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1.
BMJ Open ; 10(11): e039951, 2020 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-33191263

RESUMO

INTRODUCTION: About 25% of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) associated with a high release of pro-inflammatory cytokines such as interleukin-6 (IL-6). The aim of the SARICOR study is to demonstrate that early administration of sarilumab (an IL-6 receptor inhibitor) in hospitalised patients with COVID-19, pulmonary infiltrates and a high IL-6 or D-dimer serum level could reduce the progression of ARDS requiring high-flow nasal oxygen or mechanical ventilation (non-invasive or invasive). METHODS AND ANALYSIS: Phase II, open-label, randomised, multicentre, controlled clinical trial to study the efficacy and safety of the administration of two doses of sarilumab (200 and 400 mg) plus best available therapy (BAT) in hospitalised adults with COVID-19 presenting cytokine release syndrome. This strategy will be compared with a BAT control group. The efficacy and safety will be monitored up to 28 days postadministration. A total of 120 patients will be recruited (40 patients in each arm). ETHICS AND DISSEMINATION: The clinical trial has been approved by the Research Ethics Committee of the coordinating centre and authorised by the Spanish Agency of Medicines and Medical Products. If the hypothesis is verified, the dissemination of the results could change clinical practice by increasing early administration of sarilumab in adult patients with COVID-19 presenting cytokine release syndrome, thus reducing intensive care unit admissions. TRIAL REGISTRATION NUMBER: NCT04357860.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Adolescente , Adulto , Idoso , Betacoronavirus , Ensaios Clínicos Fase II como Assunto , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/imunologia , Adulto Jovem
2.
Sci Rep ; 10(1): 17524, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067568

RESUMO

Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. The epidemiological and clinical course of COVID-19 patients has been reported, but there have been few analyses about the characteristics, predictive risk factors, and outcomes of critical patients. In this single-center retrospective case-control study, 90 adult inpatients hospitalized at Tongji Hospital (Wuhan, China) were included. Demographic, clinical, laboratory tests, and treatment data were obtained and compared between critical and non-critical patients. We found that compared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP), and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid, and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical course. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application, and anticoagulation may be beneficial for patient survival.


Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Idoso , Betacoronavirus/isolamento & purificação , Estudos de Casos e Controles , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Mortalidade Hospitalar , Humanos , Interleucina-6/metabolismo , Estimativa de Kaplan-Meier , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Escores de Disfunção Orgânica , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
4.
Arterioscler Thromb Vasc Biol ; 40(11): 2764-2775, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32907371

RESUMO

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can infect patients in any age group including those with no comorbid conditions. Understanding the demographic, clinical, and laboratory characteristics of these patients is important toward developing successful treatment strategies. Approach and Results: In a retrospective study design, consecutive patients without baseline comorbidities hospitalized with confirmed COVID-19 were included. Patients were subdivided into ≤55 and >55 years of age. Predictors of in-hospital mortality or mechanical ventilation were analyzed in this patient population, as well as subgroups. Stable parameters in overall and subgroup models were used to construct a cluster model for phenotyping of patients. Of 1207 COVID-19-positive patients, 157 met the study criteria (80≤55 and 77>55 years of age). Most reliable predictors of outcomes overall and in subgroups were age, initial and follow-up d-dimer, and LDH (lactate dehydrogenase) levels. Their predictive cutoff values were used to construct a cluster model that produced 3 main clusters. Cluster 1 was a low-risk cluster and was characterized by younger patients who had low thrombotic and inflammatory features. Cluster 2 was intermediate risk that also consisted of younger population that had moderate level of thrombosis, higher inflammatory cells, and inflammatory markers. Cluster 3 was a high-risk cluster that had the most aggressive thrombotic and inflammatory feature. CONCLUSIONS: In healthy patient population, COVID-19 remains significantly associated with morbidity and mortality. While age remains the most important predictor of in-hospital outcomes, thromboinflammatory interactions are also associated with worse clinical outcomes regardless of age in healthy patients.


Assuntos
Betacoronavirus/patogenicidade , Regras de Decisão Clínica , Infecções por Coronavirus/virologia , Admissão do Paciente , Pneumonia Viral/virologia , Tromboembolia/virologia , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Nível de Saúde , Mortalidade Hospitalar , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Fenótipo , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Valor Preditivo dos Testes , Prognóstico , Respiração Artificial , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tromboembolia/diagnóstico , Tromboembolia/mortalidade , Tromboembolia/terapia
5.
Eur Respir J ; 56(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32907890

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose to venous thromboembolism. We determined factors independently associated with computed tomography pulmonary angiography (CTPA)-confirmed pulmonary embolism (PE) in hospitalised severe COVID-19 patients. METHODS: Among all (n=349) patients hospitalised for COVID-19 in a university hospital in a French region with a high rate of COVID-19, we analysed patients who underwent CTPA for clinical signs of severe disease (oxygen saturation measured by pulse oximetry ≤93% or breathing rate ≥30 breaths·min-1) or rapid clinical worsening. Multivariable analysis was performed using Firth penalised maximum likelihood estimates. RESULTS: 162 (46.4%) patients underwent CTPA (mean±sd age 65.6±13.0 years; 67.3% male (95% CI 59.5-75.5%). PE was diagnosed in 44 (27.2%) patients. Most PEs were segmental and the rate of PE-related right ventricular dysfunction was 15.9%. By multivariable analysis, the only two significant predictors of CTPA-confirmed PE were D-dimer level and the lack of any anticoagulant therapy (OR 4.0 (95% CI 2.4-6.7) per additional quartile and OR 4.5 (95% CI 1.1-7.4), respectively). Receiver operating characteristic curve analysis identified a D-dimer cut-off value of 2590 ng·mL-1 to best predict occurrence of PE (area under the curve 0.88, p<0.001, sensitivity 83.3%, specificity 83.8%). D-dimer level >2590 ng·mL-1 was associated with a 17-fold increase in the adjusted risk of PE. CONCLUSION: Elevated D-dimers (>2590 ng·mL-1) and absence of anticoagulant therapy predict PE in hospitalised COVID-19 patients with clinical signs of severity. These data strengthen the evidence base in favour of systematic anticoagulation, and suggest wider use of D-dimer guided CTPA to screen for PE in acutely ill hospitalised patients with COVID-19.


Assuntos
Anticoagulantes/administração & dosagem , Infecções por Coronavirus/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Pneumonia Viral/complicações , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Idoso , Betacoronavirus , Angiografia por Tomografia Computadorizada , Infecções por Coronavirus/epidemiologia , Feminino , França/epidemiologia , Humanos , Masculino , Oximetria , Pandemias , Pneumonia Viral/epidemiologia , Valor Preditivo dos Testes , Embolia Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade
6.
Semin Thromb Hemost ; 46(7): 807-814, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32882720

RESUMO

The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis. Coagulopathy has been reported as associated with mortality in people with COVID-19 and is partially reflected by enhanced D-dimer levels. Poor vascular health, which is associated with the cardiometabolic health conditions frequently reported in people with severer forms of COVID-19, might exacerbate the risk of coagulopathy and mortality. Sedentary lifestyles might also contribute to the development of coagulopathy, and physical activity participation has been inherently lowered due to at-home regulations established to slow the spread of this highly infectious disease. It is possible that COVID-19, coagulation, and reduced physical activity may contribute to generate a "perfect storm," where each fuels the other and potentially increases mortality risk. Several pharmaceutical agents are being explored to treat COVID-19, but potential negative consequences are associated with their use. Exercise is known to mitigate many of the identified side effects from the pharmaceutical agents being trialled but has not yet been considered as part of management for COVID-19. From the limited available evidence in people with cardiometabolic health conditions, low- to moderate-intensity exercise might have the potential to positively influence biochemical markers of coagulopathy, whereas high-intensity exercise is likely to increase thrombotic risk. Therefore, low- to moderate-intensity exercise could be an adjuvant therapy for people with mild-to-moderate COVID-19 and reduce the risk of developing severe symptoms of illness that are associated with enhanced mortality.


Assuntos
Coagulação Sanguínea , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Exercício Físico , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Anticoagulantes/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Infecções por Coronavirus/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinólise , Hemostasia , Humanos , Inflamação , Pandemias , Pneumonia Viral/complicações , Risco , Trombose/sangue , Trombose/complicações
8.
BMC Pregnancy Childbirth ; 20(1): 511, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887569

RESUMO

BACKGROUND: It has been proposed that pregnant women and their fetuses may be particularly at risk for poor outcomes due to the coronavirus (COVID-19) pandemic. From the few case series that are available in the literature, women with high risk pregnancies have been associated with higher morbidity. It has been suggested that pregnancy induced immune responses and cardio-vascular changes can exaggerate the course of the COVID-19 infection. CASE PRESENTATION: A 26-year old Somalian woman (G2P1) presented with a nine-day history of shortness of breath, dry cough, myalgia, nausea, abdominal pain and fever. A nasopharyngeal swab returned positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Her condition rapidly worsened leading to severe liver and coagulation impairment. An emergency Caesarean section was performed at gestational week 32 + 6 after which the patient made a rapid recovery. Severe COVID-19 promptly improved by the termination of the pregnancy or atypical HELLP (Hemolysis, Elevated Liver Enzymes and Low Platelet Count) exacerbated by concomitant COVID-19 infection could not be ruled out. There was no evidence of vertical transmission. CONCLUSIONS: This case adds to the growing body of evidence which raises concerns about the possible negative maternal outcomes of COVID-19 infection during pregnancy and advocates for pregnant women to be recognized as a vulnerable group during the current pandemic.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Cesárea , Infecções por Coronavirus/sangue , Hepatopatias/sangue , Obesidade Materna , Pneumonia Viral/sangue , Complicações Infecciosas na Gravidez/sangue , Adulto , Antitrombina III/metabolismo , Índice de Apgar , Betacoronavirus , Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/fisiopatologia , Diagnóstico Diferencial , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Síndrome HELLP/diagnóstico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , L-Lactato Desidrogenase/sangue , Hepatopatias/etiologia , Pulmão/diagnóstico por imagem , Masculino , Pandemias , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/fisiopatologia , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , Suécia , Tomografia Computadorizada por Raios X
9.
J Int Med Res ; 48(9): 300060520955037, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32960106

RESUMO

BACKGROUND: The roles of inflammation and hypercoagulation in predicting outcomes of coronavirus disease 2019 (COVID-19) are unclear. METHODS: Adult patients diagnosed with COVID-19 from 28 January 2020 to 4 March 2020 in Tongji Hospital, Wuhan were recruited. Data on related parameters were collected. Univariate analysis and multivariable binary logistic regression were used to explore predictors of critical illness and mortality. RESULTS: In total, 199 and 44 patients were enrolled in the training and testing sets, respectively. Elevated ferritin, tumor necrosis factor-α and D-dimer and decreased albumin concentration were associated with disease severity. Older age, elevated ferritin and elevated interleukin-6 were associated with 28-day mortality. The FAD-85 score, defined as age + 0.01 * ferritin +D-dimer, was used to predict risk of mortality. The sensitivity, specificity and accuracy of FAD-85 were 86.4%, 81.8% and 86.4%, respectively. A nomogram was established using age, ferritin and D-dimer to predict the risk of 28-day mortality. CONCLUSIONS: Thrombo-inflammatory parameters provide key information on the severity and prognosis of COVID-19 and can be used as references for clinical treatment to correct inflammatory and coagulation abnormalities.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Coagulação Intravascular Disseminada/mortalidade , Pneumonia Viral/mortalidade , Trombose/mortalidade , Adulto , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/virologia , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Interleucina-6/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Prognóstico , Projetos de Pesquisa , Estudos Retrospectivos , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , Análise de Sobrevida , Trombose/complicações , Trombose/diagnóstico , Trombose/virologia , Fator de Necrose Tumoral alfa/sangue
10.
Epidemiol Infect ; 148: e202, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32892787

RESUMO

D-dimer level on admission is a promising biomarker to predict mortality in patients with COVID-19. In this study, we reviewed the association between on-admission D-dimer levels and all-cause mortality risk in COVID-19 patients. Peer-reviewed studies and preprints reporting categorised D-dimer levels on admission and all-cause mortality until 24 May 2020 were searched for using the following keywords: 'COVID-19', 'D-dimer' and 'Mortality'. A meta-analysis was performed to determine the pooled risk ratio (RR) for all-cause mortality. In total, 2911 COVID-19 patients from nine studies were included in this meta-analysis. Regardless of the different D-dimer cut-off values used, the pooled RR for all-cause mortality in patients with elevated vs. normal on-admission D-dimer level was 4.77 (95% confidence interval (CI) 3.02-7.54). Sensitivity analysis did not significantly affect the overall mortality risk. Analysis restricted to studies with 0.5 µg/ml as the cut-off value resulted in a pooled RR for mortality of 4.60 (95% CI 2.72-7.79). Subgroup analysis showed that the pooled all-cause mortality risk was higher in Chinese vs. non-Chinese studies (RR 5.87; 95% CI 2.67-12.89 and RR 3.35; 95% CI 1.66-6.73; P = 0.29). On-admission D-dimer levels showed a promising prognostic role in predicting all-cause mortality in COVID-19 patients, elevated D-dimer levels were associated with increased risk of mortality.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Biomarcadores , Humanos , Pandemias
11.
Trials ; 21(1): 769, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895056

RESUMO

OBJECTIVES: To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. TRIAL DESIGN: This is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization. EXCLUSION CRITERIA: pregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent. INTERVENTION AND COMPARATOR: The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: As a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio. RANDOMISATION: After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. BLINDING (MASKING): Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group). TRIAL STATUS: The local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28th June and is expected to end in November 2020. TRIAL REGISTRATION: The protocol is registered before starting subject recruitment under the title: "Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial" in ClinicalTrials.org with the registration number: NCT04445935 . Registered on 24 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Antitrombinas/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/terapia , Anticoagulantes/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/sangue , Estado Terminal , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Hirudinas , Humanos , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/sangue , Catar , Proteínas Recombinantes/uso terapêutico
13.
Clin Imaging ; 67: 207-213, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32871424

RESUMO

PURPOSE: We describe the presenting characteristics and hospital course of 11 novel coronavirus (COVID-19) patients who developed spontaneous subcutaneous emphysema (SE) with or without pneumomediastinum (SPM) in the absence of prior mechanical ventilation. MATERIALS AND METHODS: A total of 11 non-intubated COVID-19 patients (8 male and 3 female, median age 61 years) developed SE and SPM between March 15 and April 30, 2020 at a multi-center urban health system in New York City. Demographics (age, gender, smoking status, comorbid conditions, and body-mass index), clinical variables (temperature, oxygen saturation, and symptoms), and laboratory values (white blood cell count, C-reactive protein, D-dimer, and peak interleukin-6) were collected. Chest radiography (CXR) and computed tomography (CT) were analyzed for SE, SPM, and pneumothorax by a board-certified cardiothoracic-fellowship trained radiologist. RESULTS: Eleven non-intubated patients developed SE, 36% (4/11) of whom had SE on their initial CXR. Concomitant SPM was apparent in 91% (10/11) of patients, and 45% (5/11) also developed pneumothorax. Patients developed SE on average 13.3 days (SD: 6.3) following symptom onset. No patients reported a history of smoking. The most common comorbidities included hypertension (6/11), diabetes mellitus (5/11), asthma (3/11), dyslipidemia (3/11), and renal disease (2/11). Four (36%) patients expired during hospitalization. CONCLUSION: SE and SPM were observed in a cohort of 11 non-intubated COVID-19 patients without any known cause or history of invasive ventilation. Further investigation is required to elucidate the underlying mechanism in this patient population.


Assuntos
Infecções por Coronavirus/complicações , Enfisema Mediastínico/etiologia , Pneumonia Viral/complicações , Enfisema Subcutâneo/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Comorbidade , Infecções por Coronavirus/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitalização , Humanos , Masculino , Enfisema Mediastínico/epidemiologia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Respiração Artificial/efeitos adversos , Enfisema Subcutâneo/epidemiologia , Tomografia Computadorizada por Raios X/métodos
14.
Int Heart J ; 61(5): 993-998, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921671

RESUMO

Venous thromboembolism (VTE) is a life-threatening complication after trauma. Several studies have reported VTE prophylaxis using low-molecular-weight heparin; however, there is no consensus for prophylaxis after trauma. This study aimed to assess the efficacy and safety of our new anticoagulation therapy protocol using unfractionated heparin (UFH) plus intermittent pneumatic compression (IPC) to prevent post-traumatic VTE in high-risk trauma patients.This study enrolled 70 trauma patients who were admitted to the emergency medical center of Nagasaki University Hospital and had Risk Assessment Profile (RAP) scores ≥ 5. After stopping bleeding at the trauma site, all patients received intravenous UFH (10,000 U/day) plus IPC, which was continued for 14 days or until the patients could walk. On days 7 and 14, all patients underwent lower extremity sonography for deep-vein thrombosis screening. VTE incidences between patients with the above intervention and historical controls with IPC alone were compared.No significant differences in age, sex, and the RAP score were observed between the 105 controls and intervention patients. VTE occurrence was fewer in patients with the intervention (14.3%) than in the controls (28.6%; P = 0.029). No hemorrhagic complications occurred after UFH administration. Multivariable logistic analysis revealed a significant association between the intervention and low incidence of VTE (odds ratio: 0.390; 95% confidence interval: 0.163-0.913; P = 0.030).Routine UFH administration with IPC may prevent post-traumatic VTE without adverse events.


Assuntos
Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Dispositivos de Compressão Pneumática Intermitente , Embolia Pulmonar/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/prevenção & controle , Ferimentos e Lesões/terapia , Idoso , Estudos de Coortes , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitalização , Humanos , Escala de Gravidade do Ferimento , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tempo de Tromboplastina Parcial , Medição de Risco , Trombofilia/sangue , Ferimentos e Lesões/sangue
16.
J Thromb Thrombolysis ; 50(4): 825-832, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32761495

RESUMO

The new outbreak of Coronavirus Disease 2019 (COVID-19) has emerged as a serious global public health concern. A more in-depth study of blood coagulation abnormality is needed. We retrospectively analyzed 147 consecutive patients with COVID-19 who were admitted to three ICUs in Wuhan from February 9th, 2020 to March 20th, 2020. The baseline coagulation and other characteristics were studied. Our results showed that the prolonged PT, FDP, DD were positively correlated with the levels of neutrophils, ferritin, LDH, total bilirubin, multi-inflammation cytokines, and negatively correlated with the lymphocytes level (p < 0.01). The level of ATIII was significantly negatively correlated with the levels of neutrophils, ferritin, LDH, total bilirubin, IL2R, IL6 and IL8 (p < 0.05). The patients in the ARDS group had a more prominent abnormality in PT, FDP, DD and ATIII, while the patients in the AKI group had more prolonged PT, more severe FDP and DD level, more inferior ATIII and Fib level than those in the non-AKI group (p < 0.01). The value of PT, DD and FDP were positively correlated with the classical APACHE II, SOFA and qSOFA scores, while the ATIII was negatively correlated with them (p < 0.001). The high levels of PT, FDP and DD were correlated with in-hospital mortality (p < 0.001). In conclusion, blood coagulation disorder was prominent in ICU patients with COVID-19 and was correlated with multi-inflammation factors. The abnormality of blood coagulation parameters could be an adverse prognostic indicator for ICU patients with COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Transtornos da Coagulação Sanguínea/virologia , Coagulação Sanguínea , Infecções por Coronavirus/terapia , Mediadores da Inflamação/sangue , Inflamação/virologia , Unidades de Terapia Intensiva , Pneumonia Viral/terapia , Idoso , Antitrombina III/metabolismo , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/mortalidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Mortalidade Hospitalar , Interações Hospedeiro-Patógeno , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/mortalidade , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
17.
Clin Immunol ; 219: 108555, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32771488

RESUMO

Respiratory failure and acute kidney injury (AKI) are associated with high mortality in SARS-CoV-2-associated Coronavirus disease 2019 (COVID-19). These manifestations are linked to a hypercoaguable, pro-inflammatory state with persistent, systemic complement activation. Three critical COVID-19 patients recalcitrant to multiple interventions had skin biopsies documenting deposition of the terminal complement component C5b-9, the lectin complement pathway enzyme MASP2, and C4d in microvascular endothelium. Administration of anti-C5 monoclonal antibody eculizumab led to a marked decline in D-dimers and neutrophil counts in all three cases, and normalization of liver functions and creatinine in two. One patient with severe heart failure and AKI had a complete remission. The other two individuals had partial remissions, one with resolution of his AKI but ultimately succumbing to respiratory failure, and another with a significant decline in FiO2 requirements, but persistent renal failure. In conclusion, anti-complement therapy may be beneficial in at least some patients with critical COVID-19.


Assuntos
Lesão Renal Aguda/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus/patogenicidade , Inativadores do Complemento/uso terapêutico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Lesão Renal Aguda/complicações , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/virologia , Adulto , Betacoronavirus/imunologia , Biomarcadores/metabolismo , Ativação do Complemento/efeitos dos fármacos , Complemento C4b/antagonistas & inibidores , Complemento C5/antagonistas & inibidores , Complexo de Ataque à Membrana do Sistema Complemento/antagonistas & inibidores , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Imunidade Humoral/efeitos dos fármacos , Masculino , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Serina Proteases Associadas a Proteína de Ligação a Manose/imunologia , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/patologia , Pandemias , Fragmentos de Peptídeos/antagonistas & inibidores , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia
18.
Eur J Haematol ; 105(6): 741-750, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32749010

RESUMO

BACKGROUND: Abnormal coagulation parameters have been reported in COVID-19-infected patients. Although the underlying mechanism of COVID-19 coagulopathy remains unknown, it has been suggested to be a form of disseminated intravascular coagulation (DIC). OBJECTIVES: The aim of our study was to analyze the coagulation parameters of patients with COVID-19, determine whether coagulation factors consumption occurs and identify potential prognostic biomarkers of the disease. PATIENTS/METHODS: Blood samples from hospitalized patients with COVID-19 pneumonia were collected. We performed basic coagulation tests and quantification of coagulation factors and physiological inhibitor proteins. Laboratory data were compared with clinical data and outcomes. RESULTS: The study involved 206 patients (63.6% male). D-dimer was particularly elevated (median 450 ng/mL; IQR 222.5-957.3). Free protein S levels were below the normal range (median 56.6%; IQR: 43.6-68.9), and factor VIII showed an increasing trend (median 173.4%; IQR: 144.1-214.9). However, all coagulation factors were within normal limits. We found no correlation between abnormal coagulation parameters and thrombosis, except for higher D-dimer (HR 1.99; 95% CI 1.3-3.1; P = .002). CONCLUSIONS: COVID-19 is associated with coagulopathy that correlates with poor prognosis. However, we did not demonstrate a consumption of coagulation factors, as seen in DIC.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/complicações , Coagulação Intravascular Disseminada/complicações , Fator VIII/metabolismo , Pneumonia Viral/complicações , Trombose Venosa/complicações , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Testes de Coagulação Sanguínea , Plaquetas/patologia , Plaquetas/virologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/mortalidade , Coagulação Intravascular Disseminada/virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Prognóstico , Proteína S/metabolismo , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Trombose Venosa/diagnóstico , Trombose Venosa/mortalidade , Trombose Venosa/virologia
19.
Adv Biol Regul ; 77: 100735, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32773098

RESUMO

The novel Corona virus infection (Covid-19) first identified in China in December 2019 has rapidly progressed in pandemic leading to significant mortality and unprecedented challenge for healthcare systems. Although the clinical spectrum of Covid-19 is variable, acute respiratory failure and systemic coagulopathy are common in severe Covid-19 patients. Lung is an important target of the SARS-CoV-2 virus causing eventually acute respiratory distress syndrome associated to a thromboinflammatory state. The cytokinic storm, thromboinflammation and pulmonary tropism are the bedrock of tissue lesions responsible for acute respiratory failure and for prolonged infection that may lead to multiple organ failure and death. The thrombogenicity of this infectious disease is illustrated by the high frequency of thromboembolic events observed even in Covid-19 patients treated with anticoagulation. Increased D-Dimers, a biomarker reflecting activation of hemostasis and fibrinolysis, and low platelet count (thrombocytopenia) are associated with higher mortality in Covid-19 patients. In this review, we will summarize our current knowledge on the thromboembolic manifestations, the disturbed hemostatic parameters, and the thromboinflammatory conditions associated to Covid-19 and we will discuss the modalities of anticoagulant treatment or other potential antithrombotic options.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/complicações , Coagulação Intravascular Disseminada/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Insuficiência Respiratória/complicações , Doença Aguda , Biomarcadores/sangue , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Plaquetas/virologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/virologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Interações Hospedeiro-Patógeno , Humanos , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/virologia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/virologia , Análise de Sobrevida
20.
BMC Pregnancy Childbirth ; 20(1): 481, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32838744

RESUMO

BACKGROUND: The world's understanding of COVID-19 continues to evolve as the scientific community discovers unique presentations of this disease. This case report depicts an unexpected intraoperative coagulopathy during a cesarean section in an otherwise asymptomatic patient who was later found to have COVID-19. This case suggests that there may be a higher risk for intrapartum bleeding in the pregnant, largely asymptomatic COVID-positive patient with more abnormal COVID laboratory values. CASE: The case patient displayed D-Dimer elevations beyond what is typically observed among this hospital's COVID-positive peripartum population and displayed significantly more oozing than expected intraoperatively, despite normal prothrombin time, international normalized ratio, fibrinogen, and platelets. CONCLUSION: There is little published evidence on the association between D-Dimer and coagulopathy among the pregnant population infected with SARS-CoV-2. This case report contributes to the growing body of evidence on the effects of COVID-19 in pregnancy. A clinical picture concerning for intraoperative coagulopathy may be associated with SARS-CoV-2 infection during cesarean sections, and abnormal COVID laboratory tests, particularly D-Dimer, may help identify the patients in which this presentation occurs.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Perda Sanguínea Cirúrgica , Apresentação Pélvica/cirurgia , Cesárea , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Complicações Hematológicas na Gravidez/sangue , Complicações Infecciosas na Gravidez/sangue , Adulto , Antifibrinolíticos/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/metabolismo , Proteína C-Reativa/metabolismo , Cauterização , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/metabolismo , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Hemostasia Cirúrgica , Humanos , Coeficiente Internacional Normatizado , Metilergonovina/uso terapêutico , Oligo-Hidrâmnio , Ocitócicos/uso terapêutico , Ocitocina/uso terapêutico , Pandemias , Contagem de Plaquetas , Pneumonia Viral/diagnóstico , Pneumonia Viral/metabolismo , Gravidez , Complicações Hematológicas na Gravidez/tratamento farmacológico , Complicações Hematológicas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/metabolismo , Tempo de Protrombina , Ácido Tranexâmico/uso terapêutico , Inércia Uterina/tratamento farmacológico
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