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2.
Sci Rep ; 10(1): 15058, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929124

RESUMO

Coronavirus disease 2019 (COVID-19) is an important and urgent threat to global health. Inflammation factors are important for COVID-19 mortality, and we aim to explore whether the baseline levels of procalcitonin (PCT), C-reaction protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) are associated with an increased risk of mortality in patients with COVID-19. A retrospective study was conducted and a total of 76 patients with confirmed COVID-19 were included between January 17, 2020 to March 2, 2020, of these cases, 17 patients were dead. After adjusting covariates, PCT (≥ 0.10 ng/mL) and CRP (≥ 52.14 mg/L) exhibited independent increasing risks of mortality were used hazard ratio (HR) of 52.68 (95% confidence interval [CI]: 1.77-1571.66) and 5.47 (95% CI: 1.04-28.72), respectively. However, NRL (≥ 3.59) was not found to be an independent risk factor for death in our study. Furthermore, the elevated PCT levels were still associated with increasing risk of mortality in the old age group (age ≥ 60 y), and in the critically severe and severe patients after adjustment for complications. Thu Baseline levels of PCT and CRP have been addressed as independent predictors of mortality in patients with COVID-19.


Assuntos
Proteína C-Reativa/análise , Infecções por Coronavirus/diagnóstico , Linfócitos/citologia , Neutrófilos/citologia , Pneumonia Viral/diagnóstico , Pró-Calcitonina/análise , Adolescente , Adulto , Idoso , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , China , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
3.
Eur J Med Res ; 25(1): 30, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746929

RESUMO

BACKGROUND: More severe cases of COVID- 19 are more likely to be hospitalized and around one-fifth, needing ICU admission. Understanding the common laboratory features of COVID-19 in more severe cases versus non-severe patients could be quite useful for clinicians and might help to predict the model of disease progression. This systematic review and meta-analysis aimed to compare the laboratory test findings in severe vs. non-severe confirmed infected cases of COVID-19. METHODS: Electronic databases were systematically searched in PubMed, EMBASE, Scopus, Web of Science, and Google Scholar from the beginning of 2019 to 3rd of March 2020. Heterogeneity across included studies was determined using Cochrane's Q test and the I2 statistic. We used the fixed or random-effect models to pool the weighted mean differences (WMDs) or standardized mean differences and 95% confidence intervals (CIs). FINDINGS: Out of a total of 3009 citations, 17 articles (22 studies, 21 from China and one study from Singapore) with 3396 ranging from 12 to1099 patients were included. Our meta-analyses showed a significant decrease in lymphocyte, monocyte, and eosinophil, hemoglobin, platelet, albumin, serum sodium, lymphocyte to C-reactive protein ratio (LCR), leukocyte to C-reactive protein ratio (LeCR), leukocyte to IL-6 ratio (LeIR), and an increase in the neutrophil, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, blood urea nitrogen (BUN), creatinine (Cr), erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Procalcitonin (PCT), lactate dehydrogenase (LDH), fibrinogen, prothrombin time (PT), D-dimer, glucose level, and neutrophil to lymphocyte ratio (NLR) in the severe group compared with the non-severe group. No significant changes in white blood cells (WBC), Creatine Kinase (CK), troponin I, myoglobin, IL-6 and K between the two groups were observed. INTERPRETATION: This meta-analysis provides evidence for the differentiation of severe cases of COVID-19 based on laboratory test results at the time of ICU admission. Future well-methodologically designed studies from other populations are strongly recommended.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Ásia , Grupo com Ancestrais do Continente Asiático , Betacoronavirus , Coagulação Sanguínea , Glicemia/análise , Sedimentação Sanguínea , Proteína C-Reativa/análise , China , Técnicas de Laboratório Clínico , Infecções por Coronavirus/epidemiologia , Progressão da Doença , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hospitalização , Humanos , Inflamação , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Linfócitos/citologia , Neutrófilos/citologia , Pandemias , Pneumonia Viral/epidemiologia , Singapura , Resultado do Tratamento , Troponina I/sangue
4.
Zhonghua Xin Xue Guan Bing Za Zhi ; 48(7): 572-579, 2020 Jul 24.
Artigo em Chinês | MEDLINE | ID: mdl-32842269

RESUMO

Objective: To explore the predictive value of neutrophil/lymphocyte ratio (NLR) on myocardial injury in severe COVID-19 patients. Methods: In this single-center retrospective cohort study, we collected and analyzed data form 133 severe COVID-19 patients admitted to Renmin Hospital of Wuhan University (Eastern District) from January 30 to February 18, 2020. Patients were divided into myocardial injury group (n=29) and non-myocardial injury group (n=104) according the presence or absence of myocardial injury. The general information of patients was collected by electronic medical record database system. All patients were followed up for 30 days, the organ injury and/or dysfunction were monitored, the in-hospital death was compared between the two groups, and the disease progression was reevaluated and classified at 14 days after initial hospitalization. Logistic regression analysis was performed to identify risk factors of myocardial injury in severe COVID-19 patients. The ROC of NLR was calculated, and the AUC was determined to estimate the optimal cut-off value of NLR for predicting myocardial injury in severe cases of COVID-19. Results: There was statistical significance in age, respiratory frequency, systolic blood pressure, symptoms of dyspnea, previous chronic obstructive pulmonary disease, coronary heart disease history, white blood cells, neutrophils, lymphocytes, platelets, C-reactive protein, platelet counting, aspartate transaminase, albumin, total bilirubin, direct bilirubin, urea, estimated glomerular filtration rate, total cholesterol, low-density lipoprotein cholesterol, D-dimer, CD3+, CD4+, partial pressure of oxygen, partial pressure of CO2, blood oxygen saturation, other organ injury, clinical outcome and prognosis between patients with myocardial injury and without myocardial injury (all P<0.05). Multivariate logistic regression analysis showed that NLR was a risk factor for myocardial injury (OR=1.066,95%CI 1.021-1.111,P=0.033). ROC curve showed that NLR predicting AUC of myocardial injury in severe COVID-19 patients was 0.774 (95%CI 0.694-0.842), the optimal cut-off value of NLR was 5.768, with a sensitivity of 82.8%, and specificity of 69.5%. Conclusion: NLR may be used to predict myocardial injury in severe COVID-19 patients.


Assuntos
Infecções por Coronavirus/patologia , Cardiopatias/virologia , Linfócitos/citologia , Miocárdio/patologia , Neutrófilos/citologia , Pneumonia Viral/patologia , Betacoronavirus , Humanos , Pandemias , Prognóstico , Curva ROC , Estudos Retrospectivos
5.
Medicine (Baltimore) ; 99(34): e21876, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846844

RESUMO

BACKGROUND: Cancer continues to be a severe global health problem and the leading cause of death worldwide. Chemotherapy as the main treatment has various side effects, of which marrow suppression is the most common one. Acupuncture had shown clinical effects for marrow suppression after chemotherapy in many studies. However, the efficacy and safety of acupuncture therapy for marrow suppression after chemotherapy remains unclear. OBJECTIVE: This protocol aims to evaluate the efficacy and safety of acupuncture for marrow suppression after chemotherapy according to the existing randomized controlled trials. METHODS AND ANALYSIS: The randomized controlled trials on acupuncture therapy for marrow suppression after chemotherapy will be searched in the database of Embase, PubMed and Cochrane Library, Allied and Complementary Medicine Database (AMED), Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), and related registration platforms (WHO ICTRP, Clinical Trials, and Chinese Clinical Trial Register [ChiCTR]), Grey Literature Database from inception to 1 August 2020. The primary outcomes will be assessed using white blood cell (WBC) count, platelet count, hemoglobin count and the number of neutrophils (N). Review Manager V.5.3 software will be applied for statistical analyses. We will measure the risk of bias of the included studies with Cochrane Collaboration Risk of Bias Tool. Finally, Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) will be used to grade the overall quality of evidence. And we will use the intra-group correlation coefficient to assess the consistency of reviewers. RESULT: This systematic review and meta-analysis will put a high-quality synthesis of the efficacy and safety of acupuncture treatment in marrow suppression after chemotherapy. CONCLUSION: The conclusion of this systematic review will provide evidence to assess acupuncture therapy is an efficacy and safe intervention to treat and control marrow suppression after chemotherapy. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020163336.


Assuntos
Terapia por Acupuntura/métodos , Antineoplásicos/efeitos adversos , Células da Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Tratamento Farmacológico/métodos , Feminino , Hemoglobinas/análise , Humanos , Contagem de Leucócitos/métodos , Masculino , Neoplasias/tratamento farmacológico , Neutrófilos/citologia , Contagem de Plaquetas/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
6.
Nat Commun ; 11(1): 4027, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788676

RESUMO

Programmed cell death or apoptosis is a central biological process that is dysregulated in many diseases, including inflammatory conditions and cancer. The detection and quantification of apoptotic cells in vivo is hampered by the need for fixatives or washing steps for non-fluorogenic reagents, and by the low levels of free calcium in diseased tissues that restrict the use of annexins. In this manuscript, we report the rational design of a highly stable fluorogenic peptide (termed Apo-15) that selectively stains apoptotic cells in vitro and in vivo in a calcium-independent manner and under wash-free conditions. Furthermore, using a combination of chemical and biophysical methods, we identify phosphatidylserine as a molecular target of Apo-15. We demonstrate that Apo-15 can be used for the quantification and imaging of drug-induced apoptosis in preclinical mouse models, thus creating opportunities for assessing the in vivo efficacy of anti-inflammatory and anti-cancer therapeutics.


Assuntos
Apoptose , Imageamento Tridimensional , Peptídeos Cíclicos/farmacologia , Sequência de Aminoácidos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Feminino , Humanos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/química , Fagocitose/efeitos dos fármacos , Fosfatidilserinas/metabolismo
7.
Pediatrics ; 146(3)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32843440

RESUMO

BACKGROUND: New biomarkers like procalcitonin and C-reactive protein may help design an accurate decision support tool used to identify children with pleocytosis at low or high risk of bacterial meningitis. Our objective was to develop and validate a score (that we call the meningitis score for emergencies [MSE]) to distinguish bacterial meningitis from aseptic meningitis in children with pleocytosis when initially evaluated at the emergency department. METHODS: We included children between 29 days and 14 years old with meningitis admitted to 25 Spanish emergency departments. A retrospective cohort from between 2011 and 2016 was used as the derivation set and a prospective cohort recruited during 2017 and 2018 was used as the validation set. RESULTS: Among the 1009 patients included, there were 917 cases of aseptic meningitis and 92 of bacterial meningitis. Using multivariable logistic regression analysis, we identified the following predictors of bacterial meningitis from the derivation set: procalcitonin >1.2 ng/mL, cerebrospinal fluid (CSF) protein >80 mg/dL, CSF absolute neutrophil count >1000 cells per mm3, and C-reactive protein >40 mg/L. Using the derivation set, we developed the MSE, assigning 3 points for procalcitonin, 2 points for CSF protein, and 1 point for each of the other variables. An MSE ≥1 predicted bacterial meningitis with a sensitivity of 100% (95% confidence interval [CI]: 95.0%-100%), a specificity of 83.2 (95% CI: 80.6-85.5), and a negative predictive value of 100% (95% CI 99.4-100.) CONCLUSIONS: The MSE accurately distinguishes bacterial from aseptic meningitis in children with CSF pleocytosis.


Assuntos
Regras de Decisão Clínica , Meningite Asséptica/diagnóstico , Meningites Bacterianas/diagnóstico , Adolescente , Biomarcadores/sangue , Proteína C-Reativa/análise , Proteínas do Líquido Cefalorraquidiano/análise , Criança , Pré-Escolar , Intervalos de Confiança , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Contagem de Leucócitos , Leucocitose/diagnóstico , Modelos Logísticos , Masculino , Meningite Asséptica/sangue , Meningite Asséptica/epidemiologia , Meningites Bacterianas/sangue , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Neutrófilos/citologia , Pró-Calcitonina/sangue , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Tamanho da Amostra , Sensibilidade e Especificidade , Espanha
8.
Circulation ; 142(12): 1176-1189, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32755393

RESUMO

BACKGROUND: Severe acute respiratory syndrome corona virus 2 infection causes severe pneumonia (coronavirus disease 2019 [COVID-19]), but the mechanisms of subsequent respiratory failure and complicating renal and myocardial involvement are poorly understood. In addition, a systemic prothrombotic phenotype has been reported in patients with COVID-19. METHODS: A total of 62 subjects were included in our study (n=38 patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19 and n=24 non-COVID-19 controls). We performed histopathologic assessment of autopsy cases, surface marker-based phenotyping of neutrophils and platelets, and functional assays for platelet, neutrophil functions, and coagulation tests, as well. RESULTS: We provide evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis. We show that, in COVID-19, inflammatory microvascular thrombi are present in the lung, kidney, and heart, containing neutrophil extracellular traps associated with platelets and fibrin. Patients with COVID-19 also present with neutrophil-platelet aggregates and a distinct neutrophil and platelet activation pattern in blood, which changes with disease severity. Whereas cases of intermediate severity show an exhausted platelet and hyporeactive neutrophil phenotype, patients severely affected with COVID-19 are characterized by excessive platelet and neutrophil activation in comparison with healthy controls and non-COVID-19 pneumonia. Dysregulated immunothrombosis in severe acute respiratory syndrome corona virus 2 pneumonia is linked to both acute respiratory distress syndrome and systemic hypercoagulability. CONCLUSIONS: Taken together, our data point to immunothrombotic dysregulation as a key marker of disease severity in COVID-19. Further work is necessary to determine the role of immunothrombosis in COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Insuficiência Respiratória/etiologia , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Plaquetas/citologia , Plaquetas/metabolismo , Plaquetas/patologia , Estudos de Casos e Controles , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Armadilhas Extracelulares/metabolismo , Humanos , Rim/patologia , Pulmão/patologia , Neutrófilos/citologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Pandemias , Fenótipo , Ativação Plaquetária , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Insuficiência Respiratória/diagnóstico , Índice de Gravidade de Doença , Trombose/complicações , Trombose/diagnóstico
9.
PLoS Pathog ; 16(8): e1008741, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32750085

RESUMO

Aspergillus fumigatus is an opportunistic mold that infects patients who are immunocompromised or have chronic lung disease, causing significant morbidity and mortality in these populations. While the factors governing the host response to A. fumigatus remain poorly defined, neutrophil recruitment to the site of infection is critical to clear the fungus. Galectin-3 is a mammalian ß-galactose-binding lectin with both antimicrobial and immunomodulatory activities, however the role of galectin-3 in the defense against molds has not been studied. Here we show that galectin-3 expression is markedly up-regulated in mice and humans with pulmonary aspergillosis. Galectin-3 deficient mice displayed increased fungal burden and higher mortality during pulmonary infection. In contrast to previous reports with pathogenic yeast, galectin-3 exhibited no antifungal activity against A. fumigatus in vitro. Galectin-3 deficient mice exhibited fewer neutrophils in their airways during infection, despite normal numbers of total lung neutrophils. Intravital imaging studies confirmed that galectin-3 was required for normal neutrophil migration to the airspaces during fungal infection. Adoptive transfer experiments demonstrated that stromal rather than neutrophil-intrinsic galectin-3 was necessary for normal neutrophil entry into the airspaces. Live cell imaging studies revealed that extracellular galectin-3 directly increases neutrophil motility. Taken together, these data demonstrate that extracellular galectin-3 facilitates recruitment of neutrophils to the site of A. fumigatus infection, and reveals a novel role for galectin-3 in host defense against fungal infections.


Assuntos
Aspergilose/imunologia , Aspergillus fumigatus/fisiologia , Galectina 3/imunologia , Pulmão/microbiologia , Neutrófilos/citologia , Animais , Aspergilose/genética , Aspergilose/microbiologia , Aspergilose/fisiopatologia , Aspergillus fumigatus/genética , Movimento Celular , Feminino , Galectina 3/genética , Humanos , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia
10.
Front Immunol ; 11: 1636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670298

RESUMO

The current pandemic of coronavirus disease 19 (COVID-19) has affected millions of individuals and caused thousands of deaths worldwide. The pathophysiology of the disease is complex and mostly unknown. Therefore, identifying the molecular mechanisms that promote progression of the disease is critical to overcome this pandemic. To address such issues, recent studies have reported transcriptomic profiles of cells, tissues and fluids from COVID-19 patients that mainly demonstrated activation of humoral immunity, dysregulated type I and III interferon expression, intense innate immune responses and inflammatory signaling. Here, we provide novel perspectives on the pathophysiology of COVID-19 using robust functional approaches to analyze public transcriptome datasets. In addition, we compared the transcriptional signature of COVID-19 patients with individuals infected with SARS-CoV-1 and Influenza A (IAV) viruses. We identified a core transcriptional signature induced by the respiratory viruses in peripheral leukocytes, whereas the absence of significant type I interferon/antiviral responses characterized SARS-CoV-2 infection. We also identified the higher expression of genes involved in metabolic pathways including heme biosynthesis, oxidative phosphorylation and tryptophan metabolism. A BTM-driven meta-analysis of bronchoalveolar lavage fluid (BALF) from COVID-19 patients showed significant enrichment for neutrophils and chemokines, which were also significant in data from lung tissue of one deceased COVID-19 patient. Importantly, our results indicate higher expression of genes related to oxidative phosphorylation both in peripheral mononuclear leukocytes and BALF, suggesting a critical role for mitochondrial activity during SARS-CoV-2 infection. Collectively, these data point for immunopathological features and targets that can be therapeutically exploited to control COVID-19.


Assuntos
Betacoronavirus/imunologia , Quimiocinas/sangue , Infecções por Coronavirus/imunologia , Interferon Tipo I/sangue , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Infecções por Coronavirus/patologia , Perfilação da Expressão Gênica , Humanos , Inflamação/virologia , Influenza Humana/imunologia , Interferon Tipo I/imunologia , Neutrófilos/citologia , Fosforilação Oxidativa , Pandemias , Pneumonia Viral/patologia , Transcriptoma/genética
11.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(7): 965-971, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32701240

RESUMO

OBJECTIVE: To identify the key biochemical indicators that affect the clinical type and outcomes of COVID-19 patients and explore the application of neutrophil/lymphocyte ratio (NLR) in COVID-19. METHODS: Ninety-three patients with confirmed diagnosis of COVID-19 admitted in Ezhou Central Hospital from February to April in 2020 were analyzed. Among them, 43 patients were selected from Intensive Care Unit (ICU) with the diagnosis of critical type of COVID-19, and 50 cases of common type were selected from the Department of Respiratory Medicine. The baseline data, blood routine test and biochemical indexes of the patients were collected on the first day of admission. NLRs of the patients were calculated, and COX survival analysis according to the NLR 4-category method was performed. The patients' outcomes were analyzed with receiver operating curves (ROCs). The patients were divided into two groups according to NLR cutoff value for comparison of the biochemical indexes. Based on the patients' outcomes, NLR cutoff value classification and clinical classification, multiple binary logistics regression was performed to screen the key variables and explore their significance in COVID-19. RESULTS: The NLR four-category method was not applicable for prognostic evaluation of the patients. The cut-off value of NLR for predict the prognosis of COVID-19 was 11.26, with a sensitivity of 0.903 and a specificity of 0.839; the laboratory indicators of the patients with NLR < 11.26 were similar to those in patients of the common type; the indicators were also similar between patients with NLR≥11.26 and those with critical type COVID-19. NLR, WBC, NEUT, PCT, DD, BUN, TNI, BNP, and LDH had significant effects on the clinical classification and outcome of the patients (P < 0.05); Cr, Ca, PH, and Lac had greater impact on the outcome of the patients (P < 0.05), while Na, PCO2 had greater impact on the clinical classification of the patients (P < 0.05). CONCLUSIONS: NLR can be used as an important reference for clinical classification, prognostic assessment, and biochemical abnormalities of COVID-19. Patients of critical type more frequently have bacterial infection with more serious inflammatory reactions, severer heart, lung and kidney damages, and much higher levels of DD and LDH than those of the common type. NLR, NEUT, DD, TNI, BNP, LDH, Ca, PCT, PH, and Lac have obvious influence on the prognosis of COVID-19 and should be observed dynamically.


Assuntos
Contagem de Células Sanguíneas , Infecções por Coronavirus , Linfócitos , Neutrófilos , Pandemias , Pneumonia Viral , Betacoronavirus , Contagem de Células Sanguíneas/normas , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Humanos , Linfócitos/citologia , Neutrófilos/citologia , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença
12.
Medicina (B Aires) ; 80 Suppl 3: 31-36, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32658845

RESUMO

In December 2019, a new coronavirus was identified as the cause of an outbreak of pneumonia and respiratory distress in Wuhan, China. It was declared pandemic in March 2020. It is important to know predictors of poor outcomes in order to optimize the strategies of care in newly diagnosed patients. The neutrophil to lymphocyte ratio (NLR) constitutes a novel prognostic marker for oncologic, cardiovascular and infectious diseases. We aimed to assess its prognostic value in COVID-19. We evaluated a retrospective cohort of 131 patients with COVID-19 from March to May 2020. We analyzed the association of an NLR = 3 with severe COVID-19, baseline characteristics of the population and the mortality rate. The median age was 52 years, and 54% were men. 21 patients presented criteria of severe disease, 9 of them required mechanical ventilation. NLR = 3 was found in 81% (18/21) of severe patients and in 33% (36/110) of mild patients (OR = 8.74. 95% CI 2.74-27.86; p < 0.001). Age and hypertension were associated with severe disease. A mortality rate of 7% (9) was obtained. Seven of the 9 patients who died presented NLR = 3, with a significant association between mortality and NLR = 3 (p = 0.03). NLR could be used in conjunction with other predictors, as an early prognostic marker in COVID-19 given its accessibility and low cost.


Assuntos
Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Linfócitos/fisiologia , Neutrófilos/fisiologia , Pandemias , Pneumonia Viral/diagnóstico , Fatores Etários , Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
13.
Artigo em Inglês | MEDLINE | ID: mdl-32612961

RESUMO

Background: Corona virus disease (COVID-19) is an infectious respiratory disease that has spread rapidly across the world. Many studies have already evaluated the clinical features of COVID-19, but how it compares with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) is still unclear. Moreover, COVID-19 mortality is correlated with disease severity, but indicators for severity grading have not been specified. We aimed to analyze the clinical characteristics of COVID-19 in comparison with SN-CAP and find indicators for disease severity in COVID-19. Methods: Patients diagnosed with COVID-19 and SN-CAP were enrolled. Clinical, radiological, and laboratory data were analyzed. Results: The numbers of COVID-19 and SN-CAP patients enrolled were 304 and 138, respectively. The age of the patients was not significantly different between the groups. Compared with SN-CAP, COVID-19 patients had more symptoms of fever and dyspnea; and showed significant difference in blood count results. Computed tomography (CT) imaging of COVID-19 patients showed patchy ground-glass opacities that correlated with disease severity, whereas the CT imaging of SN-CAP patients showed patchy high-density shadows. COVID-19 patients were classified into moderate, severe, and critically severe groups. The severe and critically severe groups had elevated levels of white blood cells (WBC), neutrophils, platelets, C-reaction protein (CRP), lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), troponin-I, creatinine, and blood urea nitrogen (BUN). However, they had decreased levels of lymphocytes, lymphocyte ratio, and albumin. Compared with the younger patients, the older COVID-19 individuals had more chronic diseases and significantly elevated levels of WBC, neutrophil, and CRP levels. Conclusion: SN-CAP showed more inflammatory reaction than COVID-19. Old people with chronic diseases are more susceptible to COVID-19 and have a high likelihood of developing severe and critically severe infection. Levels of WBC, lymphocytes, neutrophils, CRP, NLR, PLR, troponin-I, creatinine, and BUN are important indicators for severity grading in COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/patologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Adolescente , Adulto , Fatores Etários , Betacoronavirus , Análise Química do Sangue , Proteína C-Reativa/análise , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/patologia , Comorbidade , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Inflamação/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Pandemias , Contagem de Plaquetas , Pneumonia Bacteriana/mortalidade , Pneumonia Viral/mortalidade , Estudos Retrospectivos , Adulto Jovem
14.
EBioMedicine ; 57: 102880, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32645614

RESUMO

BACKGROUND: Information regarding risk factors associated with severe coronavirus disease (COVID-19) is limited. This study aimed to develop a model for predicting COVID-19 severity. METHODS: Overall, 690 patients with confirmed COVID-19 were recruited between 1 January and 18 March 2020 from hospitals in Honghu and Nanchang; finally, 442 patients were assessed. Data were categorised into the training and test sets to develop and validate the model, respectively. FINDINGS: A predictive HNC-LL (Hypertension, Neutrophil count, C-reactive protein, Lymphocyte count, Lactate dehydrogenase) score was established using multivariate logistic regression analysis. The HNC-LL score accurately predicted disease severity in the Honghu training cohort (area under the curve [AUC]=0.861, 95% confidence interval [CI]: 0.800-0.922; P<0.001); Honghu internal validation cohort (AUC=0.871, 95% CI: 0.769-0.972; P<0.001); and Nanchang external validation cohort (AUC=0.826, 95% CI: 0.746-0.907; P<0.001) and outperformed other models, including CURB-65 (confusion, uraemia, respiratory rate, BP, age ≥65 years) score model, MuLBSTA (multilobular infiltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hypertension, and age) score model, and neutrophil-to-lymphocyte ratio model. The clinical significance of HNC-LL in accurately predicting the risk of future development of severe COVID-19 was confirmed. INTERPRETATION: We developed an accurate tool for predicting disease severity among COVID-19 patients. This model can potentially be used to identify patients at risks of developing severe disease in the early stage and therefore guide treatment decisions. FUNDING: This work was supported by the National Nature Science Foundation of China (grant no. 81972897) and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2015).


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Índice de Gravidade de Doença , Betacoronavirus , Proteína C-Reativa/análise , Síndrome da Liberação de Citocina/patologia , Feminino , Humanos , Hipertensão/patologia , L-Lactato Desidrogenase/análise , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Pandemias , Prognóstico , Estudos Retrospectivos
15.
J Infect ; 81(4): e18-e25, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32634459

RESUMO

OBJECTIVE: Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment. METHODS: We performed a systematic review with meta-analysis, using five databases to compare the predictors of death for COVID-19, SARS and MERS. A random-effects model meta-analysis calculated odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: 845 articles up through 11/4/2020 were retrieved, but only 28 studies were included in this meta-analysis. The results showed that males had a higher likelihood of death than females (OR = 1.82, 95% CI 1.56-2.13). Age (OR = 7.86, 95% CI 5.46-11.29), diabetes comorbidity (OR = 3.73, 95% CI 2.35-5.90), chronic lung disease (OR = 3.43, 95% CI 1.80-6.52) and hypertension (OR = 3.38, 95% CI 2.45-4.67) were the mortality risk factors. The laboratory indicators lactic dehydrogenase (OR = 37.52, 95% CI 24.68-57.03), C-reactive protein (OR = 12.11, 95% CI 5.24-27.98), and neutrophils (OR = 17.56, 95% CI 10.67-28.90) had stronger correlations with COVID-19 mortality than with SARS or MERS mortality. Consolidation and ground-glass opacity imaging features were similar among COVID-19, SARS, and MERS patients. CONCLUSIONS: COVID-19's mortality factors are similar to those of SARS and MERS. Age and laboratory indicators could be effective predictors of COVID-19 mortality outcomes.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Fatores de Risco , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/mortalidade , Betacoronavirus , Proteína C-Reativa/análise , Diabetes Mellitus/patologia , Feminino , Humanos , Hipertensão/patologia , L-Lactato Desidrogenase/sangue , Pneumopatias/patologia , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio , Neutrófilos/citologia , Pandemias , Vírus da SARS , Fatores Sexuais
16.
Life Sci ; 254: 117788, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: covidwho-260092

RESUMO

AIMS: As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS: A systematic review of the literature was carried out to identify relevant articles using six different databases. Keywords to refine the search included 'COVID-19', 'SARS-CoV2', 'Biomarkers', among others. Only studies which reported data on pre-defined outcomes were included. KEY FINDINGS: Thirty-four relevant articles were identified which reviewed the following biomarkers: C-reactive protein, serum amyloid A, interleukin-6, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, D-dimer, cardiac troponin, renal biomarkers, lymphocytes and platelet count. Of these, all but two, showed significantly higher levels in patients with severe complications of COVID-19 infection compared to their non-severe counterparts. Lymphocytes and platelet count showed significantly lower levels in severe patients compared to non-severe patients. SIGNIFICANCE: Although research is still in its early stages, the discovery of how different biomarkers behave during the course of the disease could help clinicians in identifying severe disease earlier and subsequently improve prognosis. Nevertheless, we urge for more research across the globe to corroborate these findings.


Assuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Betacoronavirus , Biomarcadores , Proteína C-Reativa/análise , Técnicas de Laboratório Clínico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Interleucina-6/sangue , Rim , L-Lactato Desidrogenase/sangue , Contagem de Linfócitos , Neutrófilos/citologia , Pandemias , Contagem de Plaquetas , Prognóstico , Proteína Amiloide A Sérica/análise , Troponina I/sangue
17.
Cytometry A ; 97(8): 772-776, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32542842

RESUMO

A reduced peripheral blood absolute lymphocyte count with an elevated neutrophil count has been a consistent observation in hospitalized coronavirus disease 2019 (COVID-19) patients. In this brief meta-analysis, the reduction of lymphocyte subset counts in COVID-19 patients was investigated across 20 peer-reviewed studies meeting criteria for reporting lymphocyte subset counts and COVID-19 disease severity. CD4+ T cell, CD8+ T cell, B cell, NK cell, and total lymphocyte cell counts all showed statistically significant reduction in patients with severe/critical COVID-19 disease compared to mild/moderate disease. T-cell subsets showed the largest standardized magnitude of change. In some studies, multivariate analysis has shown that CD4 and/or CD8 T-cells counts are independently predictive of patient outcomes. © 2020 International Society for Advancement of Cytometry.


Assuntos
Linfócitos B/citologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Infecções por Coronavirus/sangue , Células Matadoras Naturais/citologia , Pneumonia Viral/sangue , Subpopulações de Linfócitos T/citologia , Betacoronavirus , Humanos , Contagem de Linfócitos , Neutrófilos/citologia , Pandemias
18.
PLoS One ; 15(6): e0232043, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542007

RESUMO

BACKGROUND: Elevated neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in pancreatic cancer. We aim to investigate the association of the various hematologic markers, in particular NLR among others, with distant metastases, a common feature in pancreatic cancer. METHODS: Clinical data from 355 pancreatic cancer patients managed at King Hussein Cancer Center (Amman-Jordan) have been reviewed. We examined the relationship between absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophilic count (AEC), absolute monocytic count (AMC), NLR, monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) with the presence of baseline distant metastases and OS. Receiver Operating Characteristic (ROC) curve analysis was plotted to identify the NLR optimum cutoff value indicative of its association with distant metastases. RESULTS: On univariate and multivariate analyses patients whom on presentation had high NLR (≥3.3) showed more baseline distant metastases compared to patients with low NLR (<3.3), (p-value: <0.0001 and <0.0001, respectively). Patients with high baseline ANC (≥5500/µL), AMC (≥600/µL), MLR (≥0.3) had more baseline distant metastases in comparison to patients with lower values (p-value: 0.02, 0.001, and <0.0001, respectively). High ANC, NLR, MLR, and PLR and low ALC were associated with poorer OS, (p-value: <0.0001, <0.0001, <0.0001, 0.04, and 0.01, respectively). CONCLUSION: This study presents additional evidence of the association of some of the hematologic markers; in particular ANC, NLR, AMC, and MLR, with baseline distant metastases and poor outcome in pancreatic cancer. Whether these immune phenomena can help in identifying patients at higher risk for the subsequent development of distant metastases is unknown.


Assuntos
Linfócitos/citologia , Neutrófilos/citologia , Neoplasias Pancreáticas/patologia , Idoso , Área Sob a Curva , Contagem de Células Sanguíneas , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Curva ROC , Estudos Retrospectivos
19.
BMC Infect Dis ; 20(1): 396, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503442

RESUMO

BACKGROUND: Delayed antifungal therapy for candidemia leads to increased mortality. Differentiating bacterial infection from candidemia in systemic inflammatory response syndrome (SIRS) patients is complex and difficult. The Delta Neutrophil Index (DNI) has recently been considered a new factor to distinguish infections from non-infections and predict the severity of sepsis. We aimed to assess if the DNI can predict and provide a prognosis for candidemia in SIRS patients. METHODS: A matched case-control study was conducted from July 2016 to June 2017 at Kangdong Sacred Heart Hospital. Among patients with a comorbidity of SIRS, those with candidemia were classified as the case group, whereas those with negative blood culture results were classified as the control group. The matching conditions included age, blood culture date, and SIRS onset location. Multivariate logistic regression was performed to evaluate DNI as a predictive and prognostic factor for candidemia. RESULTS: The 140 included patients were assigned to each group in a 1:1 ratio. The DNI_D1 values measured on the blood culture date were higher in the case group than in the control group (p <  0.001). The results of multivariate analyses confirmed DNI_D1 (odds ratio [ORs] 2.138, 95% confidential interval [CI] 1.421-3.217, p <  0.001) and Candida colonization as predictive factors for candidemia. The cutoff value of DNI for predicting candidemia was 2.75%. The area under the curve for the DNI value was 0.804 (95% CI, 0.719-0.890, p < 0.001), with a sensitivity and specificity of 72.9 and 78.6%, respectively. Analysis of 14-day mortality in patients with candidemia showed significantly higher DNI_D1 and DNI_48 in the non-survivor group than in the survivor group. CONCLUSIONS: DNI was identified as a predictive factor for candidemia in patients with SIRS and a prognostic factor in predicting 14-day mortality in candidemia patients. DNI, along with clinical patient characteristics, was useful in determining the occurrence of candidemia in patients with SIRS.


Assuntos
Candidemia/diagnóstico , Neutrófilos/citologia , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Candida/isolamento & purificação , Candidemia/complicações , Candidemia/microbiologia , Candidemia/mortalidade , Estudos de Casos e Controles , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
20.
Arch Biochem Biophys ; 689: 108465, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32561201

RESUMO

Neutrophil extracellular traps (NETs) occur during the development of autoimmune diseases, cancer and diabetes. A novel form of cell death that is induced by NETs is called NETosis. Although these diseases are known to have an epigenetic component, epigenetic regulation of NETosis has not previously been explored. In the present study, we investigated the effects of epigenetic change, especially DNA demethylation, on NETosis in neutrophil-like cells differentiated from HL-60 cells, which were incubated for 72 h in the presence of 1.25% DMSO. DMSO-differentiated neutrophil-like cells tended to have increased methylation of genomic DNA. NETosis in the neutrophil-like cells was induced by the treatment with A23187, calcium ionophore, and increased by the addition of the DNMT inhibitor 5-azacytidine (Aza) during differentiation. Interestingly, Aza-stimulated neutrophil-like cell induced NETosis without treatment with A23187. Although reactive oxygen species (ROS), especially superoxide and hypochlorous acid, are important in NETosis induction, treatment with Aza decreased production of ROS, while mitochondria ROS scavenger tended to decrease Aza-induced NETosis. Moreover, the genomic DNA in Aza-stimulated neutrophil-like cell was demethylated, and the expression of peptidylarginine deiminase4 (PAD4) and citrullinated histone H3 (R2+R8+R17) was increased, but myeloperoxidase expression was unaffected. Additionally, PAD4 inhibition tended to decrease Aza-induced NETosis. The DNA demethylation induced by the DNMT inhibitor in neutrophil-like cells enhanced spontaneous NETosis through increasing PAD4 expression and histone citrullination. This study establishes a relationship between NETosis and epigenetics for the first time, and indicates that various diseases implicated to have an epigenetic component might be exacerbated by excessive NETosis also under epigenetic control.


Assuntos
Morte Celular , Desmetilação do DNA , Armadilhas Extracelulares/genética , Neutrófilos/citologia , Diferenciação Celular , DNA/genética , Epigênese Genética , Células HL-60 , Humanos , Neutrófilos/metabolismo
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