Tratamientos y bioterapias para COVID-19 / Therapeutics and biotherapies for covid-19

INTRODUCCIÓN: Un nuevo brote de coronavirus surgió en 2019 en Wuhan, China, causando conmoción en el sistema sanitario de todo el mundo; el Comité Internacional de Taxonomía de Virus lo denominó SARS-CoV-2, agente causante de la enfermedad COVID-19.El espectro de gravedad de la enfermedad es muy amplio: la mayoría de los pacientes no presentan gravedad, pero otros pueden desarrollar neumonías, y la insuficiencia respiratoria aguda es la causa más frecuente de mortalidad. Objetivo: analizar y desarrollar las distintas alternativas terapéuticas aportadas por la Biotecnología para tratar los síntomas de aquellos pacientes con COVID-19. Metodología: se realizó una revisión de la bibliografía disponible, a partir de enero de 2020 en PubMed, acerca de los tratamientos que se encuentran aún en ensayos clínicos y aquellos que cuentan con aprobación bajo uso de emergencia para la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a políticas de salud establecidas para la terapéutica durante dicha pandemia. Resultados: este trabajo aborda las nuevas alternativas terapéuticas para COVID-19 derivadas de la Biotecnología, que se encuentran tanto en uso como en etapas de ensayos clínicos comprendidos dentro del segmento de los biofármacos y las bioterapias. Se incluye un breve resumen del estatus regulatorio de entidades de salud, el mecanismo de acción de dichas terapias y características generales de cada uno. Se incluyen novedosas bioterapias que se empezaron a implementar para afrontar la pandemia. Conclusiones: la pandemia de coronavirus está poniendo a prueba el sistema sanitario internacional, para brindar soluciones tanto desde el diagnóstico y prevención como para el tratamiento de la población a fin de disminuir la mortalidad. Esto incluyó, obviamente también, al área de la Biotecnología aplicada a la salud, que ha aportado en los tres aspectos mencionados; el presente trabajo se centra en las respuestas de tipo terapéutico que ha brindado y que están comercializadas o en fases clínicas. (AU)

INTRODUCTION: A new coronavirus outbreak emerged in 2019 in Wuhan, China, causing a shock to the healthcare system around the world; the International Committee on Taxonomy of Viruses named it SARS-CoV- 2, the infectious agent of the COVID-19 disease. The spectrum of severity of the disease is very wide, most patients are not serious, but others can develop pneumonia, with acute respiratory failure being the most frequent cause of mortality. Objective: to analyze and develop the different therapeutic alternatives provided by Biotechnology dedicated to Health, to treat the symptoms of those COVID-19 patients who require it, and thus reduce mortality.Methodology: a review of the available literature from January 2020 in PubMed of the treatments that are still in clinical trials and those that have been approved under emergency use for the disease COVID-19 was performed. Searches were also carried out through Google and Google Scholar for publications of Health organizations in reference to health policies established for therapeutics during the mentioned pandemic. Results: this work addresses the new therapeutic alternatives derived from Biotechnology, which are both in use and in stages of clinical trials, to treat patients who developed COVID-19 included within the segment of biopharmaceuticals and biotherapies. A brief summary of the regulatory status of health entities, the mechanism of action of said therapies and general characteristics of each one is included. Innovative biotherapies that began to be implemented to face the pandemic are included. Conclusions: The coronavirus pandemic has driven the international health system to the test, to provide solutions both from the diagnosis, prevention and treatment of the population to reduce the mortality of patients. This obviously also included the area of Biotechnology applied to health, which has contributed in the three aspects mentioned. The present work focuses on the therapeutic responses that it has provided and that are commercialized or in clinical phases. (AU)

Review Covid-19 (sars-cov-2) and medicinal plants ­ literature / Revisão Covid-19 (sars-cov-2) e plantas medicinais - literatura / Revisión Covid-19 (sars-cov-2) y plantas medicinales - bibliografía

In December 2019, a new coronavirus originating from the city of Wuhan in China started an epidemic that brought many countries into chaos and despair. SARS-CoV-2, as identified, gave rise to the severe acute respiratory syndrome called COVID-19. Its transmission happens through droplets of saliva, hand or contaminated surfaces. Since its discovery, COVID-19 has led many to death, therefore, researchers from around the world have joined efforts to develop strategies to contain the virus. In this race, drugs such as Chloroquine and Hydroxychloroquine have become possible options for showing an antiviral effect, however, studies contest their efficiency, generating uncertainties. Therefore, other alternatives have been investigated in this context, and the study of medicinal plants has been the target of research for the treatment of COVID-19 in search of bioactive natural products that can exert an antiviral action. The study aimed to analyze the published literature on COVID-19 (SARS-CoV-2) and its relationship with medicinal plants. Bibliographical survey. So far, no specific treatment against the disease has been found, only supportive, with drugs that aim to improve the individual's immune system and ensure that the virus does not replicate, for example, there are options such as chloroquine, hydroxychloroquine, remdesivir and convalescent plasma. On the other hand, studies have revealed that medicinal plants such as garlic, among others, showed efficiency in modulating proteins with a view to preventing viral replication and improving immunity against COVID-19. So far, there are no drugs that are completely safe and have been shown to have activity against the new coronavirus (SARS-CoV-2). However, medicinal plants can contribute to the development of specific therapies against SARS-CoV-2 in a safe and effective way.

Em dezembro de 2019, um novo coronavírus originário da cidade de Wuhan, na China, iniciou uma epidemia que levou muitos países ao caos e ao desespero. O SARS-CoV-2, conforme identificado, deu origem à síndrome respiratória aguda grave chamada COVID-19. Sua transmissão acontece através de gotículas de saliva, mãos ou superfícies contaminadas. Desde sua descoberta, o COVID-19 levou muitos à morte, por isso, pesquisadores de todo o mundo uniram esforços para desenvolver estratégias para conter o vírus. Nesta corrida, medicamentos como Cloroquina e Hidroxicloroquina tornaram-se opções possíveis por apresentarem efeito antiviral, porém, estudos contestam sua eficiência, gerando incertezas. Portanto, outras alternativas têm sido investigadas nesse contexto, e o estudo de plantas medicinais tem sido alvo de pesquisas para o tratamento da COVID- 19 em busca de produtos naturais bioativos que possam exercer ação antiviral. O estudo teve como objetivo analisar a literatura publicada sobre COVID-19 (SARS-CoV-2) e sua relação com plantas medicinais. Levantamento bibliográfico. Até o momento, não foi encontrado nenhum tratamento específico contra a doença, apenas de suporte, com medicamentos que visam melhorar o sistema imunológico do indivíduo e garantir que o vírus não se replique, por exemplo, há opções como cloroquina, hidroxicloroquina, remdesivir e convalescença plasma. Por outro lado, estudos revelaram que plantas medicinais como o alho, entre outras, mostraram eficiência na modulação de proteínas visando prevenir a replicação viral e melhorar a imunidade contra a COVID-19. Até o momento, não existem medicamentos completamente seguros e que tenham demonstrado atividade contra o novo coronavírus (SARS-CoV-2). No entanto, as plantas medicinais podem contribuir para o desenvolvimento de terapias específicas contra o SARS-CoV-2 de forma segura e eficaz.

En diciembre de 2019, un nuevo coronavirus originario de la ciudad de Wuhan, en China, inició una epidemia que sumió a muchos países en el caos y la desesperación. El SARS-CoV- 2, tal y como fue identificado, dio lugar al síndrome respiratorio agudo severo denominado COVID-19. Su transmisión se produce a través de gotitas de saliva, de las manos o de superficies contaminadas. Desde su descubrimiento, el COVID-19 ha llevado a muchos a la muerte, por lo que investigadores de todo el mundo han aunado esfuerzos para desarrollar estrategias de contención del virus. En esta carrera, fármacos como la Cloroquina y la Hidroxicloroquina se han convertido en posibles opciones por mostrar un efecto antiviral, sin embargo, los estudios refutan su eficacia, generando incertidumbres. Por lo tanto, otras alternativas han sido investigadas en este contexto, y el estudio de las plantas medicinales ha sido el objetivo de la investigación para el tratamiento de COVID-19 en busca de productos naturales bioactivos que puedan ejercer una acción antiviral. El estudio tuvo como objetivo analizar la literatura publicada sobre el COVID-19 (SARS-CoV-2) y su relación con las plantas medicinales. Estudio bibliográfico. Hasta el momento, no se ha encontrado un tratamiento específico contra la enfermedad, sólo de soporte, con fármacos que buscan mejorar el sistema inmunológico del individuo y asegurar que el virus no se replique, por ejemplo, existen opciones como la cloroquina, hidroxicloroquina, remdesivir y plasma convaleciente. Por otro lado, estudios han revelado que plantas medicinales como el ajo, entre otras, mostraron eficacia en la modulación de proteínas con vistas a impedir la replicación viral y mejorar la inmunidad contra el COVID-19. Hasta el momento, no existen medicamentos que sean completamente seguros y que hayan demostrado tener actividad contra el nuevo coronavirus (SARS-CoV-2). Sin embargo, las plantas medicinales pueden contribuir al desarrollo de terapias específicas contra el SARS-CoV-2 de forma segura y eficaz.

Therapeutics and COVID-19: living guideline - 16 September 2022

The WHO Therapeutics and COVID-19: living guideline contains the Organization's most up-to-date recommendations for the use of therapeutics in the treatment of COVID-19. The latest version of this living guideline is available in pdf format (via the 'Download' button) and via an online platform, and is updated regularly as new evidence emerges. This twelfth version of the WHO living guideline now contains 19 recommendations. This latest update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers and Janus kinase (JAK) inhibitors in patients with severe or critical COVID-19, and modifies previous recommendations for the neutralizing monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe COVID-19.

Experiencia en cirugía de condilomas anales en mayores de 15 años / Experience in anal condyloma surgery in patients older than 15 years

Resumen Objetivo: Describir la experiencia en cirugía electiva de condilomas anales en pacientes mayores de 15 años en un hospital terciario de la Región Metropolitana. Material y Método: Estudio observacional retrospectivo y descriptivo, en el cual se analizan las intervenciones quirúrgicas electivas realizadas entre 2008 a 2021. Resultados: Dentro del período analizado se obtuvo 165 cirugías de condilomas anales, lo que corresponde a 137 pacientes en total. El 85% de los pacientes son de sexo masculino, el 68% de los pacientes son VIH positivo, un 87% de los pacientes MSM (hombres que tienen sexo con otros hombres) son VIH positivo, el 34% de los pacientes tiene antecedente de ETS, el 46% de los pacientes recibió terapia tópica como tratamiento preoperatorio o posoperatorio. Un 25% de los pacientes presenta recidiva en su historia personal, un 21% de los pacientes presenta lesiones anales intraepiteliales de alto grado, un 6% presenta carcinoma escamoso infiltrante. No hubo mortalidad descrita. Discusión: El presente estudio, describe la experiencia en cirugía de condilomas de un hospital terciario de la Región Metropolitana de Chile, cuya población corresponde a un estrato socioeconómico medio y bajo. Se logra describir a la población que es intervenida de condilomas acuminados, además de sus resultados quirúrgicos precoces y a largo plazo. Conclusión: El presente estudio, presenta una población de 137 pacientes operados de condilomas anales, a partir de los hallazgos de la cirugía. Se cumple el objetivo del estudio de caracterizar en un período de 12 años los resultados quirúrgicos de dicha serie, algo no reportado previamente en la literatura chilena.

Objective: To describe the experience in elective surgery for anal condylomas in patients over 15 years of age in a tertiary hospital in the Metropolitan Region. Materials and Method: Retrospective and descriptive observational study about elective surgical interventions performed between 2008 to 2021. Results: Within the analyzed period, 165 anal warts surgeries were obtained, corresponding to 137 patients. 85% of the patients are male, 68% are HIV positive, 87% of the MSM patients are HIV positive, 34% of the patients have a history of STDs, 46% of the patients received topical therapy as preoperative or postoperative treatment. 25% present recurrence in their personal history, 21% present high-grade anal intraepithelial lesions, 6% present infiltrating squamous carcinoma. There was no reported mortality. Discussion: The present study describes the experience in condyloma surgery in a tertiary hospital in the Metropolitan Region of Chile, whose population corresponds to a medium and low socioeconomic stratum. It is possible to describe the population that undergoes surgery for this reason, in addition to its early and long-term surgical results. Conclusion: The present study presents a population of 137 patients operated on for anal condylomas, based on the findings of the surgery. The objective of the study to characterize the surgical results of this series over a 12-year period is fulfilled, something not previously reported in the Chilean literature.

Remdesivir para el tratamiento de pacientes con COVID-19: (3 de junio de 2022) / Remdesivir for the treatment of patients with COVID-19: (June 3, 2022)

INTRODUCCIÓN: El remdesivir fue evaluado originalmente en ensayos clínicos para abordar el brote de virus del ébola en 2014.(13) Con la demostración de que remdesivir poseía una amplia actividad contra otros virus de ARN, incluidos los coronavirus, múltiples grupos evaluaron su actividad antiviral in vitro como in vivo en otras indicaciones. Posteriormente, se confirmó su actividad antiviral contra los coronavirus zoonóticos MERS, así como los coronavirus humanos circulantes HCoV-OC43 y HCoV-229E, agentes causantes del resfriado común.(14) Recientemente, también ha demostrado su actividad in vitro frente al SARS-CoV-2.(15) En un modelo de macaco Rhesus con infección por SARS-CoV-2 donde el tratamiento con remdesivir se inició poco después de la inoculación, los animales tratados con este fármaco presentaron niveles de virus más bajos en los pulmones y menos daño pulmonar respecto a los animales de control. Aunque este modelo animal no representa la enfermedad grave observada en algunos pacientes con COVID-19, se tomaron estos hallazgos como una posibilidad biológica para iniciar estudios clínicos con este fármaco antiviral en pacientes con COVID-19. OBJETIVO: El objetivo del presente informe es evaluar parámetros de eficacia, seguridad, conveniencia y recomendaciones disponibles acerca del empleo de remdesivir para el tratamiento de pacientes con COVID-19 en Argentina. MÉTODOS: Efectos en la Salud: Teniendo en cuenta la velocidad con la que la información relacionada a la pandemia aparece y se modifica, se desarrolló un protocolo sustentado en proyectos que resume activamente la evidencia científica a medida que la misma se hace disponible. Con este fin se utilizó la plataforma L- ove de Epistemonikos https://app.iloveevidence.com/topics para identificar revisiones sistemáticas "vivas". Se seleccionaron aquellas con una calidad metodológica apropiada evaluada a través de la herramienta AMSTAR-2, y que a su vez llevaran un proceso de actualización frecuente. De cada una de las revisiones sistemáticas identificadas se extractaron los efectos de la intervención sobre los desenlaces priorizados como importantes o críticos y la certeza en dichos efectos. Para la priorización de los desenlaces se adoptó una perspectiva desde el paciente considerando sus potenciales preferencias. La selección se realizó por consenso entre los autores y supervisores del informe considerando los resultados de múltiples ejercicios de priorización publicados, realizados en el marco del desarrollo de distintas guías de práctica clínica. Implementación: Este dominio contempla dos subdominios: la existencia de barreras y facilitadores en nuestro contexto para la implementación de la tecnología evaluada no consideradas en los otros dominios analizados, y los costos comparativos en relación con otras intervenciones similares. Con el objetivo de emitir un juicio de valor sobre la magnitud de dichos costos, en pacientes hospitalizados se utilizó como comparador al tratamiento con dexametasona, que ha demostrado ser una intervención accesible y de beneficios importantes en el contexto analizado. Recomendaciones: Para la identificación de recomendaciones sustentadas en evidencia y actualizadas, se utilizó la plataforma COVID recmap. Se seleccionaron aquellas guías con rigor metodológico apropiado según la herramienta AGREE II (> 70%) y se incorporaron sus recomendaciones al informe. RESULTADOS: Se identificaron tres revisiones sistemáticas que cumplieron con los criterios de inclusión del presente informe y reportaron resultados: Las revisiones sistemáticas identificadas incluyeron 12 estudios aleatorizados para remdesivir en COVID19 que aleatorizaron un total de 9869 pacientes. Los resultados de 12 ECCA, incluyendo los resultados finales del ensayo SOLIDARITY, muestran que, en pacientes hospitalizados con COVID-19 y enfermedad de moderada a crítica, el remdesivir probablemente reduce la mortalidad y la necesidad de ventilación mecánica invasiva, y podría mejorar el tiempo de resolución de los síntomas. La certeza de la evidencia fue clasificada como moderada debido a la imprecisión. En pacientes con enfermedad leve de comienzo reciente, el remdesivir podría reducir las hospitalizaciones, pero la certeza de la evidencia es baja también por imprecisión. Adicionalmente, existe información sobre la efectividad in vitro de remdesivir frente a las diferentes variantes de SARS-CoV-2. Esta información se encuentra disponible en OpenData Portal, que condensa lo reportado por conjunto priorizado de publicaciones (preprints y artículos revisados por pares). resultados muestran que remdesivir podría tener una efectividad similar frente a las nuevas variantes del SARS-CoV-2, incluida Omicrón y subvariantes (B.1.1.529; BA.1.1; BA.1; BA.1 [+Q493K]; BA.2; B.1.1.529 [+F694Y] en comparación de las variantes predominantes al momento de realizarse los estudios. CONCLUSIONES: El cuerpo de la evidencia disponible, muestra que en pacientes con enfermedad leve o de reciente comienzo y factores de riesgo para progresión a enfermedad severa, remdesivir podría disminuir las hospitalizaciones y podría aumentar la velocidad para la mejoría clínica y resolución de los sintomas. Sin embargo, la magnitud de la reducción solo resulta importante (mayor a 1%) para pacientes sin esquema de vacunación completo o con riesgo de respuesta inmune inapropriada. En pacientes hospitalizados con enfermedad severa en cambio, el remdesivir probablemente reduce la mortalidad y la necesidad de ventilación mecánica invasiva y podría mejorar el tiempo de resolución de los síntomas, sin aumentar los eventos adversos sérios. A pesar que remdesivir se encuentra autorizado para su comercialización en Argentina, existen algunas situaciones que podrían constituir barreras para el acceso. La vía de administración endovenosa podría no ser aceptada en personas con enfermedad leve. Además, el costo del tratamiento es muy elevado y existe una extensa población objetivo para la aplicación de este tratamiento, que podrían constituir también barreras de acceso. Las guías sugieren el tratamiento con remdesivir condicionado a aquellos pacientes no graves con mayor riesgo de hospitalización. También sugieren en forma condicional utilizar remdesivir en pacientes hospitalizados que requieren oxígeno y recomiendan fuertemente no utilizar en adultos hospitalizados con COVID-19 que requieran ventilación no invasiva o invasiva. En el contexto de América Latina y el Caribe, se sugirió que cada país debe evaluar la decisión de su uso con base en los recursos disponibles, la factibilidad de su implementación, el acceso, los factores específicos del paciente (p. ej., la duración de los síntomas, el funcionamiento renal, las interacciones farmacológicas), la cobertura de vacunación y la forma de administración. También, es importante que se determine la capacidad de los servicios para poder administrar los medicamentos y considerar el tiempo adecuado para su uso.

Linfogranuloma venéreo genital en un hombre que tiene sexo con hombre: reporte de caso no importado en Chile / Lymphogranuloma venerous genital in men who have sex with men: a non-imported case report in Chile

Resumen El linfogranuloma venéreo (LGV) es una infección de transmisión sexual (ITS) causada por Chlamydia trachomatis. En los últimos años, ha emergido principalmente en hombres que tienen sexo con hombres (HSH). Es frecuente su asociación con otras ITS como el virus de inmunodeficiencia humana (VIH) y la sífilis. Si bien el compromiso genital es la forma de presentación clásica, el síndrome anorrectal constituye el principal cuadro clínico en la actualidad. Presentamos el caso de un HSH con infección por VIH en terapia anti-retroviral, herpes genital recurrente y sífilis latente tratada, sin viajes recientes al extranjero, con adenopatías inguinales fistulizadas a piel, asociada a una úlcera genital dolorosa, sin síntomas anorrectales ni sistémicos, refractario a múltiples tratamientos antibacterianos y antivirales. El estudio con RPC de secreción de la fístula fue positiva a C. trachomatis. Se trató con doxiciclina por seis semanas, con buena respuesta clínica, sin complicaciones.

Abstract Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis bacteria. In the past years, it has emerged as a relevant infectious agent, mainly affecting men who have sex with men (MSM), frequently associated with other sexually transmitted infections as human immunodeficiency virus (HIV) and syphilis. Even though genital lesions correspond to the classical presentation of LGV, nowadays anorectal syndrome is more frequently reported. We present a MSM patient, HIV infected, being treated with antiretroviral drugs, with a history of recurrent genital herpes, also recently treated for a syphilis in a latent stage. He had no recent trips. He referred inguinal fistulized enlarged lymph nodes, associated with a painful genital ulcer, he denied anorectal or systemic symptoms. He had been treated with multiple antibiotic and antiviral drugs, with no clinical response. Molecular studies from the content of the fistulized lymph node identified C. trachomatis. The patient received doxycycline for 6 weeks, showing good clinical response.

Eficacia y Seguridad de Molnupiravir para el tratamiento de COVID-19 / Efficacy and Safety of Molnupiravir for the treatment of COVID-19

ANTECEDENTES: Este informe se efectúa en atención a la solicitud de la Dirección General de Intervenciones Estratégicas de Salud Pública del Ministerio de Salud. El objetivo es sintetizar la evidencia científica publicada respecto a la eficacia y seguridad de Molnupiravir en el tratamiento de pacientes con COVID-19. La UNAGESP elaboró 2 notas técnicas previas, vinculadas a esta solicitud - SNT N° 08-2021: Eficacia y Seguridad de Molnupiravir para el tratamiento de COVID-19 de fecha 6 de setiembre de 2021 - SNT N° 002-2022: Eficacia y Seguridad de Molnupiravir para el tratamiento de COVID-19, actualización al 29 de diciembre de 2021, de fecha enero de 2022. El presente informe actualiza la información previamente señalada. MÉTODOS: Pregunta PICO abordada en este informe: En pacientes adultos con COVID-19 ¿la administración de Molnupiravir es eficaz y seguro en comparación a no administrarlo para el tratamiento de COVID-19? Criterios de elegibilidad: Los criterios de selección de los estudios fueron los siguientes: Revisiones sistemáticas de Ensayos clínicos aleatorizados (ECA) o ECA que reporten resultados para al menos uno de los desenlaces de interés. Idioma: inglés o español. Se excluyeron estudios preclínicos, series de casos, reportes de casos, reportes breves y cartas al editor. Métodos para la búsqueda e identificación de la evidencia: Para la identificación de las revisiones sistemáticas se efectuó una búsqueda manual en la plataforma de COVID-END, recuperándose dos revisiones sistemáticas vivas: a. Revisión sistemática del Consorcio COVID-NMA disponible en https://covidnma.com/living_data/index.php?treatment1=Molnupiravir&submit=Validate#comparisons_div actualizada al 25 de febrero de 2022(2). b. Revisión Rápida de la Organización Panamericana de la Salud (OPS)(3), versión del 22 de febrero de 2022(4), disponible en https://iris.paho.org/handle/10665.2/52719 RESULTADOS: El Molnupiravir es un profármaco con actividad antiviral contra el SARS-CoV-2 cuyo mecanismo de acción es conocido como catástrofe de error viral o mutagénesis letal, ya que produce una acumulación de errores en el genoma viral que conduce a la inhibición de la replicación. Molnupiravir se metaboliza al análogo de nucleósido de la citidina, NHC, que se distribuye en las células donde el NHC se fosforila para formar el ribonucleósido trifosfato farmacológicamente activo (NHC-TP) el cual se incorpora en el ARN del SARS-CoV-2 mediante la ARN polimerasa viral para ejercer el mecanismo de acción. El 23 de diciembre de 2021, la Administración de Alimentos y Medicamentos de los Estados Unidos (FDA, su sigla del inglés Food and Drug Administration), emitió la autorización de uso de emergencia del Molnupiravir para el tratamiento de la enfermedad por COVID-19 de leve a moderada en adultos con resultados positivos en las pruebas virales directas del SARS-CoV-2 y que tienen un alto riesgo de progresión a COVID-19 grave y para quienes las opciones alternativas de tratamiento para la COVID-19 aprobadas o autorizadas por la FDA no son accesibles o clínicamente adecuadas. La dosis autorizada es de 800 mg por vía oral cada 12 horas durante 5 días, que debe iniciarse tan pronto como sea posible luego del diagnóstico y dentro de los 5 días de la aparición de los síntomas. No está autorizado para su uso en pacientes menores de 18 años, para el inicio del tratamiento en pacientes que requieren hospitalización debido a la COVID-19, para usar durante más de 5 días consecutivos y para profilaxis previa o posterior a la exposición para la prevención de COVID-19. En el país, el uso del Molnupiravir cuenta con registro sanitario condicional. CONCLUSIONES: Molnupiravir es un profármaco con actividad antiviral contra el SARS-CoV-2. Ha sido autorizado por la FDA de Estados Unidos para el tratamiento de COVID-19 leve a moderado en adultos con enfermedad de reciente comienzo, quienes tienen un alto riesgo de progresión a COVID-19 grave y para quienes las opciones alternativas de tratamiento aprobadas o autorizadas por la FDA no son accesibles o clínicamente adecuadas. En el país, el uso del Molnupiravir cuenta con registro sanitario condicional. El objetivo del informe fue sintetizar la evidencia científica respecto a la eficacia y seguridad del molnupiravir en el tratamiento de pacientes con COVID-19. La evidencia en pacientes adultos no hospitalizados, no vacunados, con COVID-19 leve a moderado, tiempo de enfermedad ≤ 5 días y con factores de riesgo para progresión a enfermedad severa mostró lo siguiente: - Molnupiravir en comparación a no administrarlo probablemente tiene un efecto pequeño sobre la mortalidad por cualquier causa a los 28 días: 11 muertes menos por cada 1000 pacientes tratados, IC 95%: 13 menos a 6 menos; 3 ensayos clínicos aleatorizados (ECA), 1937 participantes; certeza moderada. - Molnupiravir probablemente reduce las hospitalizaciones o la muerte por cualquier causa a los 28 días en comparación a no administrarlo, aunque el tamaño del efecto podría ser importante o pequeño: 28 pacientes menos por cada 1000 tratados se hospitalizaron o murieron, IC 95%: 46 menos a 2 menos; 2 ECA, 1735 participantes, certeza moderada. - Molnupiravir podría no incrementar la incidencia de eventos adversos serios en comparación con No administrarlo: 23 pacientes menos por cada 1000 tratados, IC 95%: 39 menos a 3 más; 4 ECA, 1955 participantes; certeza baja. En pacientes hospitalizados, con COVID-19 moderado o severo, no vacunados y más de 5 días desde el inicio de síntomas, la administración de Molnupiravir podría incrementar la mortalidad por cualquier causa a los 28 días (certeza baja), no incrementaría la incidencia de eventos adversos y eventos adversos serios (certeza baja) y es incierto si tendría algún impacto en la progresión a ventilación mecánica (certeza muy baja). Hasta la fecha del informe no se identificaron resultados publicados sobre la eficacia o efectividad de Molnupiravir en pacientes con antecedente de vacunación contra COVID-19 o en un contexto de circulación de la variante omicrón. Estudios in vitro mostraron que la actividad antiviral de Molnupiravir se mantuvo frente a la variante Ómicron. En estudios in vivo, redujo la replicación viral en vías respiratorias superiores y en tejido pulmonar en modelos animales que simulaban una infección viral leve o con afectación pulmonar no severa respectivamente.

Meningoencefalitis por virus Varicella-Zóster posterior a infección por SARS-CoV2: Reporte de dos casos / Meningoencephalitis caused by Varicella-Zoster virus after SARS-CoV2 infection: Two cases report

RESUMEN La meningoencefalitis por el VZV es una patología poco frecuente que se presenta con la reactivación del virus dentro del organismo. OBJETIVO: Describir la presentación clínica de dos pacientes con neuroinfección por VZV posteriormente a infección por SARS-CoV-2. REPORTE DEL CASO: El primer caso corresponde a un hombre de 59 años con antecedente de neumonía moderada por SARS-CoV-2 que después cursó con meningoencefalitis por VZV y, además, desarrolló un síndrome de Ramsay Hunt. El segundo caso es el de una mujer de 37 años con antecedente de infección leve por SARS CoV-2 con un cuadro de cefalea con signos de alarma, en quien se documentó neuroinfección por VZV

ABSTRACT Meningoencephalitis caused by varicella zoster virus is a rare pathology that presents due to the reactivation of the virus in the organism OBJECTIVE: To describe the clinical presentation of two patients with VZV neuroinfection presented after a SARS CoV-2 infection. CASE REPORT: The first case is a 59 year old male with previous moderate SARS CoV-2 infection who presented meningoencephalitis and was diagnosed with Ramsay Hunt's Syndrome. The second case is a 37 year old female with previous SARS CoV-2 infection who presented with an acute onset headache and was documented with VZV neuroinfection.

Molusco contagioso: actualización y casos clínicos / Molluscum contagiosum: an update and clinical cases

El molusco contagioso es una patología viral benigna muy frecuente, exclusiva del ser humano, y causada por un virus no clasificado del grupo de los Poxvirus. Las manifestaciones clínicas de la enfermedad inclu-yen lesiones en la piel, que pueden variar desde una pequeña pápula a un nódulo de mayor tamaño, pre-sentándose en forma solitaria o múltiple, dependien-do del estado inmunitario del paciente y del tiempo de evolución del proceso morboso. El estudio histo-patológico es importante para el diagnóstico, aunque en numerosas ocasiones éste se define clínicamen-te. Además del patrón histológico tradicional, y más frecuente, que exhibe hiperplasia e hipertrofia de la epidermis, se han descripto variantes poco usuales, cuyas características dependen, entre otros factores, de la sobreinfección y de la respuesta inmunitaria del paciente. En este trabajo se describen los rasgos ge-nerales del molusco contagioso y luego se presentan varios casos clínicos, uno de los cuales exhibe ma-nifestación inusual en la semimucosa del labio. Por último, se realizan comentarios referentes a la im-portancia que tiene para el odontólogo conocer esta patología y estar capacitado para detectarla, de modo de evitar sus complicaciones y su diseminación (AU)

Molluscum contagiosum is a very common benign viral pathologythat affects exclusively humans and is caused by an unclassified virus of the Poxvirus family. Clinical manifestations include skin lesions such as papule or nodule, which may range from a small papule to a larger nodule, presenting either solitary or multiple, depending on the immune status of the patient and the time of evolution of the morbid process. Histopathological study is important for the diagnosis, although in numerous occasions it is defined clinically. Classical and more frequent histology pattern exhibits hyperplasia and hypertrophy of the epidermis; however, distinct characteristics may occur depending on factors like superinfection and immune response of patients. This article describes general aspects of molluscum contagiosum and exposes several clinical cases, one of which exhibits an unusual manifestation in the semimucosa of the lip. Finally, comments are made regarding the importance for dentists to learn about the existence of this pathology and be able to recognize it in order to avoid its complications and spread (AU)

Perfil clínico e fatores associados ao óbito de pacientes COVID-19 nos primeiros meses da pandemia / Perfil clínico y factores asociados a la muerte de pacientes COVID-19 en los primeros meses de la pandemia / Clinical profile and factors associated with the death of COVID-19 patients in the first months of the pandemic

RESUMO Objetivo analisar as características individuais, clínicas e os fatores associados à mortalidade de pacientes com COVID-19, em hospital público do estado do Paraná, Brasil. Métodos estudo seccional, retrospectivo, documental (n= 86), com pacientes adultos internados, de março a junho de 2020. Resultados a mortalidade foi de 12,8%, o grupo de maior risco foi de idosos com comorbidades, especialmente, cardiovasculares. A chance de óbito foi 58 vezes maior em idosos, comparada aos adultos, e oito vezes maior naqueles com comorbidades, comparadas aos hígidos. A maioria dos pacientes apresentou sintomatologia respiratória, febre e mialgia. Tratamento à base de antibióticos, anticoagulantes e antivirais, associado ao suporte ventilatório. As principais complicações foram hipóxia, insuficiência renal aguda e infecção secundária. Conclusão e implicações para a prática idosos com comorbidades cardiovasculares que necessitaram de cuidados intensivos apresentaram maior chance de óbito. Os resultados de um dos centros de referência na pandemia possibilitam discutir medidas epidemiológicas adotadas, com ênfase em conceitos restritivos nos primeiros meses.

RESUMEN Objetivo analizar las características individuales, clínicas y los factores asociados a la mortalidad en pacientes con COVID-19 en un hospital público del estado de Paraná. Métodos estudio transversal, retrospectivo, documental (n = 86), con pacientes adultos hospitalizados, de marzo a junio de 2020. Resultados la mortalidad fue del 12,8%, grupo de mayor riesgo para los ancianos con comorbilidades, especialmente enfermedades cardiovasculares. La probabilidad de muerte fue 58 veces mayor en los ancianos en comparación con los adultos y ocho veces mayor en aquellos con comorbilidades en comparación con los sanos. La mayoría de los pacientes presentaban síntomas respiratorios, fiebre y mialgia. Tratamiento a base de antibióticos, anticoagulantes y antivirales, asociado al soporte ventilatorio. Las principales complicaciones fueron hipoxia, insuficiencia renal aguda e infección secundaria. Conclusión e implicaciones para la práctica los ancianos con comorbilidades cardiovasculares que requirieron cuidados intensivos tenían una mayor probabilidad de muerte. Los resultados de uno de los centros de referencia pandémica permiten discutir las medidas epidemiológicas adoptadas, con énfasis en conceptos restrictivos en los primeros meses.

ABSTRACT Objective to analyze the individual and clinical characteristics and the factors associated with mortality in patients with COVID-19, in a public hospital in the state of Paraná, Brazil. Methods a cross-sectional, retrospective, documentary study (n= 86), with adult inpatients, from March to June 2020. Results mortality was 12.8%, the highest risk group was the elderly with comorbidities, especially cardiovascular ones. The chance of death was 58 times higher in the elderly compared to adults, and eight times higher in those with comorbidities compared to the healthy ones. Most patients presented with respiratory symptoms, fever, and myalgia. Treatment was based on antibiotics, anticoagulants and antivirals, associated with ventilatory support. The main complications were hypoxia, acute renal failure, and secondary infection. Conclusion and implications for practice elderly people with cardiovascular comorbidities who required intensive care had a higher chance of death. The results from one of the reference centers in the pandemic make it possible to discuss epidemiological measures adopted, with emphasis on restrictive concepts in the first months.

Bixinoids Derived from Bixa orellana as a Potential Zika Virus Inhibitor Using Molecular Simulations. Antiviral Effect on the Zika Virus of Bixinoids

Abstract Zika fever is a viral infection of great relevance in public health, especially in tropic regions, in which there is a predominance of mosquitoes of the genus Aedes, vectors of the disease. Microcephaly in neonatal children and Guillain-Barré syndrome in adults can be caused by the action of the Zika virus (ZIKV). Non-structural proteins, such as NS2B, NS3 and NS5, are important pharmacological targets, due to their action in the life cycle. The absence of anti-Zika drugs raises new research, including prospecting for natural products. This work investigated the in silico antiviral activity of bixin and six other derived molecules against the Zika viral proteins NS2B-NS3 and NS5. The optimized structure was subjected to molecular docking to characterize the interaction between bixinoids and ZIKV non-structural proteins, where significant interactions were observed with amino acid residues in the catalytic site in each enzyme. These results suggest that bixin and ethyl bixin has the potential to interfere with the enzymatic activity of NS2B, NS3 and NS5, thus being an indication of being a promising anti-Zika agent.

Use of remdesivir in patients with COVID-19: a systematic review and meta-analysis / Uso de remdesivir em pacientes com COVID-19: revisão sistemática e meta-análise

ABSTRACT Objective: Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the use of remdesivir for the treatment of patients hospitalized with moderate to severe COVID-19. Methods: This was a systematic review and meta-analysis including phase 3 randomized clinical trials (RCTs) and observational cohort studies selected from various databases, comparing patients hospitalized with moderate to severe COVID-19 receiving remdesivir and controls. Results: A total of 207 studies were retrieved, 9 of which met the eligibility criteria and were included in the study. The meta-analysis using RCTs alone showed no statistically significant differences regarding mortality or use of mechanical ventilation/extracorporeal membrane oxygenation between remdesivir and control groups, and the quality of evidence was moderate and low, respectively. The use of remdesivir increased the recovery rate by 6% (95% CI, 3-9); p = 0.004) and the clinical improvement rate by 7% (95% CI, 1-14); p = 0.02). Additionally, no significant differences in mortality were found between remdesivir and control groups when the meta-analysis used observational cohort studies alone (risk difference = −0.01 (95% CI, −0.02 to 0.01; p = 0.32), the quality of evidence being moderate, and the risk of adverse events was 4% ([95% CI, −0.08 to 0.01]; p = 0.09). Conclusions: The use of remdesivir for the treatment of patients with moderate to severe COVID-19 had no significant impact on clinically important outcomes.

RESUMO Objetivo: Estudos na literatura sobre o uso de remdesivir no tratamento de pacientes com COVID-19 têm apresentado resultados divergentes. O objetivo deste estudo foi responder a perguntas a respeito do uso de remdesivir no tratamento de pacientes hospitalizados com COVID-19 moderada a grave. Métodos: Trata-se de uma revisão sistemática e meta-análise de ensaios clínicos controlados randomizados (ECR) de fase 3 e estudos observacionais de coorte recuperados de diversos bancos de dados, comparando pacientes hospitalizados com COVID-19 moderada a grave recebendo remdesivir a controles. Resultados: Foram recuperados 207 estudos, dos quais 9 preencheram os critérios de elegibilidade e foram incluídos no estudo. A meta-análise somente dos ECR não mostrou diferenças estatisticamente significativas entre os grupos remdesivir e controle quanto à mortalidade ou ao uso de ventilação mecânica/oxigenação por membrana extracorpórea, e a qualidade das evidências foi moderada e baixa, respectivamente. O uso de remdesivir aumentou a taxa de recuperação em 6% (IC95%: 3-9; p = 0,004) e a taxa de melhora clínica em 7% (IC95%: 1-14; p = 0,02). Além disso, não foram observadas diferenças significativas entre os grupos remdesivir e controle quanto à mortalidade quando a meta-análise concentrou-se apenas nos estudos observacionais de coorte [diferença de risco = −0,01 (IC95%: −0,02 a 0,01); p = 0,32; qualidade das evidências: moderada], e o risco de eventos adversos foi de 4% (IC95%: −0,08 a 0,01; p = 0,09). Conclusões: O uso de remdesivir no tratamento de pacientes com COVID-19 moderada a grave não teve impacto significativo em desfechos clinicamente importantes.

Comparison of tenofovir alafenamide and entecavir for hepatitis B virus-related acute-on-chronic liver failure / 中南大学学报(医学版)

OBJECTIVES@#Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure in China, with a high mortality. Early rapid reduction of HBV-DNA load can improve the survival rate of HBV-ACLF patients. At present, the commonly used drugs are nucleoside (acid) analogues, such as entecavir (ETV), tenofovir, and so on. The newly listed tenofovir alafenamide fumarate (TAF) has attracted great attention of clinicians because of its stronger antiviral effect, higher transaminase normalization rate, better bone and kidney safety, and zero drug resistance. However, there are few clinical research data on the efficacy and safety of TAF in the treatment of Chinese HBV-ACLF patients, and there is a lack of pharmacoeconomic evaluation. This study aims to compare the efficacy, safety, and cost-effectiveness between TAF and ETV in patients with HBV-ACLF.@*METHODS@#The data were collected from 196 HBV-ACLF patients (80 patients in the TAF group and 116 patients in the ETV group) who were hospitalized in Xiangya Hospital, Central South University from May 2020 to March 2021. Biochemistry and virology were detected before and after treatment (at baseline, Week 2, 4, and 12). Clinical features, disease prognosis, and cost-effectiveness were compared between the 2 groups. According to the baseline, HBV-ACLF patients were divided into 4 stages including pre-liver failure stage, early stage, medium stage, and end stage. And the liver transplantation rate and mortality was also compared. Pharmacoeconomic evaluation was taken using cost-effectiveness analysis and cost minimization analysis．.@*RESULTS@#After 4 weeks of treatment, there were no significant differences in the efficacy (liver function, viral load) between the 2 groups (all P>0.05). The TAF group showed lower creatinine [(80.35±18.77) μmol/L vs (105.59±82.32) μmol/L, P<0.05] and higher estimated glomerular filtration rate (eGFR) levels [(95.65±23.21) mL/(min·1.73 m2) vs (82.68±26.32) mL/(min·1.73 m2), P<0.05] than the ETV group. After 12 weeks of treatment, the analysis of overall the liver transplantation rate and mortality between the 2 groups showed similar conclusion. However, the TAF group had a lower the liver transplantation rate and mortality than the ETV group in patients with pre-liver failure (0vs13.89%, P<0.05). No evident distinction was found in the liver transplantation rate and mortality during the early, medium, or end stages of liver failure (13.04% vs 17.65%, 37.50% vs 37.04%, and 54.55% vs 68.42%, respectively). Ratio of cost to effectiveness in the ETV group was higher than that in the TAF group.@*CONCLUSIONS@#TAF is not more efficient than ETV group in improving liver function and reducing viral load for HBV-ACLF patients and they also show similar safety. However, TAF has a greater advantage over ETV not only in preserving renal function, but also in reducing the liver transplantation rate and mortality in patients with pre-liver failure. TAF can provide economic benefit to patients with HBV-ACLF.

In Silico Screening of Natural Products as Potential Inhibitors of SARS-CoV-2 Using Molecular Docking Simulation / 中国结合医学杂志

OBJECTIVE@#To explore potential natural products against severe acute respiratory syndrome coronavirus (SARS-CoV-2) via the study of structural and non-structural proteins of human coronaviruses.@*METHODS@#In this study, we performed an in-silico survey of 25 potential natural compounds acting against SARS-CoV-2. Molecular docking studies were carried out using compounds against 3-chymotrypsin-like protease (3CLPRO), papain-like protease (PLPRO), RNA-dependent RNA polymerase (RdRp), non-structural protein (nsp), human angiotensin converting enzyme 2 receptor (hACE2R), spike glycoprotein (S protein), abelson murine leukemia viral oncogene homolog 1 (ABL1), calcineurin-nuclear factor of activated T-cells (NFAT) and transmembrane protease serine 2.@*RESULTS@#Among the screened compounds, amentoflavone showed the best binding affinity with the 3CLPRO, RdRp, nsp13, nsp15, hACE2R. ABL1 and calcineurin-NFAT; berbamine with hACE2R and ABL1; cepharanthine with nsp10, nsp14, nsp16, S protein and ABL1; glucogallin with nsp15; and papyriflavonol A with PLPRO protein. Other good interacting compounds were juglanin, betulinic acid, betulonic acid, broussooflavan A, tomentin A, B and E, 7-methoxycryptopleurine, aloe emodin, quercetin, tanshinone I, tylophorine and furruginol, which also showed excellent binding affinity towards a number of target proteins. Most of these compounds showed better binding affinities towards the target proteins than the standard drugs used in this study.@*CONCLUSION@#Natural products or their derivatives may be one of the potential targets to fight against SARS-CoV-2.

Rational selection of virologic and immunological biomarkers and therapeutic endpoints in the clinical trials of new drugs treating chronic hepatitis B / 中华肝脏病杂志

Hepatitis B virus (HBV) infection remains to be the major cause of chronic liver diseases in China. Since the nucleos(t)ide analogues and pegylated interferon-alpha do not directly target the covalently closed circular DNA (cccDNA) in the nuclei of HBV-infected hepatocytes, those standard-of-care medications cannot efficiently cure the infected hepatocytes and rarely achieve the functional cure of chronic hepatitis B (CHB). Therefore, new antiviral drugs targeting distinct steps of HBV replication and immunotherapeutics reinvigorating antiviral immune responses are urgently needed for the functional cure of CHB. Based on the extensive discussion of the biological and clinical significance of new virologic biomarkers and distinct mechanism of drug candidates currently in clinical development, we propose that the selection of virologic and immunological biomarkers for evaluation of therapeutic efficacy as well as setting the therapeutic endpoints in the clinical trials should be based on the mode of action of investigational drugs. In addition, due to the complexity of CHB pathogenesis, selection of specific subpopulation of CHB patients for the clinical trials of drugs with a specific mode of action should also be considered.

Vasoactive intestinal peptide: a potential target for antiviral therapy / 生理学报

Viral infection is clinically common and some viral diseases, such as the ongoing global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have high morbidity and mortality. However, most viral infections are currently lacking in specific therapeutic agents and effective prophylactic vaccines, due to inadequate response, increased rate of drug resistance and severe adverse side effects. Therefore, it is urgent to find new specific therapeutic targets for antiviral defense among which "peptide-based therapeutics" is an emerging field. Peptides may be promising antiviral drugs because of their high efficacy and low toxic side effects. Vasoactive intestinal peptide (VIP) is a prospective antiviral peptide. Since its successful isolation in 1970, VIP has been reported to be involved in infections of SARS-CoV-2, human immune deficiency virus (HIV), vesicular stomatitis virus (VSV), respiratory syncytial virus (RSV), Zika virus (ZIKV) and cytomegalovirus (CMV). Additionally, given that viral attacks sometimes cause severe complications due to overaction of inflammatory and immune responses, the potent anti-inflammatory and immunoregulator properties of VIP facilitate it to be a powerful and promising candidate. This review summarizes the role and mechanisms of VIP in all reported viral infections and suggests its clinical potential as an antiviral therapeutic target.

Effects of hepatitis B virus on Th17, Treg and Th17/Treg ratio in different alanine aminetransferase stages / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effects of hepatitis B virus (HBV) on helper T lymphocytes 17 (Th17), regulatory T lymphocyte (Treg) and Th17/Treg ratio in chronic hepatitis B patients in different alanine aminetransferase (ALT) stages.@*METHODS@#In the study, 336 chronic hepatitis B patients in the first hospital of Lanzhou University were analyzed. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the HBV loads were measured by quantitative PCR, Th17, Treg and Th17/Treg ratios were detected by flow cytometry. Among them, 111 cases (ALT < 40 U/L) of ALT were normal hepatitis B, 108 cases of chronic hepatitis B with ALT above normal upper limit and < 2 times higher (40 U/L≤ALT < 80 U/L), and 117 cases of chronic hepatitis B with ALT above 2 times normal upper limit (80 U/L≤ALT). According to the viral load, they were divided into low replication group with HBV DNA < 4.0 lg copies/mL, medium replication group with 4.0 lg copies/mL≤HBV DNA < 6.0 lg copies/mL and high replication group with HBV DNA ≥ 6.0 lg copies / mL. Dunnett T3 variance analysis were used to analyze the effects of HBV on Th17, Treg and Th17/Treg ratio in the chronic hepatitis B patients in different ALT stages. The changes of virological and immunological indexes before and after treatment were observed for 24 weeks of antiviral therapy in the hepatitis B patients with ALT≥double upper limit of normal group.@*RESULTS@#In the ALT normal group, different virus load HBV had minor effects on Th17, Treg and Th17/Treg ratio. In the ALT≥2 times upper limit of normal group, with the virus load increased, Th17 (3.18%±0.79% in low replication group, 3.78%±0.92% in medium replication group and 4.57%±1.15% in high replication group), Treg cells (5.52%±1.58% in low replication group, 5.89%±1.84% in medium replication group and 6.37%±2.35% in high replication group) and their ratio Th17/Treg (0.57±0.25 in low replication group, 0.65±0.29 in medium replication group and 0.73±0.36 in high replication group) were significantly increased (P < 0.05). After entecavir treatment 24 weeks, the patient' s HBV-DNA decreased significantly, Th17 (3.89%±1.02% vs. 2.06%±0.46%), Treg (6.02%±2.03% vs. 5.06%±1.25%), Th17/Treg ratio (0.65±0.28 vs. 0.41±0.14) decreased significantly (P < 0.05).@*CONCLUSION@#Investigation on the effects of HBV on Th17 and Treg cells and their ratios in different ALT states can clarify the effects of HBV on the body from the immunological perspective and can further understand the ALT grouping for antiviral treatment theoretical significance, which is helpful for clinical treatment.

A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China / 中华肝脏病杂志

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA / 中华肝脏病杂志

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

Observation of PD-1+CXCR5+CD4+T lymphocyte and sPD-1 levels in HBeAg positive chronic hepatitis B virus carriers treated with entecavir / 中华肝脏病杂志

Objective: To dynamically observe the clinical efficacy of entecavir and the changes of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 levels in peripheral blood of HBeAg-positive chronic hepatitis B virus carriers treated with entecavir, and further explore its clinical significance. Methods: There were 31 cases of chronic hepatitis B virus carriers in the treatment group (A), 32 cases of chronic hepatitis B virus carriers in the treatment group (B), and 15 cases of chronic hepatitis B virus carriers in the non-treatment group (C).Three groups peripheral blood samples and clinical data at 0, 24 and 48 weeks were collected and compared. PD-1+CXCR5+CD4+T lymphocytes were detected by flow cytometry, and the level of sPD-1 was detected by enzyme-linked immunosorbent assay. ANOVA and Spearman correlation analysis were performed on the measurement data among the three groups. Results: At week 0, the serum levels of HBsAg, HBeAg and HBV DNA were significantly higher in groups A and C than group B. PD-1+CXCR5+CD4+T lymphocytes in peripheral blood were significantly higher in group B (4.70%±1.58%) than group A (3.25%±1.01%) and group C (2.77%±0.67%) (F=16.65, P<0.05). There was no significant difference between group A and group C (P>0.05). Peripheral blood sPD-1 in group B [(1 866.62±1 472.70) pg/ml] was significantly higher than group A [(824.86±538.66) pg/ml] and group C [(618.19±602.62) pg/ml] (F=10.95, P<0.05). There was no significant difference between group A and group C (P>0.05). At 48 weeks, the serum HBsAg did not decrease significantly in groups A and C than baseline (P>0.05), but were significantly higher than group B (P<0.05). Serum HBeAg levels were decreased significantly in groups A and B than baseline (P<0.05). <0.05), but group A was significantly higher than group B (P<0.05), and there was no significant difference between group A and group C (P>0.05). Serum HBV DNA level was significantly lower in groups A and B than group C (P<0.05), and there was no significant difference between group A and group B (P>0.05). Peripheral blood PD-1+CXCR5+CD4+T lymphocytes were significantly lower in Group A (1.56%±0.73%) and group B (1.32%±0.43%) than group C (2.64%±0.85%) (P<0.05). Peripheral blood sPD-1 were significantly lower in group A [(289.05±215.86) pg/ml] and group B [(236.01±173.92) pg/ml] than group C [(650.34±598.46) pg/ml] (P<0.05). There was no significant difference between group A and group B. Correlation analysis results: In group A at 48 weeks, the decreased level of PD-1+CXCR5+CD4+T lymphocyte ratio had no correlation with the decreased level of HBsAg and HBV DNA, but was positively correlated with the decreased level of HBeAg (r=0.376, P<0.05). The decreased level of sPD-1 had no correlation with the changes of HBsAg, but was positively correlated with the decreased levels of HBeAg and HBV DNA (r=0.598 and 0.384, P<0.05). In group B at 48 weeks, the decreased levels of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 were positively correlated with the decreased levels of HBsAg, HBeAg, and HBV DNA (P<0.05). Conclusion: Hepatitis B virus replication and expressions in HBeAg-positive chronic hepatitis B virus carriers were significantly inhibited after 48 weeks of antiviral treatment, which is related not only to entecavir treatment, but also to the immunological mechanism involved in sPD-1. Moreover, the inhibition of HBeAg expression is associated with a decrease in the number and/or activity of PD-1+CXCR5+CD4+T lymphocytes.