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1.
Radiographics ; 40(6): 1574-1599, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33001783

RESUMO

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in coronavirus disease 2019 (COVID-19), which was declared an official pandemic by the World Health Organization on March 11, 2020. The infection has been reported in most countries around the world. As of August 2020, there have been over 21 million cases of COVID-19 reported worldwide, with over 800 000 COVID-19-associated deaths. It has become apparent that although COVID-19 predominantly affects the respiratory system, many other organ systems can also be involved. Imaging plays an essential role in the diagnosis of all manifestations of the disease, as well as its related complications, and proper utilization and interpretation of imaging examinations is crucial. With the growing global COVID-19 outbreak, a comprehensive understanding of the diagnostic imaging hallmarks, imaging features, multisystemic involvement, and evolution of imaging findings is essential for effective patient management and treatment. To date, only a few articles have been published that comprehensively describe the multisystemic imaging manifestations of COVID-19. The authors provide an inclusive system-by-system image-based review of this life-threatening and rapidly spreading infection. In part 1 of this article, the authors discuss general aspects of the disease, with an emphasis on virology, the pathophysiology of the virus, and clinical presentation of the disease. The key imaging features of the varied pathologic manifestations of this infection that involve the pulmonary and peripheral and central vascular systems are also described. Part 2 will focus on key imaging features of COVID-19 that involve the cardiac, neurologic, abdominal, dermatologic and ocular, and musculoskeletal systems, as well as pediatric and pregnancy-related manifestations of the virus. Vascular complications pertinent to each system will be also be discussed in part 2. Online supplemental material is available for this article. ©RSNA, 2020.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pandemias , Pneumonia Viral/diagnóstico por imagem , Tromboembolia/diagnóstico por imagem , Trombose/diagnóstico por imagem , Angiografia/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Progressão da Doença , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Inflamação , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Artéria Pulmonar/diagnóstico por imagem , Receptores Virais/fisiologia , Síndrome do Desconforto Respiratório do Adulto/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/etiologia , Avaliação de Sintomas , Tromboembolia/sangue , Tromboembolia/etiologia , Trombose/sangue , Trombose/etiologia , Microangiopatias Trombóticas/diagnóstico por imagem , Microangiopatias Trombóticas/etiologia , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodos
2.
Cells ; 9(10)2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998369

RESUMO

The vitamin K-dependent factors protein S (PROS1) and growth-arrest-specific gene 6 (GAS6) and their tyrosine kinase receptors TYRO3, AXL, and MERTK, the TAM subfamily of receptor tyrosine kinases (RTK), are key regulators of inflammation and vascular response to damage. TAM signaling, which has largely studied in the immune system and in cancer, has been involved in coagulation-related pathologies. Because of these established biological functions, the GAS6-PROS1/TAM system is postulated to play an important role in SARS-CoV-2 infection and progression complications. The participation of the TAM system in vascular function and pathology has been previously reported. However, in the context of COVID-19, the role of TAMs could provide new clues in virus-host interplay with important consequences in the way that we understand this pathology. From the viral mimicry used by SARS-CoV-2 to infect cells, to the immunothrombosis that is associated with respiratory failure in COVID-19 patients, TAM signaling seems to be involved at different stages of the disease. TAM targeting is becoming an interesting biomedical strategy, which is useful for COVID-19 treatment now, but also for other viral and inflammatory diseases in the future.


Assuntos
Infecções por Coronavirus/complicações , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Pneumonia Viral/complicações , Proteína S/metabolismo , Trombose/etiologia , Imunidade Adaptativa , Animais , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Hemostasia , Humanos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Trombose/sangue , Trombose/imunologia , c-Mer Tirosina Quinase/metabolismo
3.
PLoS One ; 15(10): e0237843, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031385

RESUMO

OJECTIVES: Thrombotic and antifibrinolytic influence of Diabetes mellitus type 1 (T1DM) on haemostasis have been well demonstrated. There has been no research assessing the influence of poor glycemic control on thrombus formation under flow conditions in vitro or in pregnant type 1 diabetic women to date. PATIENTS/METHODS: This study compared singleton pregnant T1DM women (n = 21) and control pregnant subjects without any metabolic disease (n = 15). The T1DM group was divided into two subgroups of sufficient (SGC-DM; HbA1c ≤6,5%,n = 15) and poor glycaemic control (PGC-DM; HbA1c >6,5%,n = 6). Evaluation of the whole blood thrombogenicity we assessed using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan). RESULTS: Blood clot formation initiation time (T10) was significantly shortened in PGC-DM subgroup when compared to SGC-DM subgroup (p = 0,03). The area under the curve (AUC30) of blood clot time formation and the MPV (mean platelet volume) values were substantially higher in the PGC-DM subgroup in comparison to the SGC-DM group (p = 0,03). Negative correlations were noted between HbA1c and T10 values (p = 0,02) and between T10 and MPV values in the T1DM group (p = 0,04). CONCLUSIONS: Poor glycaemic control in T1DM subjects triggers a shift towards a prothrombotic and antifibrinolytic state. This phenomenon can be detected using the novel system for quantitative assessment of the platelet thrombus formation process under flow conditions in vitro. The alteration of T-TAS values in PGC-DM subgroup proves that a poor glycemic control-related shift of the equilibrium toward thrombogenesis occurs in this group of patients. Our findings need a further elucidation in research on more massive data sets to be confirmed.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Gravidez em Diabéticas/sangue , Adulto , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Feminino , Fibrinólise , Humanos , Polônia , Gravidez , Trombose/sangue , Trombose/etiologia , Adulto Jovem
4.
Open Heart ; 7(2)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32938758

RESUMO

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.


Assuntos
Infecções por Coronavirus/terapia , Dieta com Restrição de Carboidratos , Suplementos Nutricionais , Hiperinsulinismo/terapia , Insulina/sangue , Magnésio/uso terapêutico , Pneumonia Viral/terapia , Trombose/terapia , Vitamina D/uso terapêutico , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Glicemia/metabolismo , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Suplementos Nutricionais/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/epidemiologia , Cetonas/sangue , Magnésio/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Fatores de Risco , Trombose/sangue , Trombose/epidemiologia , Trombose/virologia , Vitamina D/sangue , Zinco/uso terapêutico
5.
Trials ; 21(1): 770, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907635

RESUMO

OBJECTIVES: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. TRIAL DESIGN: The OVID study is conducted as a multicentre open-label superiority randomised controlled trial. PARTICIPANTS: Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study's background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis: a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke, b. previous VTE, c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin <8 g/dL and platelet count <50 x 109 cells/L confirmed by recent laboratory test (<90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals. INTERVENTION AND COMPARATOR: Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation. MAIN OUTCOMES: Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization. SECONDARY OUTCOMES: (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment. RANDOMISATION: Patients will undergo block stratified randomization (by age: 50-70 vs. >70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24). BLINDING (MASKING): In this open-label study, no blinding procedures will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation is based on the parameters α = 0.05 (2-sided), power: 1-ß = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group. TRIAL STATUS: Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). 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
Anticoagulantes/administração & dosagem , Betacoronavirus/patogenicidade , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Enoxaparina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Enoxaparina/efeitos adversos , Estudos de Equivalência como Asunto , Interações Hospedeiro-Patógeno , Humanos , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Trombose/sangue , Trombose/diagnóstico , Trombose/virologia , Fatores de Tempo , Resultado do Tratamento
8.
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
10.
J Am Heart Assoc ; 9(21): e017773, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-32972320

RESUMO

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID-19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID-19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D-dimer, fibrinogen, or CRP (C-reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID-19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID-19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID-19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.


Assuntos
Síndrome Antifosfolipídica/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Deficiência de Proteína S/epidemiologia , Trombose/epidemiologia , Idoso , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Prevalência , Prognóstico , Proteína S/análise , Deficiência de Proteína S/sangue , Deficiência de Proteína S/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Trombose/sangue , Trombose/diagnóstico
12.
Redox Biol ; 36: 101655, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32738789

RESUMO

Nox2 is responsible for artery dysfunction via production of reactive oxidant species. RNA viruses may activate Nox2, but it is unknown if this occurs in coronavirus 2019(Covid-19). Nox2 activation by soluble Nox2-derived peptide(sNox2-dp) was measured in patients hospitalized for Covid-19 (n = 182) and controls (n = 91). sNox2-dp values were higher in Covid-19 patients versus controls and in severe versus non severe Covid-19. Patients with thrombotic events(n = 35,19%) had higher sNox2-dp than thrombotic event-free ones. A logistic regression analysis showed that sNox2 and coronary heart disease predicted thrombotic events. Oxidative stress by Nox2 activation is associated severe disease and thrombotic events in Covid-19 patients.


Assuntos
Infecções por Coronavirus/metabolismo , NADPH Oxidase 2/metabolismo , Pneumonia Viral/metabolismo , Trombose/sangue , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Oxidase 2/química , Estresse Oxidativo , Pandemias , Fragmentos de Peptídeos/sangue , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Trombose/etiologia
15.
J Thromb Thrombolysis ; 50(4): 790-794, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32789730

RESUMO

Several autopsy studies showed microthrombi in pulmonary circulation of severe COVID-19 patients. The major limitation of these investigations is that the autopsy provided static information. Some of these alterations could be secondary to the disseminated intravascular coagulation (DIC) observed as the final standard route to the multisystem organ failure exhibited in critically ill patients. We report preliminary results of an in vivo evaluation of sublingual microcirculation in thirteen patients with severe COVID-19 requiring mechanical ventilation. We observed multiple filling defects moving within the microvessels indicative of thrombi in most of the cases 11/13 (85%). This is the first imaging documentation of microvascular thrombosis in living severe COVID-19 patients since the beginning of the hospitalization. The clinical relevance of microvascular thrombosis in this disease requires further research.


Assuntos
Coagulação Sanguínea , Infecções por Coronavirus/complicações , Microcirculação , Soalho Bucal/irrigação sanguínea , Pneumonia Viral/complicações , Trombose/fisiopatologia , Idoso , Betacoronavirus/patogenicidade , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Fluxo Sanguíneo Regional , Respiração Artificial , Índice de Gravidade de Doença , Trombose/sangue , Trombose/diagnóstico por imagem , Trombose/virologia
16.
Med Clin (Barc) ; 155(8): 340-343, 2020 10 23.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32814635

RESUMO

BACKGROUND: SARS-CoV-2 infection is clinically very heterogeneous, varying from asymptomatic to severe clinical conditions with a fatal outcome. Some studies suggests that the ABO blood group could be a biological marker of susceptibility for the development of the disease. PATIENTS AND METHODS: We collected data from patients admitted with COVID-19 infection who had ABO blood group recorded, and analyzed the incidence by groups, compared with the global population in Navarre, as well as their main complications and evolution. RESULTS: Group O was proportionally less represented in the hospitalized patients with respect to the global population, although the difference was not statistically significant. Group B had significantly higher rates of thrombotic complications and required more admissions in intensive care units. CONCLUSION: The study suggests a lower susceptibility to infection in group O and a higher risk of complications in group B. Studies with a larger sample size are required in order to obtain significant results.


Assuntos
Sistema ABO de Grupos Sanguíneos , Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Trombose/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Estudos Retrospectivos , Fatores de Risco , Trombose/sangue , Trombose/diagnóstico
18.
J Clin Invest ; 130(11): 6151-6157, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32759504

RESUMO

Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyperinflammation and thrombotic microangiopathy, thereby increasing coronavirus 2019 (COVID-19) mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, and NET/human aortic endothelial cell (HAEC) cocultures. Increased plasma levels of NETs, tissue factor (TF) activity, and sC5b-9 were detected in patients. Neutrophils of patients yielded high TF expression and released NETs carrying active TF. Treatment of control neutrophils with COVID-19 platelet-rich plasma generated TF-bearing NETs that induced thrombotic activity of HAECs. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. COVID-19 serum induced complement activation in vitro, consistent with high complement activity in clinical samples. Complement C3 inhibition with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis for a pivotal role of complement and NETs in COVID-19 immunothrombosis. This study supports strategies against severe acute respiratory syndrome coronavirus 2 that exploit complement or NETosis inhibition.


Assuntos
Betacoronavirus , Complexo de Ataque à Membrana do Sistema Complemento , Infecções por Coronavirus , Armadilhas Extracelulares , Neutrófilos , Pandemias , Pneumonia Viral , Tromboplastina , Trombose , Idoso , Betacoronavirus/imunologia , Betacoronavirus/metabolismo , Ativação do Complemento/efeitos dos fármacos , Complexo de Ataque à Membrana do Sistema Complemento/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/metabolismo , Peptídeos Cíclicos/farmacologia , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Receptor da Anafilatoxina C5a/antagonistas & inibidores , Receptor da Anafilatoxina C5a/sangue , Receptor da Anafilatoxina C5a/imunologia , Síndrome do Desconforto Respiratório do Adulto/sangue , Síndrome do Desconforto Respiratório do Adulto/imunologia , Síndrome do Desconforto Respiratório do Adulto/virologia , Trombina/imunologia , Trombina/metabolismo , Tromboplastina/imunologia , Tromboplastina/metabolismo , Trombose/sangue , Trombose/imunologia , Trombose/virologia
19.
Nat Med ; 26(10): 1609-1615, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32747830

RESUMO

Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutic and public health strategies. Viral-host interactions can guide discovery of disease regulators, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of coronaviruses. To determine whether conditions associated with dysregulated complement or coagulation systems impact disease, we performed a retrospective observational study and found that history of macular degeneration (a proxy for complement-activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis and hemorrhage) are risk factors for SARS-CoV-2-associated morbidity and mortality-effects that are independent of age, sex or history of smoking. Transcriptional profiling of nasopharyngeal swabs demonstrated that in addition to type-I interferon and interleukin-6-dependent inflammatory responses, infection results in robust engagement of the complement and coagulation pathways. Finally, in a candidate-driven genetic association study of severe SARS-CoV-2 disease, we identified putative complement and coagulation-associated loci including missense, eQTL and sQTL variants of critical complement and coagulation regulators. In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to putative transcriptional genetic markers of susceptibility. The results highlight the value of using a multimodal analytical approach to reveal determinants and predictors of immunity, susceptibility and clinical outcome associated with infection.


Assuntos
Ativação do Complemento/imunologia , Infecções por Coronavirus/mortalidade , Hemorragia/epidemiologia , Degeneração Macular/epidemiologia , Pneumonia Viral/mortalidade , Trombocitopenia/epidemiologia , Trombose/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Coagulação Sanguínea/genética , Transtornos da Coagulação Sanguínea/epidemiologia , Ativação do Complemento/genética , Infecções por Coronavirus/sangue , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Expressão Gênica , Hemorragia/sangue , Hemorragia/imunologia , Doenças da Deficiência Hereditária de Complemento/epidemiologia , Doenças da Deficiência Hereditária de Complemento/imunologia , Humanos , Hipertensão/epidemiologia , Intubação Intratraqueal , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Obesidade/epidemiologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Modelos de Riscos Proporcionais , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Trombocitopenia/sangue , Trombose/sangue
20.
J Stroke Cerebrovasc Dis ; 29(9): 104891, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807409

RESUMO

PURPOSE: We summarized the clinical manifestations, laboratory data, and brain MRI of patients with Trousseau syndrome related cerebral infarction and compared them to patients with other types of cerebral infarction. Through our present research, we hope to aid the neurologists in recognizing and diagnosing this syndrome. METHODS: A total of 31 patients at our institution were identified with cerebral infarction resulting from Trousseau syndrome. We have also selected the 180 patients who have suffered from cerebral infarction as control groups and these patients were distributed to large-artery atherosclerosis group; cardio-embolism group; small-artery occlusion group, according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The clinical data and neuroimage of these patients were collected. RESULTS: All our 31 cancer patients were confirmed by pathological biopsy to be adenocarcinomas and the most common cancers are gastric and lung cancers. Patients with Trousseau syndrome exhibited high serum carbohydrate antigen CEA, CA 125 and CA 199 levels. Compared to patients with other types of cerebral infarction, patients with Trousseau syndrome had an increased severity and worse prognosis. Besides, patients had the highest mean level of plasma D-dimer. We also found multiple lesions in multiple vascular territories was the most frequent type of DWI patterns in patients of Trousseau syndrome. CONCLUSIONS: Trousseau syndrome can progress rapidly and become life-threatening. For patients who developed unexplained cerebral infarction involving multiple arterial territories, with elevated plasma D-dimer and cancer antigens, Trousseau syndrome should always be considered.


Assuntos
Adenocarcinoma/diagnóstico , Antígenos de Neoplasias/sangue , Infarto Cerebral/diagnóstico , Imagem de Difusão por Ressonância Magnética , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/complicações , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Infarto Cerebral/sangue , Infarto Cerebral/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Síndrome , Trombose/sangue , Trombose/complicações , Regulação para Cima
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