adverse cardiac remodeling. Here, we tested whether galectin-3 and aldosterone levels can predict adverse cardiac outcomes in COVID-19 patients. METHODS: To this aim, we assessed galectin-3 and aldosterone serum levels in 51 patients diagnosed with COVID-19, using a population of 19 healthy subjects as controls. In in-vitro studies, we employed 3T3 fibroblasts to assess the potential roles of aldosterone and galectin-3 in fibroblast activation. RESULTS: Serum galectin-3 levels were more elevated in COVID-19 patients than healthy controls and correlated with COVID-19 severity classification and cardiac troponin-I (cTnI) serum levels. Furthermore, we observed an augmented secretion of aldosterone in COVID-19 patients. This adrenal hormone is a direct stimulator of galectin-3 secretion; therefore, we surmised that this axis could perpetrate fibrosis and adverse remodeling in these subjects. Thus, we stimulated fibroblasts with 10% of serum from COVID-19 patients. This challenge markedly rose the expression of smooth muscle alpha (α)-2 actin (ACTA2), a myofibroblast marker. CONCLUSIONS: Our study suggests that COVID-19 can affect cardiac structure and function by triggering aldosterone and galectin-3 release that may serve as prognostic and therapeutic biomarkers while monitoring the course of cardiac complications in patients suffering from COVID-19.


Тема - темы
COVID-19 , Galectin 3 , Actins , Aldosterone , Biomarkers , COVID-19/complications , Fibrosis , Humans , SARS-CoV-2 , Troponin I
16.
Ann Afr Med ; 21(4): 371-376, 2022.
Статья в английский | MEDLINE | ID: covidwho-2144095

Реферат

Introduction: COVID 19 pandemic has given rise to several challenges to clinicians and one of the keys in this is to predict the set of patients who progress from mild disease to moderate and severe. Apart from the symptomatology and signs, there are several lab parameters varying from biochemical, hematological to radiological parameters which help us in stratifying the stage of disease and also in deciding on which set of patients need close and vigilant monitoring. This would help us in better stratification of disease and utilize the available infrastructure and resources in an optimum way for better management of the disease. Aim: To analyze the early warning efficiency of laboratory parameters individually or in combination in predicting the progress of disease in patients from mild to moderate/severe disease. Materials and Methods: This was taken up as a retrospective study with 100 cases and 100 controls. The demographic details, inflammatory markers, biochemical markers and hematological markers were analyzed. Test of significance was employed to compare categorical variables while student t-test was employed to test the difference in the mean value such as age between case and control (Mann-Whitney U-test in parameters not having normal distribution). Receiver operating characteristic (ROC) curve was constructed for these parameters using cases and controls and area under the curve (AUC) were estimated which was used as an indicator of sensitivity and specificity of the parameter in their early warning efficiency. The critical values for each of the parameters either individually or in combination was estimated as well. Results: Among the parameters C reactive protein (CRP), d-dimers and eosinopenia have the best early warning efficiency. The area under the ROCs curve for neutrophil lymphocyte ratio (NLR), CRP. Ferritin, lactate dehydrogenase, Eosinopenia was 0.609, 0.947, 0.614, 0.554, 0.617 respectively at triage. However, a combination of eosinopenia with CRP (AUC-0.732) or NLR with CRP (AUC-0.728) have a good sensitivity and specificity in predicting the outcome regarding the progression of the disease. Conclusions: Among the parameters, CRP, d-dimers, Eosinopenia and NLR have the best early warning efficiency. However, a combination of Eosinopenia and CRP at triage should also serve as a red flag sign in patients apart from the well-known NLR and IL6 values.


Résumé Introduction: La pandémie covide 19 a relevé plusieurs défis aux cliniciens et l'une des clés dans ce domaine est de prédire l'ensemble des patients qui passent d'une maladie légère à modérée et sévère. Outre la symptomatologie et les signes, plusieurs paramètres de laboratoire variant des paramètres biochimiques, hématologiques à radiologiques qui nous aident à stratifier le stade de la maladie et également à décider quel ensemble de patients nécessite une surveillance étroite et vigilante. Cela nous aiderait à mieux stratification des maladies et à utiliser l'infrastructure et les ressources disponibles de manière optimale pour une meilleure prise en charge de la maladie. Objectif: Analyser l'efficacité d'alerte précoce des paramètres de laboratoire individuellement ou en combinaison pour prédire les progrès des maladies chez les patients d'une maladie légère à modérée / sévère. Matériaux et méthodes: Ceci a été considéré comme une étude rétrospective avec 100 cas et 100 contrôles. Les détails démographiques, les marqueurs inflammatoires, les marqueurs biochimiques et les marqueurs hématologiques ont été analysés. Le test de signification a été utilisé pour comparer les variables catégorielles tandis que le test T des étudiants a été utilisé pour tester la différence de valeur moyenne telle que l'âge entre le cas et le contrôle (test U Mann - Whitney dans les paramètres n'ayant pas de distribution normale). La courbe des caractéristiques de fonctionnement du récepteur (ROC) a été construite pour ces paramètres en utilisant les cas et les contrôles et la zone sous la courbe (AUC) ont été estimés qui ont été utilisés comme indicateur de sensibilité et de spécificité du paramètre dans leur efficacité d'alerte précoce. Les valeurs critiques pour chacun des paramètres individuellement ou en combinaison ont également été estimées. Résultats: Parmi les paramètres C Protein réactif (CRP), les D - dimères et l'éosinopénie ont la meilleure efficacité d'alerte précoce. La zone sous la courbe ROCS pour le rapport lymphocyte des neutrophiles (NLR), CRP. La ferritine, la lactate déshydrogénase, l'éosinopénie était de 0,609, 0,947, 0,614, 0,554, 0,617 respectivement au triage. Cependant, une combinaison d'éosinopénie avec CRP (AUC - 0,732) ou NLR avec CRP (AUC - 0,728) a une bonne sensibilité et spécificité pour prédire le résultat concernant la progression de la maladie. Conclusions: Parmi les paramètres, le CRP, les D - dimères, l'éosinopénie et le NLR ont la meilleure efficacité d'alerte précoce. Cependant, une combinaison d'éosinopénie et de CRP au triage devrait également servir de signe du drapeau rouge chez les patients en dehors des valeurs NLR et IL6 bien connues. Mots-clés: C Protéine réactive, efficacité d'alerte précoce, éosinopénie, progression de la maladie dans Covid ­ 19.


Тема - темы
COVID-19 , Humans , Retrospective Studies , Lymphocytes , Neutrophils , Biomarkers
17.
Int J Mol Sci ; 23(22)2022 Nov 08.
Статья в английский | MEDLINE | ID: covidwho-2143213

Реферат

Tuberculosis (TB) is a transmissible disease listed as one of the 10 leading causes of death worldwide (10 million infected in 2019). A swift and precise diagnosis is essential to forestall its transmission, for which the discovery of effective diagnostic biomarkers is crucial. In this study, we aimed to discover molecular biomarkers for the early diagnosis of tuberculosis. Two independent cohorts comprising 29 and 34 subjects were assayed by proteomics, and 49 were included for metabolomic analysis. All subjects were arranged into three experimental groups-healthy controls (controls), latent TB infection (LTBI), and TB patients. LC-MS/MS blood serum protein and metabolite levels were submitted to univariate, multivariate, and ROC analysis. From the 149 proteins quantified in the discovery set, 25 were found to be differentially abundant between controls and TB patients. The AUC, specificity, and sensitivity, determined by ROC statistical analysis of the model composed of four of these proteins considering both proteomic sets, were 0.96, 93%, and 91%, respectively. The five metabolites (9-methyluric acid, indole-3-lactic acid, trans-3-indoleacrylic acid, hexanoylglycine, and N-acetyl-L-leucine) that better discriminate the control and TB patient groups (VIP > 1.75) from a total of 92 metabolites quantified in both ionization modes were submitted to ROC analysis. An AUC = 1 was determined, with all samples being correctly assigned to the respective experimental group. An integrated ROC analysis enrolling one protein and four metabolites was also performed for the common control and TB patients in the proteomic and metabolomic groups. This combined signature correctly assigned the 12 controls and 12 patients used only for prediction (AUC = 1, specificity = 100%, and sensitivity = 100%). This multiomics approach revealed a biomarker signature for tuberculosis diagnosis that could be potentially used for developing a point-of-care diagnosis clinical test.


Тема - темы
Latent Tuberculosis , Tuberculosis , Humans , Proteomics , Chromatography, Liquid , Tandem Mass Spectrometry , Tuberculosis/diagnosis , Latent Tuberculosis/diagnosis , Biomarkers
18.
Front Immunol ; 13: 1027122, 2022.
Статья в английский | MEDLINE | ID: covidwho-2142033

Реферат

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the highly infectious Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). There is an urgent need for biomarkers that will help in better stratification of patients and contribute to personalized treatments. We performed targeted proteomics using the Olink platform and systematically investigated protein concentrations in 350 hospitalized COVID-19 patients, 186 post-COVID-19 individuals, and 61 healthy individuals from 3 independent cohorts. Results revealed a signature of acute SARS-CoV-2 infection, which is represented by inflammatory biomarkers, chemokines and complement-related factors. Furthermore, the circulating proteome is still significantly affected in post-COVID-19 samples several weeks after infection. Post-COVID-19 individuals are characterized by upregulation of mediators of the tumor necrosis (TNF)-α signaling pathways and proteins related to transforming growth factor (TGF)-ß. In addition, the circulating proteome is able to differentiate between patients with different COVID-19 disease severities, and is associated with the time after infection. These results provide important insights into changes induced by SARS-CoV-2 infection at the proteomic level by integrating several cohorts to obtain a large disease spectrum, including variation in disease severity and time after infection. These findings could guide the development of host-directed therapy in COVID-19.


Тема - темы
COVID-19 , Proteomics , Humans , Proteome , SARS-CoV-2 , Biomarkers
19.
Front Immunol ; 13: 975848, 2022.
Статья в английский | MEDLINE | ID: covidwho-2142004

Реферат

Corona Virus Disease 2019 (COVID-19), an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread rapidly worldwide, resulting in a pandemic with a high mortality rate. In clinical practice, we have noted that many critically ill or critically ill patients with COVID-19 present with typical sepsis-related clinical manifestations, including multiple organ dysfunction syndrome, coagulopathy, and septic shock. In addition, it has been demonstrated that severe COVID-19 has some pathological similarities with sepsis, such as cytokine storm, hypercoagulable state after blood balance is disrupted and neutrophil dysfunction. Considering the parallels between COVID-19 and non-SARS-CoV-2 induced sepsis (hereafter referred to as sepsis), the aim of this study was to analyze the underlying molecular mechanisms between these two diseases by bioinformatics and a systems biology approach, providing new insights into the pathogenesis of COVID-19 and the development of new treatments. Specifically, the gene expression profiles of COVID-19 and sepsis patients were obtained from the Gene Expression Omnibus (GEO) database and compared to extract common differentially expressed genes (DEGs). Subsequently, common DEGs were used to investigate the genetic links between COVID-19 and sepsis. Based on enrichment analysis of common DEGs, many pathways closely related to inflammatory response were observed, such as Cytokine-cytokine receptor interaction pathway and NF-kappa B signaling pathway. In addition, protein-protein interaction networks and gene regulatory networks of common DEGs were constructed, and the analysis results showed that ITGAM may be a potential key biomarker base on regulatory analysis. Furthermore, a disease diagnostic model and risk prediction nomogram for COVID-19 were constructed using machine learning methods. Finally, potential therapeutic agents, including progesterone and emetine, were screened through drug-protein interaction networks and molecular docking simulations. We hope to provide new strategies for future research and treatment related to COVID-19 by elucidating the pathogenesis and genetic mechanisms between COVID-19 and sepsis.


Тема - темы
COVID-19 , Sepsis , Biomarkers , Computational Biology/methods , Critical Illness , Cytokines/genetics , Emetine , Gene Expression Profiling/methods , Humans , Molecular Docking Simulation , NF-kappa B/genetics , Progesterone , Receptors, Cytokine/genetics , SARS-CoV-2 , Sepsis/genetics , Sepsis/metabolism
20.
PLoS One ; 17(11): e0278145, 2022.
Статья в английский | MEDLINE | ID: covidwho-2140687

Реферат

Coronavirus disease 2019 (COVID-19), a highly contagious pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly and remains a challenge to global public health. COVID-19 patients manifest various symptoms from mild to severe cases with poor clinical outcomes. Prognostic values of novel markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and C-reactive protein to lymphocyte ratio (CLR) calculated from routine laboratory parameters have recently been reported to predict severe cases; however, whether this investigation can guide oxygen therapy in COVID-19 patients remains unclear. In this study, we assessed the ability of these markers in screening and predicting types of oxygen therapy in COVID-19 patients. The retrospective data of 474 COVID-19 patients were categorized into mild and severe cases and grouped according to the types of oxygen therapy requirement, including noninvasive oxygen support, high-flow nasal cannula and invasive mechanical ventilator. Among the novel markers, the ROC curve analysis indicated a screening cutoff of CRP ≥ 30.0 mg/L, NLR ≥ 3.0 and CLR ≥ 25 in predicting the requirement of any type of oxygen support. The NLR and CLR with increasing cut-off values have discriminative power with high accuracy and specificity for more effective oxygen therapy with a high-flow nasal cannula (NLR ≥ 6.0 and CLR ≥ 60) and mechanical ventilator (NLR ≥ 8.0 and CLR ≥ 80). Our study thus identifies potential markers to differentiate the suitable management of oxygen therapy in COVID-19 patients at an earlier time for improving disease outcomes with limited respiratory support resources.


Тема - темы
COVID-19 , Humans , COVID-19/therapy , SARS-CoV-2 , Oxygen , Retrospective Studies , Oxygen Inhalation Therapy , Biomarkers , C-Reactive Protein
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