Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23.728
Filtrar
1.
Comput Math Methods Med ; 2020: 1391583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029193

RESUMO

Purpose: We aimed to analyze and evaluate the safety signals of ribavirin-interferon combination through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS), so as to provide reference for the rationale use of these agents in the management of relevant toxicities emerging in patients with novel coronavirus pneumonia (COVID-19). Methods: Reports to the FAERS from 1 January 2004 to 8 March 2020 were analyzed. The proportion of report ratio (PRR), reporting odds ratio (ROR), and Bayesian confidence interval progressive neural network (BCPNN) method were used to detect the safety signals. Results: A total of 55 safety signals were detected from the top 250 adverse event reactions in 2200 reports, but 19 signals were not included in the drug labels. All the detected adverse event reactions were associated with 13 System Organ Classes (SOC), such as gastrointestinal, blood and lymph, hepatobiliary, endocrine, and various nervous systems. The most frequent adverse events were analyzed, and the results showed that females were more likely to suffer from anemia, vomiting, neutropenia, diarrhea, and insomnia. Conclusion: The ADE (adverse drug event) signal detection based on FAERS is helpful to clarify the potential adverse events related to ribavirin-interferon combination for novel coronavirus therapy; clinicians should pay attention to the adverse reactions of gastrointestinal and blood systems, closely monitor the fluctuations of the platelet count, and carry out necessary mental health interventions to avoid serious adverse events.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Interferons/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Ribavirina/efeitos adversos , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Algoritmos , Teorema de Bayes , Mineração de Dados , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Interferons/administração & dosagem , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Razão de Chances , Pandemias , Segurança do Paciente , Ribavirina/administração & dosagem , Adulto Jovem
2.
Medicine (Baltimore) ; 99(36): e21803, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899009

RESUMO

RATIONALE: Complex immune dysregulation in interferon (IFN) and T cell response has been observed in human immunodeficiency virus (HIV-1)-infected patients as well as in coronavirus disease-2019 (COVID-19) patients. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)/HIV-1 coinfection has been described in only few cases worldwide and no data are available on immunological outcomes in HIV-1-patients infected with SARS-CoV-2. Hence, this study aims to compare type I IFN response and T cell activation levels between a SARS-CoV-2/HIV-1-coinfected female patient and age-matched HIV-1-positive or uninfected women. PATIENT CONCERNS: A 52-year-old woman diagnosed with SARS-CoV-2/HIV-1 coinfection, ten HIV-1-positive women and five age-matched-healthy individuals were enrolled in this study. DIAGNOSES: SARS-CoV-2 infection caused severe pneumonia in the second week of illness in HIV-1-positive patient under protease inhibitors. Chest high-resolution computed tomography images of the SARS-CoV-2/HIV-1-coinfected patient showed bilateral ground-glass opacities. INTERVENTIONS: SARS-CoV-2/HIV-1-coinfected female patient under darunavir/cobicistat regimen received a 7-days hydroxychloroquine therapy. Analysis of IFNα/ß mRNA levels and CD4 and CD8 T cell (CD38, human leukocyte antigen-DR [HLA-DR], CD38 HLA-DR) frequencies were performed by RT/real-time PCR assays and flow cytometry, respectively. Median relative difference (MRD) was calculated for each immunological variable. For values greater than reference, MRD should be a positive number and for values that are smaller, MRD should be negative. OUTCOMES: The severe pneumonia observed in SARS-CoV-2/HIV-1-positive patient under protease inhibitors was reversed by a 7-days hydroxychloroquine therapy. At the end of treatment, on day 7, patient reported resolution of fever, normalization of respiratory rate (14 breaths/min), and improved oxygen arterial pressure with a FiO2 of 30%. MRD values for IFNα/ß and CD4 and CD8 T cells expressing CD38 and/or HLA-DR found in SARS-CoV-2-/HIV-1-coinfected woman were approximatively equal to 0 when refereed respectively to HIV-1-positive female patients [MRDs IFNα/ß: median -0.2545 (range: -0.5/0.1); T cells: median -0.11 (range: -0.8/1.3)] and ≥ 6 when referred to healthy individuals [MRDs IFNα/ß: median 28.45 (range: 15/41.9); T cells: median 10 (range 6/22)]. LESSONS: These results indicate that SARS-CoV-2 infection in HIV-1-positive female patient was associated with increased levels of IFNα/ß-mRNAs and T cell activation compared to healthy individuals.


Assuntos
Infecções por Coronavirus/complicações , Infecções por HIV/complicações , Pneumonia Viral/complicações , Síndrome Respiratória Aguda Grave/complicações , Antirretrovirais/uso terapêutico , Betacoronavirus , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Estudos de Casos e Controles , Infecções por Coronavirus/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Hidroxicloroquina/uso terapêutico , Interferons/sangue , Ativação Linfocitária , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , RNA Mensageiro , Reação em Cadeia da Polimerase em Tempo Real , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia
4.
mBio ; 11(5)2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913009

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is a recently emerged respiratory coronavirus that has infected >23 million people worldwide with >800,000 deaths. Few COVID-19 therapeutics are available, and the basis for severe infections is poorly understood. Here, we investigated properties of type I (ß), II (γ), and III (λ1) interferons (IFNs), potent immune cytokines that are normally produced during infection and that upregulate IFN-stimulated gene (ISG) effectors to limit virus replication. IFNs are already in clinical trials to treat COVID-19. However, recent studies highlight the potential for IFNs to enhance expression of host angiotensin-converting enzyme 2 (ACE2), suggesting that IFN therapy or natural coinfections could exacerbate COVID-19 by upregulating this critical virus entry receptor. Using a cell line model, we found that beta interferon (IFN-ß) strongly upregulated expression of canonical antiviral ISGs, as well as ACE2 at the mRNA and cell surface protein levels. Strikingly, IFN-λ1 upregulated antiviral ISGs, but ACE2 mRNA was only marginally elevated and did not lead to detectably increased ACE2 protein at the cell surface. IFN-γ induced the weakest ISG response but clearly enhanced surface expression of ACE2. Importantly, all IFN types inhibited SARS-CoV-2 replication in a dose-dependent manner, and IFN-ß and IFN-λ1 exhibited potent antiviral activity in primary human bronchial epithelial cells. Our data imply that type-specific mechanisms or kinetics shape IFN-enhanced ACE2 transcript and cell surface levels but that the antiviral action of IFNs against SARS-CoV-2 counterbalances any proviral effects of ACE2 induction. These insights should aid in evaluating the benefits of specific IFNs, particularly IFN-λ, as repurposed therapeutics.IMPORTANCE Repurposing existing, clinically approved, antiviral drugs as COVID-19 therapeutics is a rapid way to help combat the SARS-CoV-2 pandemic. Interferons (IFNs) usually form part of the body's natural innate immune defenses against viruses, and they have been used with partial success to treat previous new viral threats, such as HIV, hepatitis C virus, and Ebola virus. Nevertheless, IFNs can have undesirable side effects, and recent reports indicate that IFNs upregulate the expression of host ACE2 (a critical entry receptor for SARS-CoV-2), raising the possibility that IFN treatments could exacerbate COVID-19. Here, we studied the antiviral- and ACE2-inducing properties of different IFN types in both a human lung cell line model and primary human bronchial epithelial cells. We observed differences between IFNs with respect to their induction of antiviral genes and abilities to enhance the cell surface expression of ACE2. Nevertheless, all the IFNs limited SARS-CoV-2 replication, suggesting that their antiviral actions can counterbalance increased ACE2.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Interferon Tipo I/farmacologia , Interferon gama/farmacologia , Interferons/farmacologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Idoso , Animais , Betacoronavirus/imunologia , Linhagem Celular , Chlorocebus aethiops , Feminino , Humanos , Imunoterapia/métodos , Interferon Tipo I/efeitos adversos , Interferon gama/efeitos adversos , Interferons/efeitos adversos , Pandemias , Peptidil Dipeptidase A/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores Virais/metabolismo , Mucosa Respiratória/citologia , Mucosa Respiratória/virologia , Regulação para Cima/efeitos dos fármacos , Células Vero , Replicação Viral/efeitos dos fármacos
5.
Recenti Prog Med ; 111(9): 480-486, 2020 09.
Artigo em Italiano | MEDLINE | ID: mdl-32914775

RESUMO

At the end of March 2020, just over a month after the first ascertained case of CoViD-19 infection in Italy, the first reports of acute lesions of acro-ischemia appeared, especially in pre-adolescents and adolescents. These manifestations have been called in the course of these months in various ways, from "acro-ischemia acuta", "erythema pernio", "chilblains", up to characterize them more recently as "CoViD Toes". Clinical manifestations do not usually associate with other typical symptoms of Covid-19 and do not find a classical and defined serological antibody response (IgG and IgM). From a clinical point of view it is a localized and self-resolving problem of an interesting and relatively new pathogenetic model of disease in relation to a viral agent. Future studies must make us understand if there is in this specific condition a low viral load is not detectable by current methods and if this explains the inability to produce an adequate immune response for CoViD-19. It is important to determine whether the interferon immune response in some subjects can be the cause of both the low viremia and the endothelial damage so localized in the acral-site, as happens in other models of diseases (chilblain-lupus like). On the contrary, some authors believe that the acral lesions are attributable to chilblains caused by a series of favourable environmental conditions due to forced enclosure. We report the descriptive experience of 14 cases of acro-ischemia in children and adolescents observed in the territorial area of Ravenna and Rimini. The cases were subjected to the nasopharyngeal swab and to the search for antibodies with ELISA method for CoViD-19 both with negative results.


Assuntos
Infecções por Coronavirus/epidemiologia , Interferons/imunologia , Isquemia/epidemiologia , Estilo de Vida , Pneumonia Viral/epidemiologia , Adolescente , Pérnio/epidemiologia , Pérnio/etiologia , Pérnio/imunologia , Criança , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Feminino , Humanos , Isquemia/etiologia , Isquemia/imunologia , Itália/epidemiologia , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Quarentena , Dedos do Pé
6.
Biochimie ; 177: 50-52, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32805303

RESUMO

Various interferon (IFN)-inducible transmembrane (IFITM) proteins are known to be expressed in human tissues though only IFITM 1-3 are inducible by IFN. Numerous studies have shown that activation of IFITM3 could suppress infection by influenza and coronaviruses such as the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In view of the potential application of IFITM proteins' induction to target SARS-CoV-2 infection that causes COVID-19, this article layout insights into the known antiviral mechanisms and therapeutic agents related to IFITM. Blocking viral entry through various mechanisms and the potential application of the FDA approved immunosuppressant agent, mycophenolic acid, as inducer of IFITM3 are among those discussed.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Interferons/farmacologia , Proteínas de Membrana/efeitos dos fármacos , Ácido Micofenólico/farmacologia , Pneumonia Viral/tratamento farmacológico , Proteínas de Ligação a RNA/efeitos dos fármacos , Animais , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Humanos , Imunossupressores/farmacologia , Proteínas de Membrana/imunologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Proteínas de Ligação a RNA/imunologia
7.
Science ; 369(6504): 626-627, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32764056
8.
Int J Biol Sci ; 16(14): 2479-2489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32792851

RESUMO

The emergence of SARS-CoV-2 virus and its associated disease COVID-19 have triggered significant threats to public health, in addition to political and social changes. An important number of studies have reported the onset of symptoms compatible with pneumonia accompanied by coagulopathy and lymphocytopenia during COVID-19. Increased cytokine levels, the emergence of acute phase reactants, platelet activation and immune checkpoint expression are some of the biomarkers postulated in this context. As previously observed in prolonged sepsis, T-cell exhaustion due to SARS-CoV-2 and even their reduction in numbers due to apoptosis hinder the response to the infection. In this review, we synthesized the immune changes observed during COVID-19, the role of immune molecules as severity markers for patient stratification and their associated therapeutic options.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Sepse/fisiopatologia , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Biomarcadores , Transtornos da Coagulação Sanguínea/imunologia , Citocinas/metabolismo , Humanos , Sistema Imunitário , Imunidade Inata , Interferons/metabolismo , Linfopenia/imunologia , Pandemias , Fenótipo , Ativação Plaquetária
9.
Brasília; s.n; 7 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117973

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 12 artigos e 4 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Sistema Renina-Angiotensina , Avaliação da Tecnologia Biomédica , Dexametasona/uso terapêutico , Vacinas/uso terapêutico , Cloroquina/uso terapêutico , Interferons/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Ritonavir/uso terapêutico , Combinação de Medicamentos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Lopinavir/uso terapêutico , Rituximab/uso terapêutico , Hidroxicloroquina/uso terapêutico
10.
Brasília; s.n; 5 ago 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117760

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 11 artigos e 6 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Antivirais/uso terapêutico , Avaliação da Tecnologia Biomédica , Imunoglobulinas/uso terapêutico , Metilprednisolona/uso terapêutico , Colchicina/uso terapêutico , Metotrexato/uso terapêutico , Estudos de Coortes , Interferons/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Oseltamivir/uso terapêutico , Células-Tronco Mesenquimais , Interferon alfa-2/uso terapêutico , Glucocorticoides/uso terapêutico , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico
11.
Nat Rev Immunol ; 20(10): 585-586, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32788708
12.
Arch Virol ; 165(10): 2165-2176, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32740830

RESUMO

The PI3K/Akt signalling pathway is a crucial signalling cascade that regulates transcription, protein translation, cell growth, proliferation, cell survival, and metabolism. During viral infection, viruses exploit a variety of cellular pathways, including the well-known PI3K/Akt signalling pathway. Conversely, cells rely on this pathway to stimulate an antiviral response. The PI3K/Akt pathway is manipulated by a number of viruses, including DNA and RNA viruses and retroviruses. The aim of this review is to provide up-to-date information about the role of the PI3K-Akt pathway in infection with members of five different families of negative-sense ssRNA viruses. This pathway is hijacked for viral entry, regulation of endocytosis, suppression of premature apoptosis, viral protein expression, and replication. Although less common, the PI3K/Akt pathway can be downregulated as an immunomodulatory strategy or as a mechanism for inducing autophagy. Moreover, the cell activates this pathway as an antiviral strategy for interferon and cytokine production, among other strategies. Here, we present new data concerning the role of this pathway in infection with the paramyxovirus Newcastle disease virus (NDV). Our data seem to indicate that NDV uses the PI3K/Akt pathway to delay cell death and increase cell survival as a means of improving its replication. The interference of negative-sense ssRNA viruses with this essential pathway might have implications for the development of antiviral therapies.


Assuntos
Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Fosfatidilinositol 3-Quinase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Infecções por Vírus de RNA/genética , Apoptose/genética , Autofagia/genética , Autofagia/imunologia , Citocinas/genética , Citocinas/imunologia , Endocitose/genética , Endocitose/imunologia , Filoviridae/genética , Filoviridae/metabolismo , Filoviridae/patogenicidade , Interações Hospedeiro-Patógeno/imunologia , Interferons/genética , Interferons/imunologia , Orthomyxoviridae/genética , Orthomyxoviridae/metabolismo , Orthomyxoviridae/patogenicidade , Paramyxoviridae/genética , Paramyxoviridae/metabolismo , Paramyxoviridae/patogenicidade , Fosfatidilinositol 3-Quinase/imunologia , Pneumovirinae/genética , Pneumovirinae/metabolismo , Pneumovirinae/patogenicidade , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-akt/imunologia , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/virologia , Rhabdoviridae/genética , Rhabdoviridae/metabolismo , Rhabdoviridae/patogenicidade , Transdução de Sinais , Proteínas Virais/genética , Proteínas Virais/imunologia , Internalização do Vírus , Replicação Viral
13.
PLoS Pathog ; 16(8): e1008678, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760119

RESUMO

GWAS, immune analyses and biomarker screenings have identified host factors associated with in vivo HIV-1 control. However, there is a gap in the knowledge about the mechanisms that regulate the expression of such host factors. Here, we aimed to assess DNA methylation impact on host genome in natural HIV-1 control. To this end, whole DNA methylome in 70 untreated HIV-1 infected individuals with either high (>50,000 HIV-1-RNA copies/ml, n = 29) or low (<10,000 HIV-1-RNA copies/ml, n = 41) plasma viral load (pVL) levels were compared and identified 2,649 differentially methylated positions (DMPs). Of these, a classification random forest model selected 55 DMPs that correlated with virologic (pVL and proviral levels) and HIV-1 specific adaptive immunity parameters (IFNg-T cell responses and neutralizing antibodies capacity). Then, cluster and functional analyses identified two DMP clusters: cluster 1 contained hypo-methylated genes involved in antiviral and interferon response (e.g. PARP9, MX1, and USP18) in individuals with high viral loads while in cluster 2, genes related to T follicular helper cell (Tfh) commitment (e.g. CXCR5 and TCF7) were hyper-methylated in the same group of individuals with uncontrolled infection. For selected genes, mRNA levels negatively correlated with DNA methylation, confirming an epigenetic regulation of gene expression. Further, these gene expression signatures were also confirmed in early and chronic stages of infection, including untreated, cART treated and elite controllers HIV-1 infected individuals (n = 37). These data provide the first evidence that host genes critically involved in immune control of the virus are under methylation regulation in HIV-1 infection. These insights may offer new opportunities to identify novel mechanisms of in vivo virus control and may prove crucial for the development of future therapeutic interventions aimed at HIV-1 cure.


Assuntos
Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/imunologia , Metilação de DNA , Infecções por HIV/imunologia , HIV-1/imunologia , Fatores Reguladores de Interferon/genética , Carga Viral , Antivirais/uso terapêutico , Epigênese Genética , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/genética , Interações Hospedeiro-Patógeno , Humanos , Fatores Reguladores de Interferon/metabolismo , Interferons/metabolismo , Masculino , Linfócitos T Auxiliares-Indutores/imunologia , Replicação Viral
14.
Life Sci ; 258: 118185, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32750438

RESUMO

AIMS: The immune response is essential for the control and resolution of viral infections. Following the outbreak of novel coronavirus disease (COVID-19), several immunotherapies were applied to modulate the immune responses of the affected patients. In this review, we aimed to describe the role of the immune system in response to COVID-19. We also provide a systematic review to collate and describe all published reports of the using immunotherapies, including convalescent plasma therapy, monoclonal antibodies, cytokine therapy, mesenchymal stem cell therapy, and intravenous immunoglobulin and their important outcomes in COVID-19 patients. MATERIAL AND METHODS: A thorough search strategy was applied to identify published research trials in PubMed, Scopus, Medline, and EMBASE from Dec 1, 2019, to May 4, 2020, for studies reporting clinical outcomes of COVID-19 patients treated with immunotherapies along with other standard cares. KEY FINDINGS: From an initial screen of 80 identified studies, 24 studies provided clinical outcome data on the use of immunotherapies for the treatment of COVID-19 patients, including convalescent plasma therapy (33 patients), monoclonal antibodies (55 patients), interferon (31 patients), mesenchymal stem cell therapy (8 patient), and immunoglobulin (63 patients). Except for nine severe patients who died after treatment, most patients were recovered from COVID-19 with improved clinical symptoms and laboratory assessment. SIGNIFICANCE: Based on the available evidence, it seems that treatment with immunotherapy along with other standard cares could be an effective and safe approach to modulate the immune system and improvement of clinical outcomes.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/terapia , Imunoterapia/métodos , Pneumonia Viral/terapia , Anticorpos Monoclonais/uso terapêutico , Infecções por Coronavirus/imunologia , Humanos , Imunização Passiva/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Interferons/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Pandemias , Pneumonia Viral/imunologia , Resultado do Tratamento
15.
Med Hypotheses ; 143: 110153, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763662

RESUMO

Reports from various countries suggest that tobacco smoking might protect from SARS-CoV-2 infection, since the prevalence of smoking in COVID-19 hospitalized patients is lower than in the respective general population. Apart from nicotine or other chemicals contained in tobacco smoke, we propose that a single-stranded RNA virus that infects tobacco leaves, tobacco mosaic virus (TMV), might be implicated in this effect. TMV, though non-pathogenic, is found in smokers' airways, and stimulates adaptive and innate immunity, with release of specific antibodies and interferons. The latter may have preventive and/or therapeutic effects against COVID-19. If confirmed by epidemiological and interventional studies, this might lead to the use of TMV as an immunological adjuvant against SARS-CoV-2 infection and COVID-19 disease.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Modelos Imunológicos , Pandemias , Pneumonia Viral/imunologia , Fumantes , Vírus do Mosaico do Tabaco/imunologia , Produtos do Tabaco/virologia , Fumar Tabaco , Animais , Anticorpos Antivirais/biossíntese , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Resistência à Doença , Humanos , Interferons/biossíntese , Camundongos , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Sistema Respiratório/imunologia , Sistema Respiratório/virologia , Vírus do Mosaico do Tabaco/isolamento & purificação , Fumar Tabaco/epidemiologia , Receptores Toll-Like/imunologia
16.
PLoS One ; 15(8): e0237005, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813740

RESUMO

INTRODUCTION: Interferon (IFN)-free regimens for the treatment of chronic hepatitis C have shown high rates of sustained virological response (SVR) and improved patient-reported outcomes (PROs). The aim of this study was to evaluate the health-related quality of life (HRQoL) and fatigue of patients with chronic hepatitis C (HCV) treated with IFN-free direct-acting antiviral (DAA) agents that achieved SVR following treatment and identify the predictive factors related to HRQoL. METHODS: Prospective cohort study that included patients with HCV treated with DAA who obtained an SVR. The patients answered three self-reported questionnaires (PROs): Short Form 36 (SF-36), the Chronic Liver Diseases Questionnaire (CLDQ), and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire at baseline, weeks 6 and 12 of treatment, and at 12 weeks after therapy. Patients were treated with DAA with or without ribavirin (RBV). The PRO scores were compared using analysis of variance (ANOVA). A comparison of PROs and serum hemoglobin levels was performed between the group that used ribavirin and the one that did not use ribavirin using the t student test. Predictive factors were calculated using a multiple linear regression model. RESULTS: Among the 113 patients selected, 105 presented an SVR and were included in the study, in which, 54% men, 80% genotype 1, 44% cirrhosis and 46% with RBV. At 12 weeks after the end of treatment, there was a significant improvement in the scores of the patient self-reports (PROs) when compared with baseline for the CLDQ (+10.52%, p<0.001), SF-36-Physical Summary (+19%, p<0.001), and FACIT (+17.34%, p<0.001). Patients who used RBV had worse PROs and serum hemoglobin levels compared to the group that did not use RBV (p<0,05). As predictors of worsening of the PROs we had the presence of diabetes mellitus, liver cirrhosis and HIV co-infected. CONCLUSION: Patients treated with IFN free regimens presents significant improvement in PROs. The presence of diabetes mellitus, cirrhosis, and HIV co-infected has a negative effect on HRQoL before, during and after treatment of hepatitis C. The addition of ribavirin to the antiviral regimens used compromises the HRQoL indexes during antiviral therapy.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Brasil , Estudos de Coortes , Fadiga/etiologia , Fadiga/prevenção & controle , Feminino , Hepatite C Crônica/fisiopatologia , Hepatite C Crônica/virologia , Humanos , Interferons/administração & dosagem , Interferons/efeitos adversos , Interferons/uso terapêutico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Qualidade de Vida , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Resposta Viral Sustentada
17.
Int J Antimicrob Agents ; 56(3): 106118, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32738305

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is rapidly advancing across the globe despite drastic public and personal health measures. Antivirals and nutritional supplements have been proposed as potentially useful against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes COVID-19, but few have been clinically established. Lactoferrin (Lf) is a naturally occurring, non-toxic glycoprotein that is orally available as a nutritional supplement and has established in vitro antiviral efficacy against a wide range of viruses, including SARS-CoV, a closely related coronavirus to SARS-CoV-2. Furthermore, Lf possesses unique immunomodulatory and anti-inflammatory effects that may be especially relevant to the pathophysiology of severe COVID-19 cases. Here we review the underlying biological mechanisms of Lf as an antiviral and immune regulator, and propose its unique potential as a preventative and adjunct treatment for COVID-19. We hope that further research and development of Lf nutritional supplementation would establish its role for COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fatores Imunológicos/uso terapêutico , Lactoferrina/uso terapêutico , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Proteoglicanas de Heparan Sulfato/antagonistas & inibidores , Proteoglicanas de Heparan Sulfato/metabolismo , Humanos , Interferons/agonistas , Interferons/biossíntese , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
18.
Biomed Pharmacother ; 129: 110500, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32768975

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19)2 has emerged as a global pandemic. However, as effective treatments for this disease are still unclear, safe and efficient therapies are urgently needed. Qingfei Paidu decoction (QPD)3 is strongly recommended in the Chinese Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 6th Edition). However, clinical research data on the effects of QPD on COVID-19 are scarce. Our study aimed to explore the effects of combined treatment with QPD and Western medicine on COVID-19. METHODS: In this study, 63 patients with confirmed COVID-19 were analyzed. During the first 14 days of hospitalization, patients with deteriorating symptoms were administered QPD along with Western medicine therapy (the antiviral medicine selected from interferon, lopinavir, or arbidol). The clinical characteristics and blood laboratory indices (blood routine, inflammatory factors, and multi-organ biochemical indices) were examined, and the total lung severity scores were evaluated in each patient by reviewing chest computed tomography before treatment and at the end of treatment. RESULTS: Before QPD treatment, the combined treatment group showed higher blood C-reactive protein levels and more severe pulmonary inflammation and clinical symptoms than the Western medicine treatment group. Both groups met the discharge criteria after a similar length of hospitalization. At the end of treatment, circulating white blood cells, total lymphocyte count, and glutamic-oxaloacetic transaminase levels improved dramatically in both groups (P <  0.05). In contrast, C-reactive protein, creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, and blood urea nitrogen levels were improved only in the combined treatment group (P <  0.05), and C-reactive protein and creatine kinase were the most pronounced (P <  0.01). Compared with baseline, at the end of treatment, the proportion of patients with normal values of C-reactive protein, total lymphocyte count, and lactate dehydrogenase were increased in the combined treatment group (P < 0.05), whereas no significant difference was observed in the Western medicine treatment group (P >  0.05). CONCLUSION: The combination of QPD with Western medicine demonstrated significant anti-inflammatory effects compared with those of only Western medicine in patients with mild and moderate COVID-19; however, neither mortality nor length of hospitalization was affected. Moreover, the combined treatment tended to mitigate the extent of multi-organ impairment. Long-term randomized controlled trials with follow-up evaluations are required to confirm the results presented here.


Assuntos
Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Indóis/administração & dosagem , Interferons/administração & dosagem , Tempo de Internação , Lopinavir/administração & dosagem , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/virologia , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
19.
Vet Microbiol ; 247: 108785, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32768229

RESUMO

Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes watery diarrhea, vomiting and mortality in nursing piglets. Type III interferons (IFN-λs) are the major antiviral cytokines in intestinal epithelial cells, the target cells in vivo for PDCoV. In this study, we found that PDCoV infection remarkably inhibited Sendai virus-induced IFN-λ1 production by suppressing transcription factors IRF and NF-κB in IPI-2I cells, a line of porcine intestinal mucosal epithelial cells. We also confirmed that PDCoV infection impeded the activation of IFN-λ1 promoter stimulated by RIG-I, MDA5 and MAVS, but not by TBK1 and IRF1. Although the expression levels of IRF1 and MAVS were not changed, PDCoV infection resulted in reduction of the number of peroxisomes, the platform for MAVS to activate IRF1, and subsequent type III IFN production. Taken together, our study demonstrates that PDCoV suppresses type III IFN responses to circumvent the host's antiviral immunity.


Assuntos
Infecções por Coronavirus/veterinária , Células Epiteliais/imunologia , Células Epiteliais/virologia , Interações Hospedeiro-Patógeno/imunologia , Interferons/antagonistas & inibidores , Animais , Linhagem Celular , Coronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Fator Regulador 1 de Interferon/antagonistas & inibidores , Fator Regulador 1 de Interferon/imunologia , Interferons/imunologia , Intestinos/citologia , Intestinos/virologia , Rim/citologia , Rim/virologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , Vírus Sendai/imunologia , Transdução de Sinais/imunologia , Suínos/virologia , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia
20.
Clin Sci (Lond) ; 134(15): 1991-2017, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32749472

RESUMO

The major risk factors to fatal outcome in COVID-19 patients, i.e., elderliness and pre-existing metabolic and cardiovascular diseases (CVD), share in common the characteristic of being chronic degenerative diseases of inflammatory nature associated with defective heat shock response (HSR). The molecular components of the HSR, the principal metabolic pathway leading to the physiological resolution of inflammation, is an anti-inflammatory biochemical pathway that involves molecular chaperones of the heat shock protein (HSP) family during homeostasis-threatening stressful situations (e.g., thermal, oxidative and metabolic stresses). The entry of SARS coronaviruses in target cells, on the other hand, aggravates the already-jeopardized HSR of this specific group of patients. In addition, cellular counterattack against virus involves interferon (IFN)-mediated inflammatory responses. Therefore, individuals with impaired HSR cannot resolve virus-induced inflammatory burst physiologically, being susceptible to exacerbated forms of inflammation, which leads to a fatal "cytokine storm". Interestingly, some species of bats that are natural reservoirs of zoonotic viruses, including SARS-CoV-2, possess an IFN-based antiviral inflammatory response perpetually activated but do not show any sign of disease or cytokine storm. This is possible because bats present a constitutive HSR that is by far (hundreds of times) more intense and rapid than that of human, being associated with a high core temperature. Similarly in humans, fever is a physiological inducer of HSR while antipyretics, which block the initial phase of inflammation, impair the resolution phase of inflammation through the HSR. These findings offer a rationale for the reevaluation of patient care and fever reduction in SARS, including COVID-19.


Assuntos
Betacoronavirus/fisiologia , Quirópteros/imunologia , Infecções por Coronavirus/imunologia , Resposta ao Choque Térmico , Pneumonia Viral/imunologia , Animais , Betacoronavirus/genética , Quirópteros/virologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Infecções por Coronavirus/fisiopatologia , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/imunologia , Humanos , Interferons/imunologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/genética , Pneumonia Viral/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA