Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.479
Filtrar
1.
BMC Infect Dis ; 21(1): 399, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931015

RESUMO

BACKGROUND: As a blood-borne pathogen, hepatitis C virus (HCV) has long been a major threat associated with needle-stick injuries (NSIs) mainly because no vaccine is available for HCV. Following an NSI, we usually test the source patient for HCV antibody (HCV-Ab). Since HCV-Ab positivity does not necessarily indicate current infection, HCV RNA is further examined in patients positive for HCV-Ab. Direct-acting antivirals (DAAs) have enabled us to treat most HCV-infected patients; therefore, we speculate that the rate of HCV RNA positivity among HCV-Ab-positive patients decreased after the emergence of DAAs. This cross-sectional study was performed to investigate the change in the actual HCV RNA positivity rate in source patients before and after the interferon (IFN)-free DAA era. METHODS: This was a cross-sectional study of NSI source patients at a tertiary academic hospital in Japan from 2009 to 2019. IFN-free DAA regimens were first introduced in Japan in 2014. Accordingly, we compared HCV status of NSI source patients that occurred between 2009 and 2014 (the era before IFN-free DAAs) with those that occurred between 2015 and 2019 (the era of IFN-free DAAs) in a tertiary care hospital in Japan. RESULTS: In total, 1435 NSIs occurred, and 150 HCV-Ab-positive patients were analyzed. The proportion of HCV RNA-positive patients significantly changed from 2009 through 2019 (p = 0.005, Cochran-Armitage test). Between 2009 and 2014, 102 source patients were HCV-Ab-positive, 78 of whom were also positive for HCV RNA (76.5%; 95%CI, 67.4-83.6%). Between 2015 and 2019, 48 patients were HCV-Ab-positive, 23 of whom were also positive for HCV RNA (47.9%; 95%CI, 34.5-61.7%; p = 0.0007 compared with 2009-2014). In the era of IFN-free DAAs, 9 of 23 HCV RNA-negative patients (39.1%) and 2 of 22 HCV RNA-positive patients (9.1%) were treated with an IFN-free combination of DAAs (p = 0.0351). Regarding the departments where NSIs occurred, HCV RNA-negative patients were predominant in departments not related to liver diseases in the era of IFN-free DAAs (p = 0.0078, compared with 2009-2014). CONCLUSIONS: Actual HCV RNA positivity in source patients of NSIs decreased after the emergence of IFN-free DAAs. IFN-free DAAs might have contributed to this reduction, and HCV RNA-negative patients were predominant in departments not related to liver diseases in the era of IFN-free DAAs.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/etiologia , Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Idoso , Estudos Transversais , Feminino , Pessoal de Saúde/estatística & dados numéricos , Hepatite C/tratamento farmacológico , Anticorpos Anti-Hepatite C/sangue , Humanos , Incidência , Interferons/uso terapêutico , Japão , Masculino , Pessoa de Meia-Idade , Ferimentos Penetrantes Produzidos por Agulha/tratamento farmacológico , Traumatismos Ocupacionais/epidemiologia , Traumatismos Ocupacionais/etiologia , RNA Viral/sangue , Estudos Retrospectivos , Centros de Atenção Terciária
2.
World J Gastroenterol ; 27(17): 1959-1972, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34007133

RESUMO

The association between chronic hepatitis C (CHC) infection and extrahepatic manifestations (EHMs), particularly cardiometabolic diseases, has been extensively examined. However, there has still been insufficient evaluation for these EHMs after virological cure. Several multidirectional mechanisms have been proposed explaining the ability of hepatitis C virus (HCV) developing EHMs, cardiometabolic ones, as well as the effect of antiviral therapy to resolve these EHMs. Data on these manifestations after achieving sustained virologic response (SVR) are still conflicting. However, current evidence suggests that reversal of hepatic steatosis and its coexistent hypocholesterolemia after successful viral eradication led to unfavorable lipid profile, which increases cardiovascular disease (CVD) risk. Additionally, most observations showed that metabolic alterations, such as insulin resistance and diabetes mellitus (DM), undergo some degree of reduction after viral clearance. These changes seem HCV-genotype dependent. Interferon-based antiviral therapy and direct acting antiviral drugs were shown to minimize incidence of DM. Large epidemiological studies that investigated the effect of SVR on CVD showed great discrepancies in terms of results, with predominant findings indicating that CVD events decreased in patients with SVR compared to non-responders or untreated ones. In this review, we present a summary of the current knowledge regarding extrahepatic sequelae of CHC following SVR, which may have an impact on healthcare providers' clinical practice.


Assuntos
Hepacivirus , Hepatite C Crônica , Antivirais/uso terapêutico , Genótipo , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferons/uso terapêutico , Resposta Viral Sustentada
3.
World J Gastroenterol ; 27(14): 1369-1391, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33911462

RESUMO

Infection with the hepatitis B virus (HBV) is still a major global health threat as 250 million people worldwide continue to be chronically infected with the virus. While patients may be treated with nucleoside/nucleotide analogues, this only suppresses HBV titre to sub-detection levels without eliminating the persistent HBV covalently closed circular DNA (cccDNA) genome. As a result, HBV infection cannot be cured, and the virus reactivates when conditions are favorable. Interferons (IFNs) are cytokines known to induce powerful antiviral mechanisms that clear viruses from infected cells. They have been shown to induce cccDNA clearance, but their use in the treatment of HBV infection is limited as HBV-targeting immune cells are exhausted and HBV has evolved multiple mechanisms to evade and suppress IFN signalling. Thus, to fully utilize IFN-mediated intracellular mechanisms to effectively eliminate HBV, instead of direct IFN administration, novel strategies to sustain IFN-mediated anti-cccDNA and antiviral mechanisms need to be developed. This review will consolidate what is known about how IFNs act to achieve its intracellular antiviral effects and highlight the critical interferon-stimulated gene targets and effector mechanisms with potent anti-cccDNA functions. These include cccDNA degradation by APOBECs and cccDNA silencing and transcription repression by epigenetic modifications. In addition, the mechanisms that HBV employs to disrupt IFN signalling will be discussed. Drugs that have been developed or are in the pipeline for components of the IFN signalling pathway and HBV targets that detract IFN signalling mechanisms will also be identified and discussed for utility in the treatment of HBV infections. Together, these will provide useful insights into design strategies that specifically target cccDNA for the eradication of HBV.


Assuntos
Hepatite B Crônica , Hepatite B , Antivirais/farmacologia , Antivirais/uso terapêutico , DNA Circular , DNA Viral/genética , DNA Viral/uso terapêutico , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Interferons/uso terapêutico , Replicação Viral
4.
Cells ; 10(3)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806810

RESUMO

As highlighted by the COVID-19 global pandemic, elderly individuals comprise the majority of cases of severe viral infection outcomes and death. A combined inability to control viral replication and exacerbated inflammatory immune activation in elderly patients causes irreparable immune-mediated tissue pathology in response to infection. Key to these responses are type I, II, and III interferons (IFNs), which are involved in inducing an antiviral response, as well as controlling and suppressing inflammation and immunopathology. IFNs support monocyte/macrophage-stimulated immune responses that clear infection and promote their immunosuppressive functions that prevent excess inflammation and immune-mediated pathology. The timing and magnitude of IFN responses to infection are critical towards their immunoregulatory functions and ability to prevent immunopathology. Aging is associated with multiple defects in the ability of macrophages and dendritic cells to produce IFNs in response to viral infection, leading to a dysregulation of inflammatory immune responses. Understanding the implications of aging on IFN-regulated inflammation will give critical insights on how to treat and prevent severe infection in vulnerable individuals. In this review, we describe the causes of impaired IFN production in aging, and the evidence to suggest that these impairments impact the regulation of the innate and adaptive immune response to infection, thereby causing disease pathology.


Assuntos
Imunidade Adaptativa , Envelhecimento/imunologia , Imunidade Inata , Interferons/fisiologia , Replicação Viral/imunologia , Idoso , /virologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interferon Tipo I/imunologia , Interferon Tipo I/uso terapêutico , Interferon gama/imunologia , Interferon gama/uso terapêutico , Interferons/imunologia , Interferons/uso terapêutico
5.
Clin Microbiol Rev ; 34(3)2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-33789928

RESUMO

Several viruses target the human respiratory tract, causing different clinical manifestations spanning from mild upper airway involvement to life-threatening acute respiratory distress syndrome (ARDS). As dramatically evident in the ongoing SARS-CoV-2 pandemic, the clinical picture is not always easily predictable due to the combined effect of direct viral and indirect patient-specific immune-mediated damage. In this review, we discuss the main RNA (orthomyxoviruses, paramyxoviruses, and coronaviruses) and DNA (adenoviruses, herpesviruses, and bocaviruses) viruses with respiratory tropism and their mechanisms of direct and indirect cell damage. We analyze the thin line existing between a protective immune response, capable of limiting viral replication, and an unbalanced, dysregulated immune activation often leading to the most severe complication. Our comprehension of the molecular mechanisms involved is increasing and this should pave the way for the development and clinical use of new tailored immune-based antiviral strategies.


Assuntos
Vírus de DNA , Lesão Pulmonar , Vírus de RNA , Infecções Respiratórias , Viroses , Adulto , Idoso , Antivirais/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Lactente , Recém-Nascido , Interferons/uso terapêutico , Pulmão/imunologia , Pulmão/virologia , Lesão Pulmonar/diagnóstico , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/imunologia , Lesão Pulmonar/virologia , Masculino , Pessoa de Meia-Idade , Pandemias
6.
Vet J ; 271: 105648, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33840487

RESUMO

Interferons (IFNs) are cytokines that play an important role in the immune response of animals and humans. A number of studies reviewed here have evaluated the use of human, canine and feline IFNs as treatments for infectious, inflammatory and neoplastic disease in dogs and cats. Recombinant canine IFN-γ is deemed an efficacious therapy for canine atopic dermatitis. Recombinant feline IFN-ω is effective against canine parvoviral enteritis and has also been recommended for canine atopic dermatitis. Based on limited evidence, recombinant canine IFN-α could be a topical treatment option for dogs with gingivitis and keratoconjunctivitis sicca. Conclusive evidence is lacking for other diseases and large randomised controlled trials are needed before IFNs can be recommended for other indications.


Assuntos
Doenças do Gato/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Interferons/uso terapêutico , Animais , Gatos , Cães , Gengivite/tratamento farmacológico , Humanos , Infecções/tratamento farmacológico , Infecções/veterinária , Inflamação/tratamento farmacológico , Inflamação/veterinária , Interferon-alfa/uso terapêutico , Ceratoconjuntivite Seca/tratamento farmacológico , Ceratoconjuntivite Seca/veterinária , Neoplasias/tratamento farmacológico , Neoplasias/veterinária , Proteínas Recombinantes/uso terapêutico , Viroses/tratamento farmacológico , Viroses/veterinária
8.
Inflamm Res ; 70(4): 389-405, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33608746

RESUMO

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a world-wide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, treatment of severe COVID-19 is far from clear. Therefore, it is urgent to develop an effective option for the treatment of patients with COVID-19. Most patients with severe COVID-19 exhibit markedly increased serum levels of pro-inflammatory cytokines, including interferon (IFN)-α, IFN-γ, and interleukin (IL)-1ß. Immunotherapeutic strategies have an important role in the suppression of cytokine storm and respiratory failure in patients with COVID-19. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar preprint database using all available MeSH terms for Coronavirus, SARS-CoV-2, anti-rheumatoid agents, COVID-19, cytokine storm, immunotherapeutic drugs, IFN, interleukin, JAK/STAT inhibitors, MCP, MIP, TNF. RESULTS: Here, we first review common complications of COVID-19 patients, particularly neurological symptoms. We next explain host immune responses against COVID-19 particles. Finally, we summarize the existing experimental and clinical immunotherapeutic strategies, particularly anti-rheumatoid agents and also plasma (with a high level of gamma globulin) therapy for severe COVID-19 patients. We discuss both their therapeutic effects and side effects that should be taken into consideration for their clinical application. CONCLUSION: It is suggested that immunosuppressants, such as anti-rheumatoid drugs, could be considered as a potential approach for the treatment of cytokine storm in severe cases of COVID-19. One possible limitation of immunosuppressant therapy is their inhibitory effects on host anti-viral immune response. So, the appropriate timing of administration should be carefully considered.


Assuntos
/epidemiologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Animais , Antirreumáticos/uso terapêutico , Citocinas/metabolismo , Inibidores Enzimáticos/uso terapêutico , Humanos , Imunização Passiva , Imunossupressores/uso terapêutico , Imunoterapia , Inflamação/tratamento farmacológico , Interferons/uso terapêutico , Interleucina-1/antagonistas & inibidores , Interleucina-6/antagonistas & inibidores , Janus Quinase 1/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Insuficiência Respiratória/terapia , Fator de Transcrição STAT1/antagonistas & inibidores , Transdução de Sinais
9.
Food Chem Toxicol ; 150: 112087, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33640537

RESUMO

Coronavirus disease-19 (COVID-19) is a complex disease that causes illness ranging from mild to severe respiratory problems. It is caused by a novel coronavirus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) that is an enveloped positive-sense single-stranded RNA (+ssRNA) virus belongs to coronavirus CoV family. It has a fast-spreading potential worldwide, which leads to high mortality regardless of lows death rates. Now some vaccines or a specific drug are approved but not available for every country for disease prevention and/or treatment. Therefore, it is a high demand to identify the known drugs and test them as a possible therapeutic approach. In this critical situation, one or more of these drugs may represent the only option to treat or reduce the severity of the disease, until some specific drugs or vaccines will be developed and/or approved for everyone in this pandemic. In this updated review, the available repurpose immunotherapeutic treatment strategies are highlighted, elucidating the crosstalk between the immune system and SARS-CoV-2. Despite the reasonable data availability, the effectiveness and safety of these drugs against SARS-CoV-2 needs further studies and validations aiming for a better clinical outcome.


Assuntos
Antivirais/farmacologia , Inflamação/etiologia , /efeitos dos fármacos , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , /imunologia , Citocinas/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interferons/farmacologia , Interferons/uso terapêutico , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , /imunologia
10.
Ann Palliat Med ; 10(1): 707-720, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33440983

RESUMO

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.


Assuntos
Antivirais/uso terapêutico , /terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/farmacologia , Alanina/uso terapêutico , Amidas/farmacologia , Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Azetidinas/farmacologia , Azetidinas/uso terapêutico , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Combinação de Medicamentos , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/farmacologia , Indóis/uso terapêutico , Interferons/farmacologia , Interferons/uso terapêutico , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Lopinavir/farmacologia , Lopinavir/uso terapêutico , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Purinas/farmacologia , Purinas/uso terapêutico , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Ritonavir/farmacologia , Ritonavir/uso terapêutico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Tiazóis/farmacologia , Tiazóis/uso terapêutico
11.
Ann Neurol ; 89(4): 780-789, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33480077

RESUMO

OBJECTIVE: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). METHODS: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. RESULTS: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. INTERPRETATION: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021;89:780-789.


Assuntos
/fisiopatologia , Hospitalização/estatística & dados numéricos , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , /mortalidade , Fumarato de Dimetilo/uso terapêutico , Feminino , Cloridrato de Fingolimode/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Unidades de Terapia Intensiva/estatística & dados numéricos , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mortalidade , Esclerose Múltipla/complicações , Natalizumab/uso terapêutico , Índice de Gravidade de Doença , Adulto Jovem
14.
PLoS Negl Trop Dis ; 14(12): e0008931, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33326423

RESUMO

BACKGROUND: Despite direct-acting antivirals (DAA), aims to "eradicate" viral hepatitis by 2030 remain unlikely. In Nepal, an expert consortium was established to treat HCV through Nepal earthquakes aftermath offering a model for HCV treatment expansion in a resource-poor setting. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, we established a network of hepatologists, laboratory experts, and community-based leaders at 6 Opioid Substitution Treatment (OST) sites from 4 cities in Nepal screening 838 patients for a treatment cohort of 600 individuals with HCV infection and past or current drug use. During phase 1, patients were treated with interferon-based regimens (n = 46). During phase 2, 135 patients with optimal predictors (HIV controlled, without cirrhosis, low baseline HCV viral load) were treated with DAA-based regimens. During phase 3, IFN-free DAA treatment was expanded, regardless of HCV disease severity, HIV viremia or drug use. Sustained virologic response (SVR) was assessed at 12 weeks. Median age was 37 years and 95.5% were males. HCV genotype was 3 (53.2%) or 1a (40.7%) and 32% had cirrhosis; 42.5% were HIV-HCV coinfected. The intention-to-treat (ITT) SVR rates in phase 2 and 3 were 97% and 81%, respectively. The overall per-protocol and ITT SVR rates were 97% and 85%, respectively. By multivariable analysis, treatment at the Kathmandu site was protective and substance use, treatment during phase 3 were associated with failure to achieve SVR. CONCLUSIONS/SIGNIFICANCE: Very high SVR rates may be achieved in a difficult-to-treat, low-income population whatever the patient's profile and disease severity. The excellent treatment outcomes observed in this real-life community study should prompt further HCV treatment initiatives in Nepal.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Interferons/uso terapêutico , Cirrose Hepática/complicações , Adulto , Coinfecção , Quimioterapia Combinada , Feminino , Hepatite C/complicações , Hepatite C/virologia , Humanos , Cirrose Hepática/virologia , Masculino , Nepal , Resposta Viral Sustentada , Resultado do Tratamento
15.
Adv Chronic Kidney Dis ; 27(5): 434-441, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33308510

RESUMO

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Insuficiência Renal Crônica/metabolismo , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , /prevenção & controle , /uso terapêutico , Cloroquina/uso terapêutico , Creatinina/metabolismo , Citidina/análogos & derivados , Citidina/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Interações Medicamentosas , Humanos , Hidroxicloroquina/uso terapêutico , Hidroxilaminas/uso terapêutico , Imunização Passiva , Interferons/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Lopinavir/uso terapêutico , Pirazinas/uso terapêutico , Eliminação Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Terapia de Substituição Renal , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico
16.
Rev. cuba. med. trop ; 72(3): e584, sept.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1156537

RESUMO

Introducción: En pacientes infectados con el virus de la hepatitis C se demostró que los polimorfismos de un simple nucleótido del gen de la interleucina 10 (IL10), influyen en la respuesta virológica sostenida al tratamiento con interferón y ribavirina, y en la inmunopatogénesis de la enfermedad. Objetivo: Determinar la frecuencia de los polimorfismos de un simple nucleótido de la región promotora del gen de la interleucina 10, según respuesta virológica sostenida y grado de lesión hepática. Métodos: Se realizó un estudio descriptivo, de corte transversal y se determinó la carga del virus de la hepatitis C por RT-PCR en tiempo real. Se estudiaron 25 pacientes cubanos con virus de inmunodeficiencia humana coinfectados con VHC, 24 semanas después del tratamiento con interferón y ribavirina. Para evaluar la variabilidad genética de la interleucina 10, los polimorfismos de un simple nucleótido se identificaron por secuenciación nucleotídica, -592 (A>C) y -819 (T>C). El grado de fibrosis hepática se calculó por el índice aspartato aminotransferasa/plaquetas. Resultados: El 44,0 por ciento (11/25) de los pacientes lograron respuesta virológica sostenida, y en el 56,0 por ciento (14/25) restante no se obtuvo esta. En los individuos en que se dio la respuesta predominaron los genotipos bajos productores de la interleucina 10, -592AA (36,3 por ciento vs. 21,4 por ciento) y -819TT (54,5 por ciento vs. 21,4 por ciento). En estos casos, el análisis de la frecuencia alélica mostró mayor frecuencia del alelo T para el SNP -819 (p= 0,0470). El índice aspartato aminotransferasa/plaquetas fue compatible con fibrosis hepática sin cirrosis en pacientes sin respuesta virológica sostenida, mientras que en los coinfectados que tuvieron respuesta indicó ausencia de lesión hepática. Conclusiones: Los resultados sugieren que las variantes de los polimorfismos de un simple nucleótido del gen de la interleucina 10 evaluados, podrían estar relacionados con la respuesta virológica sostenida y la patogénesis de la hepatitis C en los pacientes estudiados(AU)


Introduction: The study of patients infected with hepatitis C virus revealed that polymorphisms of a single nucleotide of the interleukin-10 (IL10) gene influence the sustained virological response to the treatment with interferon and ribavirin, and the immunopathogenesis of the disease. Objective: Determine the frequency of single-nucleotide polymorphisms from the interleukin-10 gene promoter region according to the sustained virological response and the degree of liver injury. Methods: A descriptive cross-sectional study was conducted and hepatitis C viral load was determined by RT-PCR. A sample of 25 Cuban HIV/HCV coinfected patients were studied 24 weeks after treatment with interferon and ribavirin. To evaluate the genetic variability of interleukin 10, the single-nucleotide polymorphisms were identified by nucleotide sequencing, -592 (A>C) and -819 (T>C). The degree of liver fibrosis was estimated by the aspartate aminotransferase / platelet index. Results: Of the patients studied, 44.0 percent (11/25) achieved a sustained virological response and 56.0 percent (14/25) did not. In individuals displaying the response, a predominance was found of low interleukin-10 producing genotypes, -592AA (36.3 percent vs. 21.4 percent) and -819TT (54.5 percent vs. 21.4 percent). In those cases, allele frequency analysis showed a greater allele T frequency for SNP -819 (p= 0.0470). The aspartate aminotransferase / platelet index was compatible with kidney fibrosis without cirrhosis in patients without a sustained virological response, and indicated an absence of liver injury in coinfected patients displaying a response. Conclusions: Results suggest that the variants evaluated of single-nucleotide polymorphisms of the interleukin-10 gene could be related to the sustained virological response and the pathogenesis of hepatitis C in the patients studied(AU)


Assuntos
Humanos , HIV , Interferons/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Subunidade beta de Receptor de Interleucina-10 , Resposta Viral Sustentada , Epidemiologia Descritiva , Estudos Transversais
17.
Viruses ; 12(12)2020 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-33322160

RESUMO

Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID-19 may elicit an autonomous antiviral state, restrict the virus infection, and prevent COVID-19 progression. Inborn genetic flaws and autoreactive antibodies that block IFN response have been significantly associated with about 14% of patients with life-threatening COVID-19 pneumonia. In most severe COVID-19 patients without genetic errors in IFN-relevant gene loci, IFN dysregulation is progressively worsened and associated with the situation of pro-inflammation and immunopathy, which is prone to autoimmunity. In addition, the high correlation of severe COVID-19 with seniority, males, and individuals with pre-existing comorbidities will be plausibly explained by the coincidence of IFN aberrance in these situations. Collectively, current studies call for a better understanding of the IFN response regarding the spatiotemporal determination and subtype-specificity against SARS-CoV-2 infections, which are warranted to devise IFN-related prophylactics and therapies.


Assuntos
Antivirais/imunologia , Interferons/imunologia , /patogenicidade , Antivirais/uso terapêutico , /patologia , Progressão da Doença , Humanos , Interferons/deficiência , Interferons/uso terapêutico , Cinética , Prognóstico , Transdução de Sinais , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/patologia
18.
Eur Rev Med Pharmacol Sci ; 24(23): 12593-12608, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33336780

RESUMO

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , /tratamento farmacológico , /terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Antiparasitários/uso terapêutico , Canabinoides/uso terapêutico , Cloroquina/uso terapêutico , Inativadores do Complemento/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/uso terapêutico , Interferons/uso terapêutico , Ivermectina/uso terapêutico , Lopinavir/uso terapêutico , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico , Teicoplanina/uso terapêutico , Tetraciclinas/uso terapêutico , Tiazóis/uso terapêutico
19.
Int Immunopharmacol ; 88: 106924, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32877828

RESUMO

COVID-19, the disease induced by the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has imposed an unpredictable burden on the world. Drug repurposing has been employed to rapidly find a cure; but despite great efforts, no drug or vaccine is presently available for treating or prevention of COVID-19. Apart from antivirals, immunotherapeutic strategies are suggested considering the role of the immune response as the host defense against the virus, and the fact that SARS-CoV-2 suppresses interferon induction as an immune evasion strategy. Active immunization through vaccines, interferon administration, passive immunotherapy by convalescent plasma or synthesized monoclonal and polyclonal antibodies, as well as immunomodulatory drugs, are different immunotherapeutic approaches that will be mentioned in this review. The focus would be on passive immunotherapeutic interventions. Interferons might be helpful in some stages. Vaccine development has been followed with unprecedented speed. Some of these vaccines have been advanced to human clinical trials. Convalescent plasma therapy is already practiced in many countries to help save the lives of severely ill patients. Different antibodies that target various steps of SARS-CoV-2 pathogenesis or the associated immune responses are also proposed. For treating the cytokine storm induced at a late stage of the disease in some patients, immune modulation through JAK inhibitors, corticosteroids, and some other cognate classes are evaluated. Given the changing pattern of cytokine induction and immune responses throughout the COVID-19 disease course, different adapted approaches are needed to help patients. Gaining more knowledge about the detailed pathogenesis of SARS-CoV-2, its interplay with the immune system, and viral-mediated responses are crucial to identify efficient preventive and therapeutic approaches. A systemic approach seems essential in this regard.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Imunoterapia/métodos , Pneumonia Viral/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/sangue , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Humanos , Imunização Passiva , Interferons/administração & dosagem , Interferons/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Resultado do Tratamento , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia
20.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...