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1.
Mediators Inflamm ; 2020: 8198963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029105

RESUMO

The novel coronavirus is not only causing respiratory problems, but it may also damage the heart, kidneys, liver, and other organs; in Wuhan, 14 to 30% of COVID-19 patients have lost their kidney function and now require either dialysis or kidney transplants. The novel coronavirus gains entry into humans by targeting the ACE2 receptor that found on lung cells, which destroy human lungs through cytokine storms, and this leads to hyperinflammation, forcing the immune cells to destroy healthy cells. This is why some COVID-19 patients need intensive care. The inflammatory chemicals released during COVID-19 infection cause the liver to produce proteins that defend the body from infections. However, these proteins can cause blood clotting, which can clog blood vessels in the heart and other organs; as a result, the organs are deprived of oxygen and nutrients which could ultimately lead to multiorgan failure and consequent progression to acute lung injury, acute respiratory distress syndrome, and often death. However, there are novel protein modification tools called the QTY code, which are similar in their structure to antibodies, which could provide a solution to excess cytokines. These synthetic proteins can be injected into the body to bind the excess cytokines created by the cytokine storm; this will eventually remove the excessive cytokines and inhibit the severe symptoms caused by the COVID-19 infection. In this review, we will focus on cytokine storm in COVID-19 patients, their impact on the body organs, and the potential treatment by QTY code-designed detergent-free chemokine receptors.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/terapia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Receptores de Quimiocinas/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/imunologia , Citocinas/antagonistas & inibidores , Desenho de Fármacos , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Modelos Moleculares , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/terapia , Pandemias , Pneumonia Viral/terapia , Engenharia de Proteínas , Modificação Traducional de Proteínas , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo
2.
Respir Res ; 21(1): 245, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962703

RESUMO

BACKGROUND: The COVID-19 pandemic has led to more than 760,000 deaths worldwide (correct as of 16th August 2020). Studies suggest a hyperinflammatory response is a major cause of disease severity and death. Identitfying COVID-19 patients with hyperinflammation may identify subgroups who could benefit from targeted immunomodulatory treatments. Analysis of cytokine levels at the point of diagnosis of SARS-CoV-2 infection can identify patients at risk of deterioration. METHODS: We used a multiplex cytokine assay to measure serum IL-6, IL-8, TNF, IL-1ß, GM-CSF, IL-10, IL-33 and IFN-γ in 100 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton (UK). Demographic, clinical and outcome data were collected for analysis. RESULTS: Age > 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). IL-6, IL-8, TNF, IL-1ß and IL-33 were significantly associated with adverse outcome. Clinical parameters were predictive of poor outcome (AUROC 0.71), addition of a combined cytokine panel significantly improved the predictability (AUROC 0.85). In those ≤70 years, IL-33 and TNF were predictive of poor outcome (AUROC 0.83 and 0.84), addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs 0.77). CONCLUSIONS: A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Citocinas/análise , Mortalidade Hospitalar , Mediadores da Inflamação/sangue , Pandemias/estatística & dados numéricos , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Fatores Etários , Análise de Variância , Área Sob a Curva , Técnicas de Laboratório Clínico/métodos , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Feminino , Hospitalização/estatística & dados numéricos , Hospitais Universitários , Humanos , Incidência , Masculino , Pandemias/prevenção & controle , Fenótipo , Pneumonia Viral/fisiopatologia , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Reino Unido
3.
J Nippon Med Sch ; 87(4): 240-242, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908116

RESUMO

OBJECTIVE: Little is known about COVID-19 patients who have not traveled to infected areas or had direct contact with infected persons. This report describes the clinical features of 28 such patients with confirmed COVID-19 infection. METHODS: Data on clinical characteristics during hospitalization were collected. RESULTS: Epidemiological exposures were investigated among patients reporting no travel to infected areas or direct contact with a case-patient. Patients presented with various symptoms, increased levels of inflammatory markers, and consolidation or ground-glass opacification on computed tomography scans. CONCLUSIONS: The present report contributes critical information on the clinical presentation of COVID-19 patients without typical epidemiological exposures.


Assuntos
Betacoronavirus/patogenicidade , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Adulto , Idoso , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Feminino , Hospitalização , Interações entre Hospedeiro e Microrganismos , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Valor Preditivo dos Testes , Fatores de Risco , Tomografia Computadorizada por Raios X
4.
Sci Immunol ; 5(51)2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943497

RESUMO

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Monócitos/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Ciclo-Oxigenase 2/imunologia , Ciclo-Oxigenase 2/metabolismo , Progressão da Doença , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Antígeno Ki-67/imunologia , Antígeno Ki-67/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Reino Unido/epidemiologia
5.
Biochem Med (Zagreb) ; 30(3): 030503, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32774121

RESUMO

The new corona virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) causes a disease called COVID-19 (coronavirus disease 2019), that develops mostly in subjects with already impaired immune system function, primarily in the elderly and in individuals with some chronic disease or condition. The reasons for this should be sought in the processes of aging and chronic latent inflammation, i.e. immunosenescence and inflammaging. Laboratory medicine specialists are currently focused on proving the presence of the virus and defining biomarkers that would enable the prediction of disease progression. For now, it has been shown that useful biomarkers can include general biomarkers of inflammation (parameters of complete blood count, C-reactive protein, interleukin-6, procalcitonin), biomarkers of myocardial damage (high sensitivity troponin I/T, B-type natriuretic peptide, and N-terminal B type natriuretic peptide), and vascular biomarkers (D-dimer, prothrombin time, fibrinogen). Their actual diagnostic specificity, sensitivity and predictive value need to be tested on a larger number of subjects. In addition, it is important to find and evaluate specific biomarkers of immunosenescence.


Assuntos
Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/normas , Infecções por Coronavirus/sangue , Pessoal de Saúde/normas , Mediadores da Inflamação/sangue , Pneumonia Viral/sangue , Manejo de Espécimes/normas , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/metabolismo , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/metabolismo , Manejo de Espécimes/métodos
6.
Ann Clin Lab Sci ; 50(4): 528-535, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32826251

RESUMO

The COVID-19 outbreak has had a high impact on diagnostic laboratory services recently. The current literature has focused on reviewing tests that are specifically related to the diagnosis of COVIDS-19 infection using either molecular testing or immunoassays detecting viral antigens or antibodies. In this short communication review, we aimed to summarize the most common non-specific laboratory tests that may be requested in patients with suspected COVID-19 infection to help in the assessment of different organs and other vital laboratory tests to avoid complications as a consequence of COVID-19 infection.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Biomarcadores/sangue , Contagem de Células Sanguíneas , Análise Química do Sangue , Testes de Coagulação Sanguínea , Gasometria , Infecções por Coronavirus/sangue , Infecções por Coronavirus/urina , Citocinas/sangue , Humanos , Mediadores da Inflamação/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/urina
7.
BMC Cardiovasc Disord ; 20(1): 373, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32799852

RESUMO

BACKGROUND: Hypertension is the most frequent co-morbidity in patients with covid-19 infection, and we might speculate that a specific blood group could play a key role in the clinical outcome of hypertensive patients with covid-19. METHODS: In this prospective study, we compared 0 vs. non-0 blood group in hypertensive patients with covid-19 infection. In these patients, we evaluated inflammatory and thrombotic status, cardiac injury, and death events. RESULTS: Patients in non-0 (n = 92) vs. 0 blood group (n = 72) had significantly different values of activated pro-thrombin time, D-dimer, and thrombotic indexes as Von Willebrand factor and Factor VIII (p < 0.05). Furthermore, patients in non-0 vs. 0 blood group had higher rate of cardiac injury (10 (13.9%) vs. 27 (29.3%)) and death, (6 (8.3%) vs. 18 (19.6%)), (p < 0.05). At the multivariate analysis, Interleukin-6 (1.118, CI 95% 1.067-1.171) and non-0 blood group (2.574, CI 95% 1.207-5.490) were independent predictors of cardiac injury in hypertensive patients with covid-19. D-dimer (1.082, CI 95% 1.027-1.140), Interleukin-6 (1.216, CI 95% 1.082-1.367) and non-0 blood group (3.706, CI 95% 1.223-11.235) were independent predictors of deaths events in hypertensive patients with covid-19. CONCLUSIONS: Taken together, our data indicate that non-0 covid-19 hypertensive patients have significantly higher values of pro-thrombotic indexes, as well as higher rate of cardiac injury and deaths compared to 0 patients. Moreover, AB0 blood type influences worse prognosis in hypertensive patients with covid-19 infection.


Assuntos
Sistema ABO de Grupos Sanguíneos , Betacoronavirus/patogenicidade , Pressão Sanguínea , Infecções por Coronavirus/sangue , Hipertensão/sangue , Pneumonia Viral/sangue , Adulto , Idoso , Biomarcadores/sangue , Coagulação Sanguínea , Fatores de Coagulação Sanguínea/análise , Estudos de Casos e Controles , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Mediadores da Inflamação/sangue , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Estudos Prospectivos , Fatores de Risco
8.
Life Sci ; 258: 118222, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768577

RESUMO

AIMS: We previously reported that fenugreek-derived 4-hydroxyisoleucine ameliorates insulin resistance via regulation of TNF-α converting enzyme (TACE) expression. In the present study, we further investigate the effects and mechanisms of fenugreek on obesity-induced inflammation and insulin signaling in the high-fat diet (HFD)-challenged obese mice. MAIN METHODS: After 12 weeks of HFD intervention, mice were treated with the low or high dosages of fenugreek. Serum levels of glucose, insulin, lipid profile, inflammation cytokines, and adipokines were detected. Macrophage infiltration and adipose tissue morphology were observed. Western blot was conducted to investigate the expressions of inactive rhomboid 2 (iRhom2) and TACE as well as other signaling pathways in subcutaneous adipose tissue. KEY FINDINGS: We showed that fenugreek significantly suppressed body weight gain and fat accumulation in HFD-challenged obese mice. Meanwhile, fasting glucose, insulin, and HOMA-IR in fenugreek-treated mice were remarkably decreased, which were properly explained by fenugreek-induced activation of the insulin receptor signaling pathway. Moreover, the anti-inflammatory properties of fenugreek were shown by the decrease of systemic and local expressions of pro-inflammatory cytokines as well as reduced macrophage infiltration into adipose tissue. Additionally, fenugreek markedly deactivated NF-κB and JNK pathways. Finally, we demonstrated that fenugreek strikingly repressed the transcriptions and expressions of iRhom2 and TACE. SIGNIFICANCE: Fenugreek shows an encouraging and promising property in ameliorating insulin resistance and suppressing inflammation in obesity, which might be realized by fenugreek-mediated inhibition of iRhom2/TACE axis-facilitated TNF-α release from adipocytes.


Assuntos
Proteína ADAM17/antagonistas & inibidores , Proteínas de Transporte/antagonistas & inibidores , Mediadores da Inflamação/antagonistas & inibidores , Resistência à Insulina/fisiologia , Obesidade/tratamento farmacológico , Trigonella , Proteína ADAM17/sangue , Animais , Proteínas de Transporte/sangue , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Inflamação/sangue , Inflamação/tratamento farmacológico , Mediadores da Inflamação/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sementes
9.
Science ; 369(6508): 1210-1220, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32788292

RESUMO

Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators-including EN-RAGE, TNFSF14, and oncostatin M-which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Citocinas/sangue , DNA Bacteriano/sangue , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Citometria de Fluxo , Antígenos HLA-DR/análise , Humanos , Imunidade , Imunidade Inata , Imunoglobulinas/sangue , Imunoglobulinas/imunologia , Mediadores da Inflamação/sangue , Interferon Tipo I/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/sangue , Masculino , Células Mieloides/imunologia , Células Mieloides/metabolismo , Pandemias , Transdução de Sinais , Análise de Célula Única , Biologia de Sistemas , Serina-Treonina Quinases TOR/metabolismo , Transcrição Genética , Transcriptoma
10.
PLoS One ; 15(8): e0237074, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790694

RESUMO

Androgen dependent tissue factor pathway inhibitor regulating protein (ADTRP) is a novel protein associated with coronary artery disease (CAD) susceptibility, and reduced mRNA expression of ADTRP was shown to be associated with increased CAD risk. This study aimed to determine and compare circulating ADTRP levels between CAD patients and controls, and to test the performance of plasma ADTRP as a biomarker for CAD. We measured plasma ADTRP, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high sensitivity-C reactive protein (hs-CRP) levels in 362 CAD patients, 150 angiographically negative CAD controls, and 83 healthy adults with no known clinical or medical conditions using commercial ELISA. Statistical analyses were performed using receiver operator characteristic (ROC) curves, quantile regression and logistic regression, with adjustments for age, gender, ethnicity and BMI. CAD patients had significantly lower plasma ADTRP levels 1,545 (1,087-2,408) pg/ml as compared to CAD controls 2,259 (1,533-3,778) pg/ml and healthy adults 3,904 (2,732-5,463) pg/ml. Plasma ADTRP outperformed the other three inflammatory biomarkers (TNF-α, IL-6 and hs-CRP) for CAD (Area under ROC curve: 0.67, Odds ratio (OR): 0.907). Our study has shown for the first time that ADTRP is present in circulation, and that plasma ADTRP may be a novel independent biomarker for CAD.


Assuntos
Doença da Artéria Coronariana/sangue , Proteínas de Membrana/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Fator de Necrose Tumoral alfa/sangue
12.
Int J Nanomedicine ; 15: 4139-4149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606669

RESUMO

Introduction: A correlation is established between the efficacy of Chinese herbal medicine and its charcoal drugs. Lonicerae japonicae Flos (LJF) is commonly used to treat fever, carbuncle, and tumors, among others. LJF Carbonisatas (LJFC) is preferred for detoxifying and relieving dysentery and its related symptoms. However, the mechanisms underlying the effects of LJFC remain unknown. Aim: The aim of this study was to explore the effects of LJFC-derived carbon dots (LJFC-CDs) on lipopolysaccharide (LPS)-induced fever and hypothermia rat models. Methods: LJFC-CDs were characterized using transmission electron microscopy, high-resolution transmission electron microscopy, Fourier-transform infrared, ultraviolet, fluorescence, X-ray photoelectron spectroscopy, X-ray diffraction and high-performance liquid chromatography. The anti-inflammatory effects of LJFC-CDs were evaluated and confirmed using rat models of LPS-induced fever or hypothermia. Results: The LJFC-CDs ranged from 1.0 to 10.0 nm in diameter, with a yield of 0.5%. LJFC-CDs alleviated LPS-induced inflammation, as demonstrated by the expression of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 and the recovery of normal body temperature. Conclusion: LJFC-CDs may have an anti-inflammatory effect and a potential to alleviate fever and hypothermia caused by inflammation.


Assuntos
Carbono/química , Febre/tratamento farmacológico , Hipotermia/tratamento farmacológico , Lonicera/química , Extratos Vegetais/uso terapêutico , Animais , Temperatura Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , AMP Cíclico/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Mediadores da Inflamação/sangue , Lipopolissacarídeos , Masculino , Camundongos , Extratos Vegetais/toxicidade , Células RAW 264.7 , Ratos Sprague-Dawley , Espectrometria de Fluorescência
13.
Biomark Med ; 14(12): 1091-1097, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32677844

RESUMO

Aim: To describe the association between D-dimer, CRP, IL-6, ferritin, LDH and the clinical outcomes in a cohort of 299 COVID-19 patients treated on the inpatient medical service at a university hospital in the District of Columbia (DC, USA). Methodology & results: In this retrospective study, we included all laboratory confirmed COVID-19 adults admitted to the inpatient medicine service at the George Washington University Hospital between 12 March 2020 and 9 May 2020. We analyzed the association of biomarkers on intensive care unit transfer, intubation and mortality. Threshold values for all biomarkers were found to be statistically significant and independently associated with higher odds of clinical deterioration and death. Conclusion: Laboratory markers of inflammation and coagulopathy can help clinicians identify patients who are at high risk for clinical deterioration in COVID-19.


Assuntos
Betacoronavirus , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Adulto , Proteína C-Reativa/metabolismo , Técnicas de Laboratório Clínico , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , District of Columbia/epidemiologia , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Mediadores da Inflamação/sangue , Unidades de Terapia Intensiva , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
14.
J Thromb Thrombolysis ; 50(3): 499-511, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32700024

RESUMO

The COVID-19 pandemic now totaling 13,000,000 cases and over 571,000 deaths has continued to teach the medical, scientific and lay communities about viral infectious disease in the modern era. Among the many lessons learned for the medical community is the potential for transmissibility and host infectivity of the SARS-CoV-2 virus. Moreover, it has become clear that the virus can affect any organ including the circulatory system, directly via either tissue tropism or indirectly stemming from inflammatory responses in the form of innate immunity, leukocyte debris such as cell-free DNA and histones and RNA viral particles. The following review considers COVID-19-associated vasculitis and vasculopathy as a defining feature of a virus-induced systemic disease with acute, subacute and potential chronic health implications.


Assuntos
Betacoronavirus/patogenicidade , Vasos Sanguíneos/virologia , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Vasculite/virologia , Animais , Betacoronavirus/imunologia , Coagulação Sanguínea , Vasos Sanguíneos/imunologia , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Prognóstico , Fatores de Risco , Vasculite/diagnóstico , Vasculite/imunologia , Vasculite/fisiopatologia
15.
Arterioscler Thromb Vasc Biol ; 40(9): 2159-2170, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32673527

RESUMO

OBJECTIVE: Evidence from preclinical and clinical studies has demonstrated that myocardial infarction promotes atherosclerosis progression. The impact of focal vascular inflammation on the progression and phenotype of remote atherosclerosis remains unknown. Approach and Results: We used a novel ApoE-/- knockout mouse model of sustained arterial inflammation, initiated by mechanical injury in the abdominal aorta. Using serial in vivo molecular MRI and ex vivo histology and flow cytometry, we demonstrate that focal arterial inflammation triggered by aortic injury, accelerates atherosclerosis in the remote brachiocephalic artery. The brachiocephalic artery atheroma had distinct histological features including increased plaque size, plaque permeability, necrotic core to collagen ratio, infiltration of more inflammatory monocyte subsets, and reduced collagen content. We also found that arterial inflammation following focal vascular injury evoked a prolonged systemic inflammatory response manifested as a persistent increase in serum IL-6 (interleukin 6). Finally, we demonstrate that 2 therapeutic interventions-pravastatin and minocycline-had distinct anti-inflammatory effects at the plaque and systemic level. CONCLUSIONS: We show for the first time that focal arterial inflammation in response to vascular injury enhances systemic vascular inflammation, accelerates remote atheroma progression and induces plaques more inflamed, lipid-rich, and collagen-poor in the absence of ischemic myocardial injury. This inflammatory cascade is modulated by pravastatin and minocycline treatments, which have anti-inflammatory effects at both plaque and systemic levels that mitigate atheroma progression.


Assuntos
Aortite/complicações , Aterosclerose/etiologia , Tronco Braquiocefálico/metabolismo , Mediadores da Inflamação/sangue , Placa Aterosclerótica , Animais , Anti-Inflamatórios/farmacologia , Aortite/sangue , Aortite/patologia , Aterosclerose/sangue , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Tronco Braquiocefálico/efeitos dos fármacos , Tronco Braquiocefálico/patologia , Colágeno/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Interleucina-6/sangue , Metabolismo dos Lipídeos , Masculino , Camundongos Knockout para ApoE , Minociclina/farmacologia , Necrose , Pravastatina/farmacologia , Fatores de Tempo
16.
Arterioscler Thromb Vasc Biol ; 40(9): 2322-2331, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32698688

RESUMO

OBJECTIVE: Inflammatory markers, such as hs-CRP (high-sensitivity C-reactive protein), have been reported to be related to peripheral artery disease (PAD). Galectin-3, a biomarker of fibrosis, has been linked to vascular remodeling and atherogenesis. However, its prospective association with incident PAD is unknown; as is the influence of inflammation on the association between galectin-3 and PAD. Approach and Results: In 9851 Atherosclerosis Risk in Communities Study participants free of PAD at baseline (1996-1998), we quantified the association of galactin-3 and hs-CRP with incident PAD (hospitalizations with PAD diagnosis [International Classification of Diseases-Ninth Revision: 440.2-440.4] or leg revascularization [eg, International Classification of Diseases-Ninth Revision: 38.18]) as well as its severe form, critical limb ischemia (PAD cases with resting pain, ulcer, gangrene, or leg amputation) using Cox models. Over a median follow-up of 17.4 years, there were 316 cases of PAD including 119 critical limb ischemia cases. Log-transformed galectin-3 was associated with incident PAD (adjusted hazard ratio, 1.17 [1.05-1.31] per 1 SD increment) and critical limb ischemia (1.25 [1.05-1.49] per 1 SD increment). The association was slightly attenuated after further adjusting for hs-CRP (1.14 [1.02-1.27] and 1.22 [1.02-1.45], respectively). Log-transformed hs-CRP demonstrated robust associations with PAD and critical limb ischemia even after adjusting for galectin-3 (adjusted hazard ratio per 1 SD increment 1.34 [1.18-1.52] and 1.34 [1.09-1.65], respectively). The addition of galectin-3 and hs-CRP to traditional atherosclerotic predictors (C statistic of the base model 0.843 [0.815-0.871]) improved the risk prediction of PAD (ΔC statistics, 0.011 [0.002-0.020]). CONCLUSIONS: Galectin-3 and hs-CRP were independently associated with incident PAD in the general population, supporting the involvement of fibrosis and inflammation in the pathophysiology of PAD.


Assuntos
Proteína C-Reativa/análise , Galectina 3/sangue , Mediadores da Inflamação/sangue , Claudicação Intermitente/sangue , Isquemia/sangue , Doença Arterial Periférica/sangue , Idoso , Biomarcadores/sangue , Estado Terminal , Feminino , Fibrose , Humanos , Incidência , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/epidemiologia , Claudicação Intermitente/terapia , Isquemia/diagnóstico , Isquemia/epidemiologia , Isquemia/terapia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/terapia , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos
17.
Crit Care ; 24(1): 360, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32552865

RESUMO

Thrombotic complications and coagulopathy frequently occur in COVID-19. However, the characteristics of COVID-19-associated coagulopathy (CAC) are distinct from those seen with bacterial sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC), with CAC usually showing increased D-dimer and fibrinogen levels but initially minimal abnormalities in prothrombin time and platelet count. Venous thromboembolism and arterial thrombosis are more frequent in CAC compared to SIC/DIC. Clinical and laboratory features of CAC overlap somewhat with a hemophagocytic syndrome, antiphospholipid syndrome, and thrombotic microangiopathy. We summarize the key characteristics of representative coagulopathies, discussing similarities and differences so as to define the unique character of CAC.


Assuntos
Betacoronavirus , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Transtornos da Coagulação Sanguínea/sangue , Testes de Coagulação Sanguínea/métodos , Infecções por Coronavirus/sangue , Humanos , Mediadores da Inflamação/sangue , Pandemias , Agregação Plaquetária/fisiologia , Pneumonia Viral/sangue
18.
Biomed Res Int ; 2020: 7413673, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32596365

RESUMO

Some patients with coronavirus disease 2019 (COVID-19) show abnormal changes in laboratory myocardial injury markers, suggesting that patients with myocardial injury have a higher mortality rate than those without myocardial injury. This article reviews the possible mechanism of myocardial injury in patients with COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the patients with COVID-19 in aspects of direct infection of myocardial injury, specific binding to functional receptors on cardiomyocytes, and immune-mediated myocardial injury. During hospitalization, the monitoring of laboratory myocardial injury markers in patients of COVID-19 should be strengthened.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/etiologia , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Biomarcadores/sangue , Biomarcadores/metabolismo , Infecções por Coronavirus/metabolismo , Citocinas/sangue , Citocinas/imunologia , Traumatismos Cardíacos/metabolismo , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Modelos Cardiovasculares , Modelos Imunológicos , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/metabolismo , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/metabolismo
19.
Medicine (Baltimore) ; 99(22): e20346, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481414

RESUMO

The immune system plays a fundamental role in the response to neoadjuvant chemotherapy (NAC) of locally advanced breast cancer (LABC) patients. Patients with pathological complete response (pCR) after NAC have a higher survival rate. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are peripheral blood indicators of inflammatory response. This investigates the correlation between NLR, PLR, LMR, and other clinicopathological features of breast cancer patients before receiving NAC and pCR.Data of LABC patients who underwent NAC between 2009 and 2018 were retrospectively reviewed. Each patient's peripheral complete blood count was recorded before starting NAC. The cut-off values for neutrophils, lymphocytes, monocytes, and platelets in the peripheral blood and NLR, PLR, and LMR were determined by receiver operating characteristic curve analyses.The records of 131 patients were analyzed and divided into two groups, pCR (+ve) and pCR (-ve), and their clinicopathological features and laboratory findings were compared. pCR was achieved in 23.6% of patients. The cut-off values of neutrophils, lymphocytes, monocytes, and platelets at the time of diagnosis and NLR, PLR, and LMR were, respectively, 4150 µL, 2000 µL, 635 µL, 271 × 10 µL, 1.95, 119, and 3.35. The pCR rate was higher in patients with low neutrophil count, low NLR, and high lymphocyte count (P = .002, <.001, and .040, respectively).As per the findings of multivariate logistic regression analysis, the independent predictive factors of pCR were clinical tumor size T1 and T2, grade 3, ER negativity, and low NLR (P = .015, .001, .020, .022, and .001, respectively).While NLR was found to be an independent predictive factor of pCR in LABC patients receiving NAC, a similar result was not observed for PLR and LMR. NLR can be a useful biomarker for predicting the response of patients receiving NAC.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Mediadores da Inflamação/sangue , Adulto , Idoso , Biomarcadores Tumorais , Plaquetas/metabolismo , Quimioterapia Adjuvante , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Linfócitos/metabolismo , Pessoa de Meia-Idade , Monócitos/metabolismo , Neutrófilos/metabolismo , Estudos Retrospectivos , Análise de Sobrevida
20.
Niger J Clin Pract ; 23(6): 817-824, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32525117

RESUMO

Background: The Global Initiative classification (GOLD) for chronic obstructive pulmonary disease (COPD), which relies on the practical issues of treatment of this complex and heterogeneous disease, may not be reliable in predicting disease severity and prognosis as the term of inflammation is excluded from the definition. Aim: The aim of this study was to determine systemic inflammatory markers in GOLD ABCD groups and to compare these parameters according to clinical and functional features. Methods: The study included 60 COPD patients and 59 healthy subjects. Comparisons were made with the pulmonary function test, transthoracic echocardiography and the six-minute walk test (6MWT). The COPD assessment test (CAT), modified Medical Research Council (mMRC), and index scores of body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) were recorded. The systemic inflammatory state was assessed using C-reactive protein, fibrinogen, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-18. Results: The levels of all serum inflammatory markers were higher in the COPD group than in the control group. TNF-α and IL-6 were significantly higher in the symptomatic groups (B and D) than in the less symptomatic groups (A and C) (P < 0.05). Spirometric parameters were more severe in Group D, followed by groups C, B and A, respectively. The 6MWT and the BODE scores were worst in Group D, followed by groups B, C and A. Conclusion: The results suggest that bronchodilator treatment alone might be insufficient in Group B patients, as the systemic inflammatory markers in addition to exercise capacity and mortality predictors were at the worst level in Groups D and B.


Assuntos
Biomarcadores/sangue , Mediadores da Inflamação/sangue , Inflamação/sangue , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , Índice de Massa Corporal , Proteína C-Reativa , Estudos de Casos e Controles , Estudos Transversais , Dispneia/fisiopatologia , Ecocardiografia , Tolerância ao Exercício , Feminino , Humanos , Inflamação/imunologia , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória , Índice de Gravidade de Doença , Espirometria , Fator de Necrose Tumoral alfa/sangue , Teste de Caminhada
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