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1.
BMJ Case Rep ; 13(12)2020 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-33334760

RESUMEN

We present the case of a 39-year-old man with epigastric pain, nausea and vomiting. The patient scored 4 in the Visual Triage Checklist of acute respiratory symptoms; a COVID-19 swab was taken. Prompt review of the peripheral blood smear showed evidence of microangiopathic haemolytic anaemia and thrombocytopenia. Because the patient had a picture of thrombotic thrombocytopenic purpura, plasma exchange and corticosteroids were started immediately. After 3 days, he developed severe ischaemic stroke and his swabs came back positive for COVID-19 by reverse transcription PCR. Therefore, triple therapy was started (lopinavir/ritonavir, ribavirin and interferon beta-1b). White blood cell count reached 50×109/L (normal range, 4.5-11×109/L), mainly neutrophils. All the workup for autoimmune diseases was negative. The patient showed delayed improvement in lactate dehydrogenase, haemoglobin and platelet count until we increased the volume of plasma exchange and subsided the inflammatory response of COVID-19. After that, the patient showed an excellent recovery.


Asunto(s)
/diagnóstico , Púrpura Trombocitopénica Trombótica/diagnóstico , Adulto , /tratamiento farmacológico , Combinación de Medicamentos , Humanos , Interferón beta/uso terapéutico , Lopinavir/uso terapéutico , Masculino , Intercambio Plasmático/métodos , Púrpura Trombocitopénica Trombótica/etiología , Ritonavir/uso terapéutico
2.
Curr Opin HIV AIDS ; 15(6): 336-340, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33002954

RESUMEN

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is a highly contagious and potentially lethal pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No specific antiviral treatment is currently available. The purpose of this review is to highlight the main repurposed drug treatments with in-vitro or in-vivo efficacy against the SARS-CoV-2. RECENT FINDINGS: Recent clinical trials suggested remdesivir, IFN-ß-1b and favipiravir have potential clinical and/or virological benefits on patients with COVID-19. Short course of stress dose of corticosteroids might be used as adjunctive treatment to patients who are late presenters with cytokine storm. Convalescent plasma from recovered COVID-19 patients with high neutralizing antibody might also be beneficial in the treatment of severe disease. SUMMARY: Early effective antiviral therapy in COVID-19 patients will suppress the SARS-CoV-2 viral load. Adjunctive therapy with corticosteroid and convalescent plasma might further ameliorate the cytokine response. Further randomized clinical trials of combination therapy are needed.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Antivirales/uso terapéutico , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/terapia , Humanos , Inmunización Pasiva , Interferón beta/uso terapéutico , Pandemias , Neumonía Viral/inmunología
3.
Buenos Aires; IECS; 13 oct. 2020.
No convencional en Español | LILACS, BRISA/RedTESA | ID: biblio-1140945

RESUMEN

CONTEXTO CLÍNICO: La Enfermedad por el Coronavirus 2019 (COVID­19, por su sigla en inglés Coronavirus Disease 2019) es una enfermedad respiratoria de humanos producida por un nuevo coronavirus identificado con la sigla SARS-CoV-2. El 11 de marzo de 2020 la Organización Mundial de la Salud (OMS) declaro la COVID-19 como uma pandemia. Desde ese momento hasta este octubre 2020 su circulación se ha reportado en 205 países reportándose más de 36 millones de casos y más de un millón de muertes. El período de incubación de la infección por 2019­nCoV es de 2 a 14 días. La mayor parte de los contagios se producen persona a persona, siendo altamente transmisible. La clínica varía desde casos asintomáticos a cuadros febriles con tos y dificultad respiratoria, neumonía y distrés respiratorio. También puede acompañarse de alteraciones gastrointestinales.2 En los casos con mal pronóstico, el paciente presenta un importante deterioro respiratorio en 4-8 días. Las imágenes radiológicas muestran generalmente neumonía focal o generalizada semejante al síndrome de distress respiratório agudo. La mayoría de los casos graves requieren ingreso hospitalario, siendo mayoritariamente casos primarios en pacientes de edad avanzada y con comorbilidades (diabetes, enfermedad crónica renal, hipertensión, enfermedad cardiaca y enfermedad pulmonar crónica). La tasa media de letalidad de los pacientes ingresados a UTI es cercana al 49%, siendo los valores más elevados en pacientes masculinos de más de 50 años con comorbilidades múltiples. Actualmente el tratamiento de la COVID­19 es sintomático y de sostén no existiendo hasta el momento tratamiento farmacológico específico curativo. Los tratamientos que se han propuestos son: inhibidores de la ARN polimerasa dependiente de ARN (remdesivir, favipiramir), inhibidores de la neuraminidasa (oseltamivir), inhibidores de la protease (lopinavir/ritonavir, desulfura, inhibidores de la enzima convertidora de angiotensina 2, inhibidores de quinasa (imatinib, baricitinib, ribavirin), inmunomoduladores (plasma de convaleciente, anticuerpos ante receptores IL-6 como tocilizumab y otros, dentro de los cuales se incluye el interferón, los glucorticoides y el umifenovir. En otras pandemias con virus SARS y MERS se ha usado el interferón, dado que múltiples estudios in vitro demuestran acción antiviral. Estudios in vitro específicos en el estudio del virus SARS-CoV-2 definen que la cinética del interferón podría ser variable en los distintos grados de enfermedad y sobre todo en la definición que cuando comenzar su uso, dado el desconocimiento de las curvas virales del SARS-CoV-2 y ventanas terapéuticas apropriadas. El uso asociado de interferón con otros antivirales surge de los experiencia de algún beneficio en estúdios realizados en el tratamiento de los virus MERS-CoV. Dada la falta de vacunas o tratamentos específicos para el nuevo coronavirus SARS-CoV-2, se postula el uso de interferón para el tratamento de pacientes COVID-19 positivos. TECNOLOGÍA: Los distintos tipos de Interferones (IFN) tienen acciones inmunomoduladoras y antivirales uniéndose a receptores celulares, realizando procesos transcripcionales que activan elsistema de citoquinas ante infecciones virales. Los IFN se clasifican en tipo I, II y III. Los IFN tipo I (IFN-α y IFN-ß) son los que tienen mayor actividad antiviral. Los IFN producen expresión de genes que estimulan el estado antiviral celular. Este mecanismo es el que los propuso para los ensayos clinicos en los virus MERS-CoV y SARS-CoV. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de interferón beta en infección por COVID-19. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y recomendaciones de diferentes organizaciones de salud. CONCLUSIONES: No se ha encontrado evidencia del uso de interferón como mono droga para el tratamiento de pacientes con infección por COVID-19. Evidencia de muy baja calidad proveniente de un ensayo clínico de pocos pacientes y varios sesgos que evaluó el uso de interferón asociado a otros antivirales (lopinavir-ritonavir o atazanavir-ritonavir) en comparación con cualquiera de estas asociaciones, no ha demostrado una reducción de la mortalidad ni mejora clínica a los 28 días en pacientes con neumopatía severa sintomática por COVID-19. Ninguna de las guías o protocolos gubernamentales relevados y/o de sociedades científicas americanas, latinoamericanas y europeas recomiendan el uso interferón como mono droga o uso combinado con otros antivirales. Solo está autorizado su uso en el contexto de investigación clínica. Algunos ensayos clínicos aleatorizados que evalúan la eficacia y seguridad de esta droga em pacientes con cuadros respiratorios por COVID-19 se encuentran en curso, por lo que podrían cambiar la evidencia actualmente disponible.


Asunto(s)
Humanos , Neumonía Viral/tratamiento farmacológico , Interferón beta/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Betacoronavirus/efectos de los fármacos , Evaluación de la Tecnología Biomédica , Análisis Costo-Beneficio
4.
PLoS One ; 15(9): e0238476, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32877451

RESUMEN

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). METHODS AND FINDINGS: We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; P<0,0001), in patients who developed comorbidities after starting treatment (i.e., rheumatoid arthritis-HR = 1.65; P<0,0001), those exclusive SUS patients (HR = 1.31; P<0,0001) and among patients using intramuscular interferon beta (IM ßINF-1a) (28% to 60% compared to the other three treatments; P<0,0001). Lower risk of treatment failure was found among patients treated with glatiramer. CONCLUSIONS: This retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Resultado del Tratamiento , Adyuvantes Inmunológicos/uso terapéutico , Adulto , Brasil/epidemiología , Estudios de Cohortes , Análisis Costo-Beneficio , Femenino , Acetato de Glatiramer/uso terapéutico , Humanos , Interferón beta/uso terapéutico , Estimación de Kaplan-Meier , Masculino , Esclerosis Múltiple/tratamiento farmacológico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
6.
Nat Rev Immunol ; 20(10): 585-586, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32788708
7.
Life Sci ; 259: 118233, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32781067

RESUMEN

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with unpredictable clinical outcome. As such, there is an urgent need to identify biomarkers that can predict the treatment response. Therefore, in an open-label, clinical, paraclinical and molecular prospective study, we assessed 50 interferon (IFN) treated MS patients for Rio Score (RS)/Modified Rio Score (MRS) and densitometric expression of the interferon-induced protein 35 (IFI35), a signal-protein with potential to be clinically relevant in the management of the disease. We found 4.92-fold upregulated IFI35 in IFN-treated MS group respect to healthy controls (p < .0001) and 2.31-fold respect to untreated MS group (p < .0001). Moreover, IFI35 expression profile correlated with RS and MRS rank values (r = -0.6018, p < .0001; r = -0.620, p < .0001), white matter volume (r = -0.5041; p = .0017) and cerebral lesion load (r = -0.5075; p = .0026). Finally, the main proportion of IFN-treated MS patients non-reaching the 65% threshold in IFI35 expression leaved the RS/MRS rank value 0 in a period ranging from 5 to 15 months (p < .0001) from the study entry; instead, all patients that reaching this threshold maintained the RS/MRS value 0 until the study end (p < .0001). In conclusion, the expression level of IFI35 in untreated MS patients highlights a correlation with neuroinflammation. Furthermore, IFI35 expression in IFN-treated MS patients shows a modular correlation between dosing regimes, which is predictive for long-term clinical outcome and drug efficacy.


Asunto(s)
Interferón beta/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular/sangre , Esclerosis Múltiple/sangre , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Biomarcadores Farmacológicos/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroinmunomodulación , Valor Predictivo de las Pruebas , Estudios Prospectivos , Transcriptoma
9.
Cytokine Growth Factor Rev ; 54: 43-50, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32665127

RESUMEN

Coronavirus disease 2019 (COVID-19) first emerged in late 2019 in China. At the time of writing, its causative agent SARS-CoV-2 has spread worldwide infecting over 9 million individuals and causing more than 460,000 deaths. In the absence of vaccines, we are facing the dramatic challenge of controlling COVID-19 pandemic. Among currently available drugs, type I Interferons (IFN-I) - mainly IFN-α and ß -represent ideal candidates given their direct and immune-mediated antiviral effects and the long record of clinical use. However, the best modalities of using these cytokines in SARS-CoV-2 infected patients is a matter of debate. Here, we discuss how we can exploit the current knowledge on IFN-I system to tailor the most promising dosing, timing and route of administration of IFN-I to the disease stage, with the final aim of making these cytokines a valuable therapeutic strategy in today's fight against COVID-19 pandemic.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/prevención & control , Interferón-alfa/uso terapéutico , Interferón beta/uso terapéutico , Pandemias/prevención & control , Neumonía Viral/prevención & control , Humanos , Inmunoterapia/métodos , Prevención Secundaria/métodos
10.
Brasília; s.n; 6 jul. 2020.
No convencional en Portugués | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117629

RESUMEN

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, referente 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 17 artigos.


Asunto(s)
Humanos , Neumonía Viral/tratamiento farmacológico , Infecciones por Coronavirus/tratamiento farmacológico , Betacoronavirus/efectos de los fármacos , Evaluación de la Tecnología Biomédica , gammaglobulinas/uso terapéutico , Inmunoglobulinas/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Vacunas/uso terapéutico , Cloroquina/uso terapéutico , Interferón beta/uso terapéutico , Aldehído Reductasa/antagonistas & inhibidores , Corticoesteroides/uso terapéutico , Azitromicina/uso terapéutico , Sulfato de Zinc/uso terapéutico , Ritonavir/uso terapéutico , Oseltamivir/uso terapéutico , Lopinavir/uso terapéutico , Hidroxicloroquina/uso terapéutico
11.
Mult Scler Relat Disord ; 42: 102196, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32480326

RESUMEN

BACKGROUND: The Coronavirus (COVID-19), (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) has been spreading worldwide since its first identification in China. It has been speculated that patients with comorbidities and elderly patients could be at high risk for the pandemic reasoned respiratory insufficiency and death. At first, it was thought that the patients who use immunmodulator therapy could be even at higher risks of disease complications. However, it has been also speculated about that using immunmodulators could be an advantage for the clinical prognosis. Therefore, several immunmodulators are currently being tested as potential treatment for COVID-19. METHODS: In this paper we report on a patient that has been treated with type 1 interferon for multiple sclerosis who developed COVID-19. RESULTS: Despite using immunmodulator, the symptoms of the patient at hospitalization were mild and he did not show elevated D-dimer, and there was no lymphopenia. He was discharged to home-quarantine with no symptoms. DISCUSSION: This report supports the idea of using type 1 interferon in the treatment could be effective in COVID-19 affected patients.


Asunto(s)
Infecciones por Coronavirus/fisiopatología , Factores Inmunológicos/uso terapéutico , Interferón beta/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Neumonía Viral/fisiopatología , Adulto , Antibacterianos/uso terapéutico , Antimaláricos/uso terapéutico , Azitromicina/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/tratamiento farmacológico , Tos/etiología , Humanos , Hidroxicloroquina/uso terapéutico , Tiempo de Internación , Masculino , Esclerosis Múltiple/complicaciones , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X
13.
Mult Scler Relat Disord ; 43: 102174, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32464584

RESUMEN

BACKGROUND: SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS. IMPLICATIONS: In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.


Asunto(s)
Betacoronavirus/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Inmunosupresores/uso terapéutico , Linfopenia/inmunología , Esclerosis Múltiple/terapia , Neumonía Viral/inmunología , Alemtuzumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Antivirales/inmunología , Cladribina/uso terapéutico , Crotonatos/uso terapéutico , Deprescripciones , Dimetilfumarato/uso terapéutico , Clorhidrato de Fingolimod/uso terapéutico , Acetato de Glatiramer/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Evasión Inmune/inmunología , Inmunidad Innata/inmunología , Factores Inmunológicos/uso terapéutico , Interferón beta/uso terapéutico , Macrófagos/inmunología , Monocitos/inmunología , Natalizumab/uso terapéutico , Pandemias , Toluidinas/uso terapéutico
14.
Neurology ; 94(22): e2373-e2383, 2020 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-32430312

RESUMEN

OBJECTIVE: Disease-modifying treatments (DMTs) are the gold standard for slowing disability progression in multiple sclerosis (MS), but their effects on cognitive impairment, a key symptom of the disease, are mostly unknown. We conducted a systematic review and meta-analysis to evaluate the differential effects of DMTs on cognitive test performance in relapsing-remitting MS (RRMS). METHODS: PubMed, Scopus, and Cochrane Library were searched for studies reporting longitudinal cognitive performance data related to all major DMTs. The standardized mean difference (Hedges g) between baseline and follow-up cognitive assessment was used as the main effect size measure. RESULTS: Forty-four studies, including 55 distinct MS patient samples, were found eligible for the systematic review. Twenty-five studies were related to platform therapies (mainly ß-interferon [n = 17] and glatiramer acetate [n = 4]), whereas 22 studies were related to escalation therapies (mainly natalizumab [n = 14] and fingolimod [n = 6]). Reported data were mostly confined to the cognitive domain processing speed. A meta-analysis including 41 studies and 7,131 patients revealed a small to moderate positive effect on cognitive test performance of DMTs in general (g = 0.27, 95% confidence interval [CI] = [0.21-0.33]), but no statistically significant differences between platform (g = 0.27, 95% CI = [0.18-0.35]) and escalation therapies (g = 0.28, 95% CI = [0.19-0.37]) or between any single DMT and ß-interferon. CONCLUSIONS: DMTs are effective in improving cognitive test performance in RRMS, but a treatment escalation mainly to amend cognition is not supported by the current evidence. Given the multitude of DMTs and their widespread use, the available data regarding differential treatment effects on cognitive impairment are remarkably scant. Clinical drug trials that use more extensive cognitive outcome measures are urgently needed.


Asunto(s)
Cognición/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Cognición/fisiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/psicología , Clorhidrato de Fingolimod/farmacología , Clorhidrato de Fingolimod/uso terapéutico , Acetato de Glatiramer/farmacología , Acetato de Glatiramer/uso terapéutico , Humanos , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Inmunosupresores/farmacología , Interferón beta/farmacología , Interferón beta/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Esclerosis Múltiple Recurrente-Remitente/psicología , Natalizumab/farmacología , Natalizumab/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos
15.
Drug Discov Ther ; 14(2): 67-72, 2020 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-32336723

RESUMEN

The virus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries and territories worldwide. It has been declared as pandemic by World Health Organization (WHO) and the whole world is suffering from corona virus disease 2019 (COVID-19). Currently, no treatment for SARS-CoV-2 are approved because of lack of evidence, but a number of clinical trials are in process and we are expecting fruitful results very soon. This review focuses on various approaches of treatment and few of the most recent clinical trials carried out in this field.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Coronavirus/terapia , Neumonía Viral/terapia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Amidas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Betacoronavirus , Cloroquina/uso terapéutico , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/tratamiento farmacológico , Darunavir/uso terapéutico , Combinación de Medicamentos , Humanos , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Indoles/uso terapéutico , Interferón-alfa/uso terapéutico , Interferón beta/uso terapéutico , Lopinavir/uso terapéutico , Pandemias , Pirazinas/uso terapéutico , Ritonavir/uso terapéutico
16.
Artículo en Inglés | MEDLINE | ID: mdl-32152082

RESUMEN

Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-ß) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-ß also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-ß against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Lopinavir/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Ritonavir/uso terapéutico , Adenosina Monofosfato/uso terapéutico , Alanina/uso terapéutico , Animales , Anticuerpos Monoclonales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/terapia , Combinación de Medicamentos , Humanos , Inmunización Pasiva , Interferón beta/uso terapéutico , Ratones Transgénicos , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Pandemias , Ribavirina/uso terapéutico , Virus del SRAS/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores
17.
Georgian Med News ; (298): 84-88, 2020 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-32141856

RESUMEN

About 30-40% of multiple sclerosis (MS) patients treated with interferon-beta (IFN-ß) develop neutralizing antibodies (NABs) to IFN-ß. NABs reduce bioavailability of IFN-ß, which leads to a decrease in the therapy effectiveness. The introduction of IFN-ß induce production of several proteins, which are used as markers of the therapy effectiveness. In this study, we assessed the prognostic significance of MS activity biomarkers in relation to the clinical data of MS patients treated with IFN-ß. The study involved 30 MS patients receiving IFN-ß. The average duration of therapy was 3.5 (3.4-5.3) years. The study showed the prevalence of NAbs formation in MS patients was 13% of cases, a year later - 30%. The level of viperin in patients without exacerbations during the observation period was lower than in patients with exacerbations. The study revealed the prognostic significance of viperin in relation to the frequency of exacerbations: viperin concentration above 0.2 ng / ml is a risk factor for exacerbation of MS. The results of this study suggest that viperin concentration in the serum could be used a prognostic marker in MS patients treated with interferons.


Asunto(s)
Interferón beta/farmacología , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/tratamiento farmacológico , Anticuerpos/análisis , Anticuerpos/sangre , Anticuerpos Neutralizantes , Biomarcadores/análisis , Biomarcadores/sangre , Georgia (República)/epidemiología , Humanos , Interferón beta/efectos adversos , Interferón beta/uso terapéutico , Esclerosis Múltiple/sangre , Esclerosis Múltiple/epidemiología , Prevalencia , Pronóstico , Resultado del Tratamiento
18.
Virology ; 541: 160-173, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32056714

RESUMEN

Unique among human viruses, Kaposi's sarcoma-associated herpesvirus (KSHV) encodes several homologs of cellular interferon regulatory factors (vIRFs). Since KSHV expresses multiple factors that can inhibit interferon (IFN) signaling to promote virus production, it is still unclear to what extent vIRFs contribute to these specific processes during KSHV infection. To study the function of vIRFs during viral infection, we engineered 3xFLAG-tagged-vIRF and vIRF-knockout recombinant KSHV clones, which were utilized to test vIRF expression, as well as their requirement for viral replication, virus production, and inhibition of the type I IFN pathway in different models of lytic KSHV infection. Our data show that all vIRFs can be expressed as lytic viral proteins, yet were dispensable for KSHV production and inhibition of type I IFN. Nevertheless, as vIRFs were able to suppress IFN-stimulated antiviral genes, vIRFs may still promote the KSHV lytic cycle in the presence of an ongoing antiviral response.


Asunto(s)
Herpesvirus Humano 8/fisiología , Factores Reguladores del Interferón/fisiología , Interferón Tipo I/antagonistas & inhibidores , Proteínas Virales/fisiología , Replicación Viral , Células Cultivadas , Humanos , Interferón Tipo I/biosíntesis , Interferón beta/genética , Interferón beta/uso terapéutico , Transducción de Señal/fisiología , Activación Viral
19.
J Gastroenterol Hepatol ; 35(8): 1426-1436, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31951295

RESUMEN

BACKGROUND AND AIM: Interferon-stimulated gene 20 (ISG20) is an interferon-inducible exonuclease that inhibits the replication of several RNA viruses. In patients with chronic hepatitis B, ISG20 expression is related to the interferon-α treatment response. However, the molecular mechanism of ISG20-mediated anti-hepatitis B virus (HBV) activity is unclear. METHODS: We have investigated the effect of ISG20 on antiviral activity to address that. The life cycle of HBV was analyzed by the ectopic expression of ISG20 in HepG2 and HepG2-NTCP cells. Finally, to provide physiological relevance of our study, the expression of ISG20 from chronic hepatitis B patients was examined. RESULTS: Interferon-stimulated gene 20 was mainly induced by interferon-ß and dramatically inhibited HBV replication. In addition, ISG20 decreased HBV gene expression and transcription. Although ISG20 inhibited HBV replication by reducing viral enhancer activity, the expression of transcription factors that bind the HBV enhancer was not affected. Particularly, ISG20 suppressed HBV enhancer activity by binding to the enhancer II and core promoter (EnhII/Cp) region. CONCLUSION: Our findings suggest that ISG20 exerts the anti-HBV activity by acting as a putative repressor binding to the HBV EnhII/Cp region.


Asunto(s)
Exorribonucleasas/genética , Exorribonucleasas/metabolismo , Expresión Génica , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/genética , Interferón-alfa/uso terapéutico , Interferón beta/uso terapéutico , Activación Viral/genética , Exorribonucleasas/fisiología , Células Hep G2 , Humanos , Interferón-alfa/farmacología , Interferón beta/farmacología , Regiones Promotoras Genéticas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Replicación Viral/genética
20.
Nat Commun ; 11(1): 222, 2020 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-31924756

RESUMEN

Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Infecciones por Coronavirus/tratamiento farmacológico , Interferón beta/uso terapéutico , Lopinavir/uso terapéutico , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Ritonavir/uso terapéutico , Adenosina Monofosfato/uso terapéutico , Alanina/uso terapéutico , Animales , Antivirales/uso terapéutico , Carboxilesterasa/genética , Infecciones por Coronavirus/patología , Combinación de Medicamentos , Desarrollo de Medicamentos , Femenino , Humanos , Lesión Pulmonar/patología , Masculino , Ratones , Ratones Noqueados , Carga Viral , Replicación Viral/efectos de los fármacos
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