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1.
Reumatol. clín. (Barc.) ; 16(6): 437-446, nov.-dic. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194661

RESUMO

OBJETIVO: Generar las recomendaciones para la atención de pacientes con enfermedades reumáticas que reciben terapias inmunomoduladoras e inmunosupresoras (fármacos convencionales, biológicos y moléculas pequeñas) durante la pandemia por COVID-19. MATERIALES Y MÉTODOS: Las recomendaciones se realizaron utilizando el método Delphi como herramienta de acuerdo. Se conformó un panel de expertos con trayectoria académica y experiencia en investigación en reumatología. Se realizó la búsqueda de la literatura y se generó el cuestionario del ejercicio Delphi conformado por 42 preguntas. El grado de acuerdo se logró con el 80% de aprobación de los participantes. RESULTADOS: Se conformó un grupo de 11 reumatólogos de 7 ciudades del país. La tasa de respuesta fue del 100% para las 3 rondas de consulta. En la primera ronda se logró acuerdo en 35 preguntas, en la segunda ronda 37 y en la tercera ronda se logró el acuerdo de las 42 preguntas. CONCLUSIÓN: La recomendación para la mayoría de los tratamientos inmunomoduladores utilizados en reumatología es continuar con las terapias en pacientes que no tengan la infección y suspenderlas en aquellos con diagnóstico de SARS-CoV-2/COVID-19


OBJECTIVE: To produce recommendations for patients with rheumatological diseases receiving immunomodulatory and immunosuppressive therapies (conventional drugs, biologicals, and small molecules) during the COVID-19 pandemic. MATERIALS AND METHODS: The recommendations were determined using the Delphi method as an agreement tool. A panel of experts was formed, with academic backgrounds and research experience in rheumatology. A literature search was conducted and 42 questions were generated. The level of agreement was made with 80% of approval by the participants. RESULTS: A group of eleven rheumatologists from 7 cities in the country participated. The response rate was 100% for the three consultation rounds. In the first round, agreement was reached on 35 questions, on 37 in the second round, and on 42 questions in the third round. CONCLUSION: The recommendation for the majority of the pharmacological treatments used in rheumatology is to continue with immunomodulatory or immunosuppressive therapies in patients who do not have the infection, and to suspend it in patients with a diagnosis of SARS-CoV-2/COVID-19


Assuntos
Humanos , Doenças Reumáticas/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Antirreumáticos/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Doenças Reumáticas/complicações , Padrões de Prática Médica , Suspensão de Tratamento/tendências , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos
2.
Trials ; 21(1): 905, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138867

RESUMO

OBJECTIVES: The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on severe and critically ill patients with COVID-19. TRIAL DESIGN: This is a phase I/II single centre, randomised controlled, single-blinded, superiority trial, through parallel-group design with sequential assignment. Participants will be randomised either to receive both C-IVIG and standard care or only standard care (4:1). PARTICIPANTS: The study is mono-centric with the participants including COVID19 infected individuals (positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs) admitted in institute affiliated with Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan. Consenting patients above 18 years that are classified by the treating physician as severely ill i.e. showing symptoms of COVID-19 pneumonia; dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93%, PaO2/FiO2 <300, and lung infiltrates >50% on CXR; or critically ill i.e. respiratory failure, septic shock, and multiple organ dysfunction or failure. Patients with reported IgA deficiency, autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents to maintain blood pressure and patients with acute or chronic kidney injury/failure, were also excluded from the study. INTERVENTION AND COMPARATOR: The study consists of four interventions and one comparator arm. All participants receive standard hospital care which includes airway support, anti-viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti-pyretics. Randomised test patients will receive single dose of C-IVIG in following four dosage groups: Group 1: 0.15g/Kg with standard hospital care Group 2: 0.2g/Kg with standard hospital care Group 3: 0.25g/Kg with standard hospital care Group 4: 0.3g/Kg with standard hospital care Group 5 (comparator) will receive standard hospital care only MAIN OUTCOMES: The primary outcomes are assessment and follow-up of participants to observe 28-day mortality and, • the level and duration of assisted ventilation during hospital stay, • number of days to step down (shifting from ICU to isolation ward), • number of days to hospital discharge, • adverse events (Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)) during hospital stay, • change in C-Reactive Protein (CRP) levels, • change in neutrophil lymphocyte ratio to monitor inflammation. RANDOMISATION: Consenting participants who fulfill the criteria are allocated to either intervention or comparator arm with a ratio of 4:1, using sequentially numbered opaque sealed envelope simple randomization method. The participant allocated for intervention will be sequentially assigned dosage group 1-4 in ascending order. Participants will not be recruited in the next dosage group before a set number of participants in one group (10) are achieved. BLINDING (MASKING): Single blinded study, with participants blinded to allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Total 50 patients are randomised. The intervention arms consist of 40 participants divided in four groups of 10 participants while the comparator group consists of 10 patients. TRIAL STATUS: Current version of the protocol is "Version 2" dated 29th September, 2020. Participants are being recruited. Recruitment started on June, 2020 and is estimated to primarily end on January, 2021. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov, NCT04521309 on 20 August 2020 and is retrospectively registered. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).


Assuntos
Infecções por Coronavirus/terapia , Imunização Passiva/métodos , Imunoglobulinas Intravenosas , Pneumonia Viral/terapia , Adulto , Betacoronavirus/isolamento & purificação , Estado Terminal/terapia , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/efeitos adversos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Masculino , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
3.
Artigo em Inglês | MEDLINE | ID: mdl-33031994

RESUMO

As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19.


Assuntos
Ansiedade/prevenção & controle , Infecções por Coronavirus/prevenção & controle , Depressão/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Ansiedade/imunologia , Ansiedade/metabolismo , Ansiedade/virologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Citocinas/biossíntese , Citocinas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/virologia , Depressão/imunologia , Depressão/metabolismo , Depressão/virologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/virologia , Ácidos Graxos Ômega-3/imunologia , Ácidos Graxos Ômega-3/metabolismo , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/imunologia , Fatores Imunológicos/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/virologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia
4.
Urol Clin North Am ; 47(4): 413-417, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008492

RESUMO

In recent years, immunotherapy has been the focus of great interest to researchers, clinicians, and the general public. Traditionally cancer therapy has been thought to be limited to surgery, radiation therapy, or chemotherapy. Some clinicians have considered it the so-called fifth pillar of cancer therapy, following surgery, cytotoxic chemotherapy, radiation, and targeted therapy. However, the origins of immunotherapy in cancer treatment reach back at least into the nineteenth century. This article reviews the origins, development, and future of immunotherapy.


Assuntos
Fatores Imunológicos/administração & dosagem , Imunoterapia/métodos , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/terapia , História do Século XIX , Humanos , Imunoterapia/história , Estados Unidos , Neoplasias Urológicas/patologia
5.
J Interferon Cytokine Res ; 40(10): 469-471, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32881593

RESUMO

Coronavirus disease 2019 (COVID-19), which is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently emerged as a global health threat. To address this health emergency, various therapeutic approaches are currently under investigation. There is limited evidence on the effectiveness of hydroxychloroquine (HCQ) and chloroquine (CQ) as COVID-19 therapies, and thus World Health Organization (WHO) mentioned that "Current data shows that this drug does not reduce deaths among hospitalized COVID-19 patients, nor help people with mild or moderate disease." CQ and HCQ are typically used for the treatment of malaria but have been recognized for certain beneficial effects in COVID-19 patients based on some clinical outcomes from the clinical treatment of COVID-19. A standard dose of HCQ has been proven effective and less toxic than CQ in COVID-19 patients; however, a comprehensive understanding of a patient's clinical condition is necessary. Based on several hospital findings, the Food and Drug Administration (FDA) has officially cancelled the emergency use authorization for HCQ and CQ for treating hospitalized COVID-19 patients on June 15, 2020. In this review, we highlight both pros and cons of the clinical use of CQ and HCQ in COVID-19 patients.


Assuntos
Anti-Infecciosos/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Anti-Infecciosos/efeitos adversos , Azitromicina/uso terapêutico , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/patogenicidade , Cloroquina/efeitos adversos , Ensaios Clínicos como Assunto , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Sinergismo Farmacológico , Humanos , Hidroxicloroquina/efeitos adversos , Fatores Imunológicos/efeitos adversos , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Resultado do Tratamento
6.
PLoS One ; 15(9): e0238844, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32913362

RESUMO

BACKGROUND: Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of risk of bias or evaluate the certainty of the evidence. Our objective was to perform an updated review, by including new trials, any comparative observational studies, and assessing the certainty of the evidence using the GRADE framework. METHODS: We searched MEDLINE, Embase and the Cochrane Library from 2000 to November 26, 2019. Relevant websites and bibliographies of systematic reviews and guidelines were searched for studies published before 2000. Outcomes of interest were sensitization and adverse events. Risk of bias was evaluated with the Cochrane tool and ROBINS-I. The certainty of the evidence was performed using the GRADE framework. RESULTS: Thirteen randomized trials and eight comparative cohort studies were identified, evaluating 12 comparisons. Although there is some evidence of beneficial treatment effects (e.g., at 6-months postpartum, fewer women who received RhIg at delivery compared to no RhIg became sensitized [70 fewer sensitized women per 1,000 (95%CI: 67 to 71 fewer); I2 = 73%]), due to very low certainty of the evidence, the magnitude of the treatment effect may be overestimated. The certainty of the evidence was very low for most outcomes often due to high risk of bias (e.g., randomization method, allocation concealment, selective reporting) and imprecision (i.e., few events and small sample sizes). There is limited evidence on prophylaxis for invasive fetal procedures (e.g. amniocentesis) in the comparative literature, and few studies reported adverse events. CONCLUSION: Serious risk of bias and low to very low certainty of the evidence is found in existing RCTs and comparative observational studies addressing optimal effectiveness of Rh immunoprophylaxis. Guideline development committees should exercise caution when assessing the strength of the recommendations that inform and influence clinical practice in this area.


Assuntos
Fatores Imunológicos/administração & dosagem , Cuidado Pós-Natal/normas , Cuidado Pré-Natal/normas , Isoimunização Rh/prevenção & controle , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Feminino , Abordagem GRADE , Humanos , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Isoimunização Rh/imunologia
7.
Rheumatol Int ; 40(12): 2015-2021, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32945944

RESUMO

The objective of this study is to describe the characteristics and outcomes of rheumatic and musculoskeletal disease (RMD) patients who were treated with rituximab and had suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this descriptive study, RMD patients who were treated with rituximab in the last 12 months at the Rheumatology Department of our hospital were screened for SARS-CoV-2 infection via telephone interview and a comprehensive review of clinical health records (01/02/2020-26/05/2020). Those with probable or confirmed SARS-CoV-2 infection were included. In total, 76 patients were screened. Of these, 13 (17.1%) had suspected or confirmed SARS-CoV-2 infection. With regard to these 13 patients, the median age at coronavirus disease (COVID-19) diagnosis was 68 years (range 28-76 years) and 8 (61.5%) were female. Five patients had rheumatoid arthritis, three had systemic vasculitis, two had Sjögren syndrome, and two had systemic lupus erythematosus. Additionally, seven patients (53.8%) had pulmonary involvement secondary to RMD. Eight patients (61.5%) developed severe disease leading to hospitalization, and seven developed bilateral pneumonia and respiratory insufficiency. Of the eight hospitalized patients, five (62.5%) fulfilled the acute respiratory distress syndrome criteria and three developed a critical disease and died. Our cohort had a high rate of severe disease requiring hospitalization (61.5%), with bilateral pneumonia and hyperinflammation leading to a high mortality rate (23.1%). Treatment with rituximab should be considered a possible risk factor for unfavorable outcomes in COVID-19 patients with RMD. However, further study is required to confirm this association.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Fatores Imunológicos/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pneumonia Viral/mortalidade , Rituximab/efeitos adversos , Adulto , Idoso , Artrite Reumatoide/complicações , Betacoronavirus , Contraindicações de Medicamentos , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Estudos Retrospectivos , Rituximab/administração & dosagem , Índice de Gravidade de Doença
8.
Front Immunol ; 11: 1660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760407

RESUMO

The current outbreak of viral pneumonia, caused by novel coronavirus SARS-CoV-2, is the focus of worldwide attention. The WHO declared the COVID-19 outbreak a pandemic event on Mar 12, 2020, and the number of confirmed cases is still on the rise worldwide. While most infected individuals only experience mild symptoms or may even be asymptomatic, some patients rapidly progress to severe acute respiratory failure with substantial mortality, making it imperative to develop an efficient treatment for severe SARS-CoV-2 pneumonia alongside supportive care. So far, the optimal treatment strategy for severe COVID-19 remains unknown. Intravenous immunoglobulin (IVIg) is a blood product pooled from healthy donors with high concentrations of immunoglobulin G (IgG) and has been used in patients with autoimmune and inflammatory diseases for more than 30 years. In this review, we aim to highlight the known mechanisms of immunomodulatory effects of high-dose IVIg therapy, the immunopathological hypothesis of viral pneumonia, and the clinical evidence of IVIg therapy in viral pneumonia. We then make cautious therapeutic inferences about high-dose IVIg therapy in treating severe COVID-19. These inferences may provide relevant and useful insights in order to aid treatment for COVID-19.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Adulto , Animais , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Facilitadores , Criança , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Fragmentos Fab das Imunoglobulinas/metabolismo , Fragmentos Fc das Imunoglobulinas/metabolismo , Imunoglobulina G/administração & dosagem , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pandemias , Pneumonia Viral/virologia
9.
J Clin Pharmacol ; 60(10): 1275-1293, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32779201

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by infection with SARS-CoV-2 has led to more than 600 000 deaths worldwide. Patients with severe disease often experience acute respiratory distress characterized by upregulation of multiple cytokines. Immunomodulatory biological therapies are being evaluated in clinical trials for the management of the systemic inflammatory response and pulmonary complications in patients with advanced stages of COVID-19. In this review, we summarize the clinical pharmacology considerations in the development of immunomodulatory therapeutic proteins for mitigating the heightened inflammatory response identified in COVID-19.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Proteínas/administração & dosagem , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Desenvolvimento de Medicamentos , Humanos , Fatores Imunológicos/farmacologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Proteínas/imunologia , Proteínas/farmacologia
10.
Nephrology (Carlton) ; 25(11): 845-849, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32776624

RESUMO

COVID-19 remains a global pandemic with more than 10 million cases and half a million deaths worldwide. The disease manifestations in patients with chronic kidney disease and especially those on haemodialysis are still being understood, with only a few overseas case series, and small observational trials thus far. It appears that the disease is more severe in this patient cohort. Part of the pathophysiology of severe COVID-19 is related to accompanying cytokine release syndrome (CRS). Tocilizumab, an interleukin-6 inhibitor, has been trialled for treatment of CRS in COVID-19, but not yet approved. We present a case of an Australian patient on long-term haemodialysis with severe COVID-19 who was successfully treated with Tocilizumab. The peak of her illness was on day 7, with a C-reactive protein of 624 mg/L (reference < 5 mg/L), ferritin of 5293 ng/mL (reference 30-500 ng/mL), and interleukin-6 level 1959.7 pg/mL, consistent with CRS. She was severely hypoxic on a ventilator, with rising inotropic requirements. With the use of Tocilizumab, there was a significant and immediate response in her inflammatory markers, and she made a steady recovery. The patient was discharged home 6 weeks after presentation.


Assuntos
Anemia , Anticorpos Monoclonais Humanizados/administração & dosagem , Infecções por Coronavirus , Síndrome da Liberação de Citocina , Interleucina-6 , Falência Renal Crônica , Pandemias , Pneumonia Viral , Idoso , Anemia/etiologia , Anemia/terapia , Transfusão de Sangue/métodos , Proteína C-Reativa/análise , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/terapia , Síndrome da Liberação de Citocina/virologia , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Monitorização Imunológica/métodos , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Diálise Renal/métodos , Respiração Artificial/métodos , Resultado do Tratamento
11.
Am J Trop Med Hyg ; 103(4): 1590-1592, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32830642

RESUMO

The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.


Assuntos
Infecções por Coronavirus/parasitologia , Diabetes Mellitus/parasitologia , Hipertensão/parasitologia , Doenças do Sistema Nervoso Periférico/parasitologia , Pneumonia Viral/parasitologia , Strongyloides stercoralis/patogenicidade , Estrongiloidíase/parasitologia , Corticosteroides/administração & dosagem , Idoso , Animais , Anti-Helmínticos/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Betacoronavirus/patogenicidade , Coinfecção , Connecticut , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/imunologia , Diabetes Mellitus/virologia , Equador , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Hipertensão/virologia , Fatores Imunológicos/administração & dosagem , Masculino , Pandemias , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/imunologia , Estrongiloidíase/virologia
12.
BMJ Case Rep ; 13(7)2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641309
13.
BMJ Case Rep ; 13(7)2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641442

RESUMO

We report on a patient with coronavirus disease 2019 (COVID-19) and decompensated cirrhosis who experienced a favourable outcome of severe immune thrombocytopaenic purpura (ITP) after administration of intravenous immunoglobulin and high-dose dexamethasone. The present case suggests that it is reasonable to evoke ITP in case of profound thrombocytopaenia in a patient with COVID-19.


Assuntos
Infecções por Coronavirus , Glucocorticoides/administração & dosagem , Imunoglobulinas Intravenosas/administração & dosagem , Cirrose Hepática Alcoólica , Obesidade , Pandemias , Pneumonia Viral , Púrpura Trombocitopênica Idiopática , Adulto , Betacoronavirus/isolamento & purificação , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Humanos , Hipóxia/diagnóstico , Hipóxia/etiologia , Fatores Imunológicos/administração & dosagem , Cirrose Hepática Alcoólica/diagnóstico , Cirrose Hepática Alcoólica/epidemiologia , Masculino , Obesidade/diagnóstico , Obesidade/epidemiologia , Oxigenoterapia/métodos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/etiologia , Púrpura Trombocitopênica Idiopática/fisiopatologia , Púrpura Trombocitopênica Idiopática/terapia , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
14.
Proc Natl Acad Sci U S A ; 117(32): 18951-18953, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32699149

RESUMO

Around the tenth day after diagnosis, ∼20% of patients with coronavirus disease 2019 (COVID-19)-associated pneumonia evolve toward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a "cytokine storm." Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19-associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg⋅d-1 for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P < 0.01), with no deaths, significant decreases in oxygen requirements (P < 0.05), and more days without invasive mechanical ventilation (P < 0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of 1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyperinflammatory respiratory failure in COVID-19 patients.


Assuntos
Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Insuficiência Respiratória/tratamento farmacológico , Idoso , Anti-Inflamatórios/administração & dosagem , Estudos de Casos e Controles , Infecções por Coronavirus/complicações , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Injeções Intravenosas , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/etiologia , Insuficiência Respiratória/etiologia
15.
Nat Commun ; 11(1): 3584, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681091

RESUMO

Responses to immunotherapy are uncommon in estrogen receptor (ER)-positive breast cancer and to date, lack predictive markers. This randomized phase II study defines safety and response rate of epigenetic priming in ER-positive breast cancer patients treated with checkpoint inhibitors as primary endpoints. Secondary and exploratory endpoints included PD-L1 modulation and T-cell immune-signatures. 34 patients received vorinostat, tamoxifen and pembrolizumab with no excessive toxicity after progression on a median of five prior metastatic regimens. Objective response was 4% and clinical benefit rate (CR + PR + SD > 6 m) was 19%. T-cell exhaustion (CD8+ PD-1+/CTLA-4+) and treatment-induced depletion of regulatory T-cells (CD4+ Foxp3+/CTLA-4+) was seen in tumor or blood in 5/5 patients with clinical benefit, but only in one non-responder. Tumor lymphocyte infiltration was 0.17%. Only two non-responders had PD-L1 expression >1%. This data defines a novel immune signature in PD-L1-negative ER-positive breast cancer patients who are more likely to benefit from immune-checkpoint and histone deacetylase inhibition (NCT02395627).


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Imunoterapia , Linfócitos T/imunologia , Tamoxifeno/administração & dosagem , Vorinostat/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Receptores Estrogênicos/genética , Receptores Estrogênicos/imunologia , Linfócitos T/efeitos dos fármacos , Resultado do Tratamento
16.
Cancer Treat Rev ; 89: 102065, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32653806

RESUMO

To date, much progress has been made in early-stage extranodal NK/T-cell lymphoma (ENKTCL), and risk-adapted therapy with radiotherapy (RT) alone for the low-risk group and RT combined with asparaginase-based chemotherapy (CT) for the high-risk group yields favorable outcomes. However, optimal treatment strategies have not been defined yet for advanced-stage ENKTCL. Historically, ENKTCL responded poorly to conventional anthracycline-based chemotherapy probably because of inherent multidrug resistance (MDR). The fact that ENKTCL cells lack asparagine synthetase (ASNS) activity warranted the use of L-asparaginase or pegaspargase as frontline chemotherapies. Even though, due to high mortality of the disease, approximately 50% patients failing the frontline therapy arrived at dismal clinical outcomes with a median progression-free survival (PFS) less than 8 months. As distinctive molecular and biological subgroups are increasingly discovered within the disease entity of ENKTCL, novel targeted therapies and immunotherapy are of the urgent need for those heterogeneous subgroups. In this review, we sought to summarize the preclinical and clinical results of 6 categories of promising targeted therapy and immunotherapy for the treatment of ENKTCL, including monoclonal antibodies, immune checkpoint inhibitors, small-molecular inhibitors, epigenetic therapy, immunomodulatory drugs, and adoptive T-cell therapy, and these might change the landscape of treatment for ENKTCL in the near future.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/terapia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/farmacologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacologia , Imunoterapia/métodos , Imunoterapia Adotiva , Terapia de Alvo Molecular/métodos , Bibliotecas de Moléculas Pequenas/administração & dosagem , Bibliotecas de Moléculas Pequenas/farmacologia
17.
Clin Nutr ESPEN ; 38: 65-66, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32690179

RESUMO

BACKGROUND & AIMS: The COVID-19 infection can lead to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly affecting patients aged 60 and older. Preliminary data suggest that the nutritional status can change the course of the infection, and on the matter, zinc is crucial for growth, development, and the maintenance of immune function. In the absence of treatment for this virus, there is an urgent need to find alternative methods that can contribute to control of disease. The aim of this paper is to establish the relation between zinc and COVID-19. METHODS AND RESULTS: From the prior scientific knowledge, we have performed a review of the literature and examine the role of zinc in immune function in the infection by COVID-19. Our findings are that the zinc as an anti-inflammatory agent may help to optimize immune function and reduce the risk of infection. CONCLUSIONS: Zinc supplementation can be a useful strategy to reduce the global burden of infection in the elderly, there is a need the increased reporting to improve our understanding of COVID-19 and the care of affected patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Imunidade/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Oligoelementos/administração & dosagem , Zinco/administração & dosagem , Idoso , Infecções por Coronavirus/imunologia , Feminino , Humanos , Fatores Imunológicos/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Oligoelementos/imunologia , Zinco/imunologia
18.
Gene ; 759: 144987, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32712065

RESUMO

BACKGROUND: The immune response is influenced by the administration of omega-3 polyunsaturated fatty acids (PUFA). Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE) are affected by PUFA. The combination of evening primrose/hemp seed oil (EPO/HSO) has essential fatty acids (EFAs) for human optimal health due to the favorable ratio of omega-6/omega-3 and antioxidantal properties. The study was conducted to evaluate the effects of EPO/HSO on improving the membrane fatty acids composition of spleen and blood cells and immunologic factors in compared to rapamycin (RAPA) in the EAE model. METHODS AND MATERIALS: Chronic-EAE was induced by induction of MOG in C57BL/6J mice (female, age: 6-8 weeks, weight 18-21). Mice were assigned to 5 groups (6/group) to evaluate the therapeutic effects of EPO/HSO supplement in comparison with rapamycin: A group; EPO/HSO + RAPA, B group; RAPA, C group; EPO/HSO. Results were compared to two control groups (EAE and naive). The fatty acid profile of the spleen and blood cell membrane was evaluated. Real-time-polymerase chain reaction was used for the evaluate the genes expression levels of interleukin (IL) -4, IL-5, and IL-13 in lymphocytes. Also, IL-4 of serum was evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our findings indicated that EPO/HSO therapy significantly increased the percentage of essential fatty acids in cell membrane of the spleen and blood. The relative expression of IL-4, IL-5, and IL-13 genes in lymphocytes and serum level of IL-4 was significantly increased in the HSO/EPO treated group versus other groups. CONCLUSION: These results point to potential therapeutic effects on the repair of the structure of cell membranes and suppression of inflammation by EPO/HSO in EAE.


Assuntos
Antioxidantes/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Ácidos Graxos Essenciais/metabolismo , Fatores Imunológicos/uso terapêutico , Interleucinas/metabolismo , Óleos Vegetais/uso terapêutico , Sirolimo/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Cannabis/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Suplementos Nutricionais , Combinação de Medicamentos , Feminino , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacologia , Lipídeos de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Óleos Vegetais/administração & dosagem , Primula/química , Sirolimo/administração & dosagem
19.
Int J Antimicrob Agents ; 56(3): 106103, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32712333

RESUMO

This systemic review and meta-analysis aimed to assess the efficacy of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Candidate studies up to 24 May 2020 were identified from PubMed, Cochrane Library, Embase, medRxiv and bioRxiv. Treatment outcomes included mortality, risk of intensive care unit (ICU) admission and the requirement for mechanical ventilation (MV). Seven retrospective studies involving 592 adult patients with severe COVID-19, including 240 in the tocilizumab group and 352 in the control group, were enrolled. All-cause mortality of severe COVID-19 patients among the tocilizumab group was 16.3% (39/240), which was lower than that in the control group (24.1%; 85/352). However, the difference did not reach statistical significance [risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.31-1.22; I2 = 68%]. Additionally, risk of ICU admission was similar between the tocilizumab and control groups (35.1% vs. 15.8%; RR = 1.51, 95% CI 0.33-6.78; I2 = 86%). The requirement for MV was similar between the tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82, 95% CI 0.14-4.94; I2 = 91%). However, these non-significant differences between the tocilizumab and control groups may have been the result of baseline characteristics of the tocilizumab group, which were more severe than those of the control group. Based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19. Therefore, further recommendation of tocilizumab for COVID-19 cases should be halted until high-quality evidence from randomised controlled trials is available.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Antivirais/administração & dosagem , Infecções por Coronavirus/terapia , Fatores Imunológicos/administração & dosagem , Pneumonia Viral/terapia , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antivirais/efeitos adversos , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/etiologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/mortalidade , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/terapia , Síndrome da Liberação de Citocina/virologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Esquema de Medicação , Humanos , Fatores Imunológicos/efeitos adversos , Unidades de Terapia Intensiva , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/etiologia , Infecções Oportunistas/imunologia , Infecções Oportunistas/mortalidade , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Respiração Artificial , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
20.
Int J Antimicrob Agents ; 56(3): 106101, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32687949

RESUMO

The coronavirus infection (COVID-19) has turned into a global catastrophe and there is an intense search for effective drug therapy. Of all the potential therapies, chloroquine and hydroxychloroquine have been the focus of tremendous public attention. Both drugs have been used in the treatment and prophylaxis of malaria. Long-term use of hydroxychloroquine is the cornerstone in the treatment of several auto-immune disorders. There is convincing evidence that hydroxychloroquine has strong in vitro antiviral activity against SARS-CoV-2. A few small uncontrolled trials and several anecdotal reports have shown conflicting results of such drug therapy in COVID-19. However, the results of preliminary large-scale randomized controlled trials have failed to show any survival benefit of such drug therapy in COVID-19. Despite the lack of such evidence, hydroxychloroquine has been used as a desperate attempt for prophylaxis and treatment of COVID-19. The drug has wide-ranging drug interactions and potential cardiotoxicity. Indiscriminate unsupervised use can expose the public to serious adverse drug effects.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , Cloroquina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Hidroxicloroquina/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/imunologia , Cloroquina/efeitos adversos , Ensaios Clínicos como Assunto , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Esquema de Medicação , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Hidroxicloroquina/efeitos adversos , Fatores Imunológicos/efeitos adversos , Pandemias/prevenção & controle , Pneumonia Viral/mortalidade , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Análise de Sobrevida , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
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