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2.
Euro Surveill ; 25(22)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32524957

RESUMO

End of April 2020, French clinicians observed an increase in cases presenting with paediatric inflammatory multisystem syndrome (PIMS). Nationwide surveillance was set up and demonstrated temporospatial association with the coronavirus disease (COVID-19) epidemic for 156 reported cases as at 17 May: 108 were classified as confirmed (n = 79), probable (n = 16) or possible (n = 13) post-COVID-19 PIMS cases. A continuum of clinical features from Kawasaki-like disease to myocarditis was observed, requiring intensive care in 67% of cases.


Assuntos
Infecções por Coronavirus/diagnóstico , Coronavirus/isolamento & purificação , Pneumonia Viral/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Betacoronavirus , Criança , Pré-Escolar , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Surtos de Doenças , Feminino , França/epidemiologia , Humanos , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Síndrome de Resposta Inflamatória Sistêmica/etiologia
3.
Endocrine ; 68(3): 471-474, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32507963

RESUMO

The novel coronavirus disease COVID-19 is produced by SARS-CoV-2. WHO has declared COVID-19 as a public health emergency, with the most susceptible populations (requiring ventilation) being the elderly, pregnant women and people with associated co-morbidities including heart failure, uncontrolled diabetes, chronic obstructive pulmonary disease, asthma and cancer. However, such general guidance does not provide information regarding COVID-19 risks in patients with suffering from pre-existing thyroid problems, and furthermore, we do not know whether patients with COVID-19 (symptomatic or without symptoms), who have not previously had thyroid issues develop endocrine thyroid dysfunction after infection. The European Society for Endocrinology recently published a statement on COVID-19 and endocrine diseases (Endocrine, 2020); however, thyroid diseases were not mentioned specifically. We have therefore reviewed the current literature on thyroid diseases (excluding cancer) and COVID-19, including data from the previous coronavirus pandemic caused by the SARS-associated coronavirus (SARS-CoV), a member of the same family Coronaviridae leading to severe acute respiratory syndrome (SARS). At the moment there are no data suggesting that thyroid patients are at higher risk of COVID-19, but this requites further research and data analysis.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Doenças da Glândula Tireoide/complicações , Infecções por Coronavirus/imunologia , Humanos , Pandemias , Pneumonia Viral/imunologia , Fatores de Risco , Vírus da SARS , Síndrome Respiratória Aguda Grave , Doenças da Glândula Tireoide/imunologia , Doenças da Glândula Tireoide/virologia , Tireoidite Autoimune/virologia
4.
Mol Med ; 26(1): 58, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546125

RESUMO

In light of the present therapeutic situation in COVID-19, any measure to improve course and outcome of seriously affected individuals is of utmost importance. We recap here evidence that supports the use of human recombinant erythropoietin (EPO) for ameliorating course and outcome of seriously ill COVID-19 patients. This brief expert review grounds on available subject-relevant literature searched until May 14, 2020, including Medline, Google Scholar, and preprint servers. We delineate in brief sections, each introduced by a summary of respective COVID-19 references, how EPO may target a number of the gravest sequelae of these patients. EPO is expected to: (1) improve respiration at several levels including lung, brainstem, spinal cord and respiratory muscles; (2) counteract overshooting inflammation caused by cytokine storm/ inflammasome; (3) act neuroprotective and neuroregenerative in brain and peripheral nervous system. Based on this accumulating experimental and clinical evidence, we finally provide the research design for a double-blind placebo-controlled randomized clinical trial including severely affected patients, which is planned to start shortly.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Eritropoetina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Fármacos do Sistema Respiratório/uso terapêutico , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/imunologia , Tronco Encefálico/virologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Método Duplo-Cego , Humanos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/virologia , Pandemias , Nervo Frênico/efeitos dos fármacos , Nervo Frênico/imunologia , Nervo Frênico/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Estudo de Prova de Conceito , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/uso terapêutico , Músculos Respiratórios/efeitos dos fármacos , Músculos Respiratórios/imunologia , Músculos Respiratórios/virologia , Índice de Gravidade de Doença , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/virologia
5.
BMJ Glob Health ; 5(6)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32565430

RESUMO

The evidence produced in mathematical models plays a key role in shaping policy decisions in pandemics. A key question is therefore how well pandemic models relate to their implementation contexts. Drawing on the cases of Ebola and influenza, we map how sociological and anthropological research contributes in the modelling of pandemics to consider lessons for COVID-19. We show how models detach from their implementation contexts through their connections with global narratives of pandemic response, and how sociological and anthropological research can help to locate models differently. This potentiates multiple models of pandemic response attuned to their emerging situations in an iterative and adaptive science. We propose a more open approach to the modelling of pandemics which envisages the model as an intervention of deliberation in situations of evolving uncertainty. This challenges the 'business-as-usual' of evidence-based approaches in global health by accentuating all science, within and beyond pandemics, as 'emergent' and 'adaptive'.


Assuntos
Controle de Doenças Transmissíveis , Infecções por Coronavirus/epidemiologia , Política de Saúde , Modelos Biológicos , Pneumonia Viral/epidemiologia , Viroses/epidemiologia , Infecções por Coronavirus/imunologia , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/imunologia , Humanos , Imunidade Coletiva , Vírus da Influenza A Subtipo H1N1/fisiologia , Virus da Influenza A Subtipo H5N1/fisiologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Pandemias , Pneumonia Viral/imunologia , Incerteza
8.
Signal Transduct Target Ther ; 5(1): 89, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32533062

RESUMO

Coronavirus infections of multiple origins have spread to date worldwide, causing severe respiratory diseases. Seven coronaviruses that infect humans have been identified: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. Among them, SARS-CoV and MERS-CoV caused outbreaks in 2002 and 2012, respectively. SARS-CoV-2 (COVID-19) is the most recently discovered. It has created a severe worldwide outbreak beginning in late 2019, leading to date to over 4 million cases globally. Viruses are genetically simple, yet highly diverse. However, the recent outbreaks of SARS-CoV and MERS-CoV, and the ongoing outbreak of SARS-CoV-2, indicate that there remains a long way to go to identify and develop specific therapeutic treatments. Only after gaining a better understanding of their pathogenic mechanisms can we minimize viral pandemics. This paper mainly focuses on SARS-CoV, MERS-CoV, and SARS-CoV-2. Here, recent studies are summarized and reviewed, with a focus on virus-host interactions, vaccine-based and drug-targeted therapies, and the development of new approaches for clinical diagnosis and treatment.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Pandemias , Pneumonia Viral/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Betacoronavirus/genética , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Terapia de Alvo Molecular/métodos , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/genética , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/virologia
9.
JCO Glob Oncol ; 6: 844-851, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32552110

RESUMO

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has imposed a unique challenge to oncology patients and their treatment. There is no study related to the patients' preference for systemic therapy during this pandemic. We have conducted a prospective study to analyze that aspect. METHODS: All consecutive patients who visited during the lockdown period from April 1-10, 2020, for systemic chemotherapy were included in the study for a questionnaire-based survey to evaluate the willingness to continue chemotherapy during this pandemic and factors influencing the decisions. RESULTS: A total of 302 patients were included (median age, 56 years; range, 21-77 years). Most common sites of cancer were breast (n = 114), lung (n = 44), ovary (n = 34), and colon (n = 20). Home address was within the city for 125 patients (42%), outside the city for 138 (46%), and outside the state for 37 (12%). Treatment was curative in 150 patients and palliative in 152. Educational status was primary and above for 231 patients and no formal schooling for 71. A total of 203 patients wanted to continue chemotherapy, 40 wanted to defer, and 56 wanted the physician to decide. Knowledge about COVID-19 strongly correlated with intent of treatment (P = .01), disease status (P = .02), knowledge about immunosuppression (P < .001), home location (P = .02), and education status (P = .003). The worry about catching SARS-CoV-2 was high in those with controlled disease (P = .06) and knowledge about immunosuppression (P = .02). Worry about disease progression was more with palliative intent (P < .001). CONCLUSION: This study shows that oncology patients in our country are more worried about disease progression than the SARS-CoV-2 and wish to continue chemotherapy during this pandemic. The treatment guidelines in the COVID-19 scenario should incorporate patients' perspectives.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Imunoterapia/normas , Neoplasias/terapia , Cuidados Paliativos/normas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Progressão da Doença , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/psicologia , Cuidados Paliativos/psicologia , Cuidados Paliativos/estatística & dados numéricos , Preferência do Paciente/psicologia , Preferência do Paciente/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Inquéritos e Questionários/estatística & dados numéricos , Adulto Jovem
10.
Signal Transduct Target Ther ; 5(1): 100, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561706
11.
Elife ; 92020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32573433

RESUMO

We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID-19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients, monoclonal antibodies against the viral S-protein, and soluble forms of the receptor for the virus, angiotensin converting enzyme 2. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Imunização Passiva , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Anticorpos Monoclonais , Anticorpos Antivirais , Betacoronavirus/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , Humanos , Pandemias , Vírus da SARS/imunologia , Glicoproteína da Espícula de Coronavírus/química
13.
BMJ ; 369: m2094, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493739

RESUMO

OBJECTIVES: To describe the characteristics of children and adolescents affected by an outbreak of Kawasaki-like multisystem inflammatory syndrome and to evaluate a potential temporal association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: General paediatric department of a university hospital in Paris, France. PARTICIPANTS: 21 children and adolescents (aged ≤18 years) with features of Kawasaki disease who were admitted to hospital between 27 April and 11 May 2020 and followed up until discharge by 15 May 2020. MAIN OUTCOME MEASURES: The primary outcomes were clinical and biological data, imaging and echocardiographic findings, treatment, and outcomes. Nasopharyngeal swabs were prospectively tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) and blood samples were tested for IgG antibodies to the virus. RESULTS: 21 children and adolescents (median age 7.9 (range 3.7-16.6) years) were admitted with features of Kawasaki disease over a 15 day period, with 12 (57%) of African ancestry. 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms during the early stage of illness and high levels of inflammatory markers. 19 (90%) had evidence of recent SARS-CoV-2 infection (positive RT-PCR result in 8/21, positive IgG antibody detection in 19/21). All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients. Moderate coronary artery dilations were detected in 5 (24%) of the patients during hospital stay. By 15 May 2020, after 8 (5-17) days of hospital stay, all patients were discharged home. CONCLUSIONS: The ongoing outbreak of Kawasaki-like multisystem inflammatory syndrome among children and adolescents in the Paris area might be related to SARS-CoV-2. In this study an unusually high proportion of the affected children and adolescents had gastrointestinal symptoms, Kawasaki disease shock syndrome, and were of African ancestry.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Adolescente , Corticosteroides/uso terapêutico , Betacoronavirus/genética , Betacoronavirus/imunologia , Criança , Pré-Escolar , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Nasofaringe/virologia , Pandemias , Paris , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Estudos Prospectivos , RNA Viral/genética , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/etiologia
14.
Ann Hematol ; 99(7): 1421-1428, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32495027

RESUMO

Coronavirus disease 2019 (COVID-19) is a new human infectious disease. The etiology for this outbreak is a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus far, related research on COVID-19 is still in preliminary stage. This paper summarized the latest outcomes of corresponding study from Chinese centers and clarified the hematopoietic abnormality caused by SARS-CoV-2 and potential mechanism. Lymphopenia was common in the early stage after the onset of COVID-19. A significant decrease was observed in peripheral CD4+ and CD8+ T lymphocytes. As the illness progressed, neutrophilia emerged in several cases, and patients with severe critical pulmonary conditions showed higher neutrophils than common type. Thrombocytopenia was resulting from the consumption and/or the reduced production of platelets in damaged lungs. Anemia was not observed notably, but the decrease in hemoglobin was frequent. The activation of monocyte-macrophage system aggravates the immune damage of lung and other tissues, which leads to the increase of D-dimer, prothrombin time, and platelet consumption.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Progressão da Doença , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , China , Infecções por Coronavirus/patologia , Feminino , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Pulmão/imunologia , Pulmão/patologia , Linfopenia/virologia , Masculino , Neutrófilos , Pandemias , Pneumonia Viral/patologia , Trombocitopenia/virologia
15.
ACS Nano ; 14(6): 6383-6406, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32519842

RESUMO

The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of "nanoimmunity by design" can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Betacoronavirus/genética , Betacoronavirus/imunologia , Biomimética , Simulação por Computador , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Desinfecção , Sistemas de Liberação de Medicamentos , Microbiologia Ambiental , Humanos , Imunomodulação , Máscaras , Nanomedicina , Nanotecnologia/tendências , Pandemias/prevenção & controle , Equipamento de Proteção Individual , Fotoquimioterapia , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Vacinas Virais/genética , Vacinas Virais/farmacologia
16.
Nutrients ; 12(6)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32532069

RESUMO

Infection caused by the SARS-CoV-2 coronavirus worldwide has led the World Health Organization to declare a COVID-19 pandemic. Because there is no cure or treatment for this virus, it is emergingly urgent to find effective and validated methods to prevent and treat COVID-19 infection. In this context, alternatives related to nutritional therapy might help to control the infection. This narrative review proposes the importance and role of probiotics and diet as adjunct alternatives among the therapies available for the treatment of this new coronavirus. This review discusses the relationship between intestinal purine metabolism and the use of Lactobacillus gasseri and low-purine diets, particularly in individuals with hyperuricemia, as adjuvant nutritional therapies to improve the immune system and weaken viral replication, assisting in the treatment of COVID-19. These might be promising alternatives, in addition to many others that involve adequate intake of vitamins, minerals and bioactive compounds from food.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/terapia , Dieta/métodos , Imunomodulação/fisiologia , Pneumonia Viral/terapia , Probióticos/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/microbiologia , Humanos , Lactobacillus gasseri/imunologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/microbiologia , Purinas/imunologia , Purinas/metabolismo , Replicação Viral/imunologia
18.
MMWR Morb Mortal Wkly Rep ; 69(23): 714-721, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32525850

RESUMO

Compared with the volume of data on coronavirus disease 2019 (COVID-19) outbreaks among older adults, relatively few data are available concerning COVID-19 in younger, healthy persons in the United States (1,2). In late March 2020, the aircraft carrier USS Theodore Roosevelt arrived at port in Guam after numerous U.S. service members onboard developed COVID-19. In April, the U.S. Navy and CDC investigated this outbreak, and the demographic, epidemiologic, and laboratory findings among a convenience sample of 382 service members serving aboard the aircraft carrier are reported in this study. The outbreak was characterized by widespread transmission with relatively mild symptoms and asymptomatic infection among this sample of mostly young, healthy adults with close, congregate exposures. Service members who reported taking preventive measures had a lower infection rate than did those who did not report taking these measures (e.g., wearing a face covering, 55.8% versus 80.8%; avoiding common areas, 53.8% versus 67.5%; and observing social distancing, 54.7% versus 70.0%, respectively). The presence of neutralizing antibodies, which represent antibodies that inhibit SARS-CoV-2, among the majority (59.2%) of those with antibody responses is a promising indicator of at least short-term immunity. This report improves the understanding of COVID-19 in the U.S. military and among young adults in congregate settings and reinforces the importance of preventive measures to lower risk for infection in similar environments.


Assuntos
Aeronaves , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Surtos de Doenças , Militares/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pandemias , Estados Unidos/epidemiologia , Adulto Jovem
19.
Trials ; 21(1): 468, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493441

RESUMO

OBJECTIVES: The purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6, IL-6 receptor and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome. TRIAL DESIGN: A phase 3 prospective, multi-center, interventional, open label, 6-arm 2x2 factorial design study. PARTICIPANTS: Subjects will be recruited at the specialized COVID-19 wards and/or ICUs at 16 Belgian participating hospitals. Only adult (≥18y old) patients will be recruited with recent (≤16 days) COVID-19 infection and acute hypoxia (defined as PaO2/FiO2 below 350mmHg or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation) and signs of systemic cytokine release syndrome characterized by high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those, who have not been on mechanical ventilation for more than 24 hours before randomisation. Patients should have had a chest X-ray and/or CT scan showing bilateral infiltrates within the last 2 days before randomisation. Patients with active bacterial or fungal infection will be excluded. INTERVENTION AND COMPARATOR: Patients will be randomized to 1 of 5 experimental arms versus usual care. The experimental arms consist of Anakinra alone (anti-IL-1 binding the IL-1 receptor), Siltuximab alone (anti-IL-6 chimeric antibody), a combination of Siltuximab and Anakinra, Tocilizumab alone (humanised anti-IL-6 receptor antibody) or a combination of Anakinra with Tocilizumab in addition to standard care. Patients treated with Anakinra will receive a daily subcutaneous injection of 100mg for a maximum of 28 days or until hospital discharge, whichever comes first. Siltuximab (11mg/kg) or Tocilizumab (8mg/kg, with a maximum dose of 800mg) are administered as a single intravenous injection immediately after randomization. MAIN OUTCOMES: The primary end point is the time to clinical improvement defined as the time from randomization to either an improvement of two points on a six-category ordinal scale measured daily till day 28 or discharge from the hospital or death. This ordinal scale is composed of (1) Death; (2) Hospitalized, on invasive mechanical ventilation or ECMO; (3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; (4) Hospitalized, requiring supplemental oxygen; (5) Hospitalized, not requiring supplemental oxygen; (6) Not hospitalized. RANDOMISATION: Patients will be randomized using an Interactive Web Response System (REDCap). A 2x2 factorial design was selected with a 2:1 randomization regarding the IL-1 blockade (Anakinra) and a 1:2 randomization regarding the IL-6 blockade (Siltuximab and Tocilizumab). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 342 participants will be enrolled: 76 patients will receive usual care, 76 patients will receive Siltuximab alone, 76 patients will receive Tocilizumab alone, 38 will receive Anakinra alone, 38 patients will receive Anakinra and Siltuximab and 38 patients will receive Anakinra and Tocilizumab. TRIAL STATUS: COV-AID protocol version 3.0 (15 Apr 2020). Participant recruitment is ongoing and started on April 4th 2020. Given the current decline of the COVID-19 pandemic in Belgium, it is difficult to anticipate the rate of participant recruitment. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 1st, 2020 (ClinicalTrials.gov Identifier: NCT04330638) and on EudraCT on April 3rd 2020 (Identifier: 2020-001500-41). 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
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Bélgica , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Interações Hospedeiro-Patógeno , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Interleucina-1/antagonistas & inibidores , Interleucina-1/sangue , Interleucina-1/imunologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Interleucina-6/imunologia , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Interleucina-6/antagonistas & inibidores , Receptores de Interleucina-6/sangue , Receptores de Interleucina-6/imunologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
20.
In Vivo ; 34(3 Suppl): 1567-1588, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503814

RESUMO

BACKGROUND: On March 11, 2020, the World Health Organization (WHO) declared the outbreak of coronavirus disease (COVID-19) a pandemic. Since then, thousands of people have suffered and died, making the need for a treatment of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) more crucial than ever. MATERIALS AND METHODS: The authors carried out a search in PubMed, ClinicalTrials.gov and New England Journal of Medicine (NEJM) for COVID-19 to provide information on the most promising treatments against SARS-CoV-2. RESULTS: Possible COVID-19 agents with promising efficacy and favorable safety profile were identified. The results support the combination of copper, N-acetylcysteine (NAC), colchicine and nitric oxide (NO) with candidate antiviral agents, remdesivir or EIDD-2801, as a treatment for patients positive for SARS-CoV-2. CONCLUSION: The authors propose to study the effects of the combination of copper, NAC, colchicine, NO and currently used experimental antiviral agents, remdesivir or EIDD-2801, as a potential treatment scheme for SARS-COV-2.


Assuntos
Acetilcisteína/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Colchicina/uso terapêutico , Cobre/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Óxido Nítrico/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ribonucleosídeos/uso terapêutico , Acetilcisteína/administração & dosagem , Acetilcisteína/farmacologia , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Alanina/administração & dosagem , Alanina/farmacologia , Alanina/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Antivirais/administração & dosagem , Antivirais/farmacologia , Autofagia/efeitos dos fármacos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Colchicina/administração & dosagem , Colchicina/farmacologia , Cobre/administração & dosagem , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Inflamação , Óxido Nítrico/administração & dosagem , Óxido Nítrico/farmacologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Pró-Fármacos/administração & dosagem , Pró-Fármacos/uso terapêutico , Ribonucleosídeos/administração & dosagem , Ribonucleosídeos/farmacologia , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
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