Web-tools for the genomic analysis of the 2022 Monkeypox virus global outbreak / Herramientas web para el análisis genómico del virus de la viruela símica durante el brote mundial de 2022

Abstract The resources and platforms available on the internet for collecting and sharing information and performing genomic sequence analysis have made it possible to follow closely the evolution the evolution of SARS-CoV-2. However, the current monkeypox outbreak in the world brings us back to the need to use these resources to appraise the extent of this outbreak. The objective of this work was an analysis of the information presented so far in the genomic database GISAID EpiPox™, using various tools available on the web. The results indicate that the monkeypox outbreak is referred as MPXV clade II B.1 lineage and sub-lineages, isolated from male patients mainly from the European and American continents. In the current scenario, the access to genomic sequences, epidemiological information, and tools available to the scientific community is of great importance for global public health in order to follow the evolution of pathogens.

Resumen Los recursos y plataformas disponibles en Internet para recopilar, compartir información y realizar análisis de secuencias genómicas han permitido seguir de cerca la evolución del SARS-CoV-2. El actual brote global de viruela del mono en el mundo, requiere de nuevo utilizar estos recursos para conocer el alcance de este brote. El objetivo de este trabajo fue un análisis de la información presentada hasta el momento en la base de datos genómica EpiPox™ de GISAID, utilizando diversas herramientas disponibles en la web. Los resultados indican que el brote de la viruela del mono o símica está referido al linaje y sub-linajes B.1 del clado II de MPXV, aislado principalmente de pacientes hombres de Europa y América. En el escenario actual, el acceso a las secuencias genómicas, la información epidemiológica, y las herramientas disponibles para la comunidad científica son de gran importancia para la salud pública mundial con el fin de seguir la evolución de los patógenos.

Cambios en las características clínicas y desenlaces de pacientes hospitalizados por COVID-19 durante dos años de pandemia: experiencia en un hospital venezolano / Changes in clinical characteristics and outcomes of patients hospitalized with COVID-19 during two years of the pandemic: experience in a venezuelan hospital

RESUMEN Objetivos. Determinar los cambios en las características clínicas y desenlaces intrahospitalarios de los pacientes hospitalizados por COVID-19 en un hospital privado de Caracas durante dos años de pandemia. Materiales y métodos. Estudio retrospectivo, observacional, de pacientes hospitalizados por COVID-19. Se investigó la correspondencia entre las olas de ingresos hospitalarios con las variantes circulantes del SARS-CoV-2 en la población general del Distrito Capital y estado Miranda. Resultados. Se incluyeron 1025 pacientes (569 hombres y 456 mujeres), con edad promedio de 62,9 DE: 16,2 años. Cuatro olas de ingresos hospitalarios fueron identificadas: primera (marzo-noviembre 2020) 150/1025 (14,6%) casos; segunda (diciembre-2020 a mayo-2021) 415/1025 (40,5%) casos; tercera (junio-diciembre 2021) 344/1025 (33,6%) casos; cuarta (enero-febrero 2022) 116/1025 (11,3%) casos. La edad promedio fue mayor en la cuarta ola (primera 64,0±15,7, segunda 61,4±15,8, tercera 62,1±16,5, y cuarta ola 68,5±16,4), mientras que la proporción de pacientes masculinos (primera 66,7%, segunda 58,8%, tercera 50,3%, y cuarta 44,8%), los pacientes con enfermedad grave-crítica (primera 65,3%, segunda 57%, tercera 51,7% y cuarta 44,8%), la estadía intrahospitalaria (primera 9,1±6,0, segunda 9,0±7,3, tercera 8,8±7,7, y cuarta 6,9±5,0 días), los ingresos a la UCI (primera 23,3%, segunda 15,7%, tercera 14,0%, y cuarta 11,2%; p=0,027) y la mortalidad (primera 21.8%, segunda 10,7%, tercera 9,1%, y cuarta 7,1%; p<0,001) disminuyeron progresivamente con el tiempo. Conclusiones. Los resultados muestran menor frecuencia de casos severos y mejoría de los desenlaces intrahospitalarios en dos años de pandemia. Es probable que los cambios en las variantes circulantes, las mejoras del manejo de la enfermedad y la vacunación hayan influido sobre estos resultados.

ABSTRACT Objectives. To determine changes in the clinical characteristics and in-hospital outcomes of patients hospitalized for COVID-19 in a private hospital in Caracas during two years of the pandemic. Materials and Methods. Retrospective, observational study of patients hospitalized for COVID-19. We evaluated the correspondence between waves of hospital admissions and circulating variants of SARS-CoV-2 in the general population of the Capital District and Miranda state. Results. A total of 1025 patients (569 men and 456 women) were included, with a mean age of 62.9 SD: 16.2 years. Four waves of hospital admissions were identified: first (March-November 2020) 150/1025 (14.6%) cases; second (December 2020 to May 2021) 415/1025 (40.5%) cases; third (June-December 2021) 344/1025 (33.6%) cases; fourth (January-February 2022) 116/1025 (11.3%) cases. The mean age was higher in the fourth wave (first: 64.0±15.7, second: 61.4±15.8, third: 62.1±16.5, and fourth wave: 68.5±16.4), while the proportion of male patients (first: 66.7%, second: 58.8%, third: 50.3%, and fourth wave: 44.8%), patients with severe-critical illness (first: 65.3%, second: 57%, third: 51.7%, and fourth wave: 44.8%), in-hospital stay (first: 9.1±6.0, second: 9.0±7.3, third: 8.8±7.7, and fourth wave: 6.9±5.0 days), ICU admissions (first: 23.3%, second: 15.7%, third: 14.0%, and fourth wave: 11.2%; p=0.027) and mortality (first: 21. 8%, second: 10.7%, third: 9.1%, and fourth wave: 7.1%; p<0.001) progressively decreased over time. Conclusions. The results show lower frequency of severe cases and improvement of in-hospital outcomes in two years of the pandemic. Changes in circulating variants, improvements in disease management and vaccination are likely to have influenced these results.

Sub-lineages of the Omicron variant of SARS-CoV-2: characteristic mutations and their relation to epidemiological behavior / Sub-linajes de la variante Ómicron del SARS-CoV-2: mutaciones características y su relación con el comportamiento epidemiológico

Abstract By the end of 2021, the Omicron variant of SARS-CoV-2, the coronavirus responsible for COVID-19, emerges, causing immediate concern, due to the explosive increase in cases in South Africa and a large number of mutations. This study describes the characteristic mutations of the Omicron variant in the Spike protein, and the behavior of the successive epidemic waves associated to the sub-lineages throughout the world. The mutations in the Spike protein described are related to the virus ability to evade the protection elicited by current vaccines, as well as with possible reduced susceptibility to host proteases for priming of the fusion process, and how this might be related to changes in tropism, a replication enhanced in nasal epithelial cells, and reduced in pulmonary tissue; traits probably associated with the apparent reduced severity of Omicron compared to other variants.

Resumen A finales de 2021 surge la variante Omicron del SARS-CoV-2, el coronavirus responsable de la COVID-19, causando preocupación inmediata, debido al aumento explosivo de casos en Suráfrica, y a su gran cantidad de mutaciones. Este estudio describe las mutaciones características de la variante Ómicron en la proteína de la Espiga (S) y el comportamiento de las sucesivas olas epidémicas asociadas a la circulación de sus sub-linajes en todo el mundo. Las mutaciones en la proteína S descritas están relacionadas con su capacidad para evadir la protección provocada por las vacunas actuales, así como su posible susceptibilidad reducida a las proteasas del hospedero para la preparación del proceso de fusión. Se infiere cómo esto podría estar relacionado con su cambio en el tropismo, con una replicación mayor en las células epiteliales nasales y menor en el tejido pulmonar, rasgos probablemente asociados a su aparente menor gravedad en comparación con otras variantes.

Detection of the Omicron variant of SARSCoV-2 by restriction analysis targeting the mutations K417N and N440K of the spike protein / Detección de la Variante Ómicron del SARS-CoV-2 por análisis de restricción de dos mutaciones de la proteína de la espiga

Abstract By the end of 2021, the Omicron variant of concern (VOC) emerges in South Africa. This variant caused immediate concern, due to the explosive increase in cases associated with it and the large number of mutations it exhibits. In this study, the restriction sites that allow detecting the mutations K417N and N440K in the Spike gene are described. This analysis allows us to propose a rapid method for the identification of cases infected with the Omicron variant. We show that the proposed methodology can contribute to provide more information on the prevalence and rapid detection of cases of this new VOC.

Resumen Para finales de 2021 surge la variante de preocupación (VOC por sus siglas en inglés) Ómicron en Sudáfrica. Esta variante causó de forma inmediata preocupación, debido al aumento explosivo de casos asociados a ella y al gran número de mutaciones que exhibe. En este estudio, se describen los sitios de restricción que permiten detectar dos de estas mutaciones en el gen de la espiga, las mutaciones K417N y N440K. Este análisis permite proponer un método rápido para la identificación de casos infectados con la variante Ómicron. Mostramos que la metodología propuesta puede contribuir a proporcionar más información sobre la prevalencia y a detectar rápidamente los casos de esta nueva VOC.

Hepatitis B virus American genotypes: Pathogenic variants ?

Hepatitis B virus (HBV) chronic infection is responsible for almost 900.000 deaths each year, due to cirrhosis or hepatocellular carcinoma (HCC). Ten HBV genotypes have been described (A-J). HBV genotype F and H circulate in America. HBV genotypes have been further classified in subgenotypes. There is a strong correlation between the genetic admixture of the American continent and the frequency of genotypes F or H: a high frequency of these genotypes is found in countries with a population with a higher ratio of Amerindian to African genetic admixture. The frequency of occult HBV infection in Amerindian communities from Latin America seems to be higher than the one found in other HBV-infected groups, but its association with American genotypes is unknown. There is growing evidence that some genotypes might be associated with a faster evolution to HCC. In particular, HBV genotype F has been implicated in a frequent and rapid progression to HCC. However, HBV genotype H has been associated to a less severe progression of disease. This study reviews the diversity and frequency of autochthonous HBV variants in the Americas and evaluates their association to severe progression of disease. Although no significant differences were found in the methylation pattern between different genotypes and subgenotypes of the American types, basal core promoter mutations might be more frequent in some subgenotypes, such as F1b and F2, than in other American subgenotypes or genotype H. F1b and probably F2 may be associated with a severe presentation of liver disease as opposed to a more benign course for subgenotype F4 and genotype H. Thus, preliminary evidence suggests that not all of the American variants are associated with a rapid progression to HCC.

Presente y futuro de la terapia contra la hepatitis C / Present and future of therapy against hepatitis C

Un 3% de la población mundial está infectado por el virus de la hepatitis C (VHC). Un 70-80% de los individuos infectados desarrollan una infección crónica. No se dispone de una vacuna contra la hepatitis C y aproximadamente 50% de los pacientes infectados no responden a la terapia estándar basada en la combinación de interferón-alfa (IFN-α) y ribavirina. Recientemente se han hecho disponibles drogas antivirales de acción directa contra el VHC, que representan una mejora significativa en el éxito terapéutico. En el 2014, la agencia reguladora de drogas y alimentos de Estados Unidos (de sus siglas en inglés FDA), aprobó el uso de ledipasvir más sofosbuvir para el tratamiento crónico de la infección, siendo el primer régimen aprobado que no requiere la administración de IFN-α ó ribavirina. Estos avances hacen esperar la erradicación de esta enfermedad, si no fuera por los altos costos asociados al tratamiento. Una alternativa emergente es la terapia enfocada a la inhibición de blancos celulares que intervienen en la infección por el VHC. Esta terapia podría aumentar tanto el número de opciones para la terapia como la barrera genética para la selección de variantes virales resistentes. El tratamiento de la hepatitis C podría llevar al uso de la terapia enfocada en blancos celulares en combinación con la terapia tradicional, esperando un posible efecto sinérgico.

Around 3% of the human population is infected with hepatitis C virus (HCV) and 70-80% of these individuals develop a chronic infection. There is no vaccine available against HCV and up to 50% of the infected patients do not respond to standard therapy, based on the combination of interferon-alpha (IFN-α) and ribavirin. Recently, direct acting antiviral drugs against HCV have been made available for treatment, leading to a significant improvement in therapeutic success. In 2014, the U.S. Food and Drug Administration approved ledipasvir plus sofosbuvir to treat the chronic infection, the first IFN- and ribavirin-free approved treatment. With such treatment, the eradication of the disease would be feasible, although drug costs are high. Host target therapy represents an emerging alternative, based on the understanding of host factors involved in the HCV infection. This therapy might show at least two theoretical benefits, increasing the number of options for therapy and raising the genetic barrier for selection of resistant variants. New treatment regimens may consist of classical therapy combined with host target-based therapy, hopefully in a synergistic manner.

Prevalence of amino acid mutations in hepatitis C virus core and NS5B regions among Venezuelan viral isolates and comparison with worldwide isolates.

BACKGROUND: Recent reports show that R70Q and L/C91M amino acid substitutions in the core from different hepatitis C virus (HCV) genotypes have been associated with variable responses to interferon (IFN) and ribavirin (RBV) therapy, as well to an increase of hepatocellular carcinoma (HCC) risk, liver steatosis and insulin resistance (IR). Mutations in NS5B have also been associated to IFN, RBV, nucleoside and non-nucleoside inhibitors drug resistance. The prevalence of these mutations was studied in HCV RNA samples from chronically HCV-infected drug-naïve patients. METHODS: After amplification of core and NS5B region by nested-PCR, 12 substitutions were analyzed in 266 Venezuelan HCV isolates subtype 1a, 1b, 2a, 2c, 2b, 2j (a subtype frequently found in Venezuela) and 3a (n = 127 and n = 228 for core and NS5B respectively), and compared to isolates from other countries (n = 355 and n = 646 for core and NS5B respectively). RESULTS: R70Q and L/C91M core substitutions were present exclusively in HCV G1b. Both substitutions were more frequent in American isolates compared to Asian ones (69% versus 26%, p < 0.001 and 75% versus 45%, p < 0.001 respectively). In Venezuelan isolates NS5B D310N substitution was detected mainly in G3a (100%) and G1a (13%), this later with a significantly higher prevalence than in Brazilian isolates (p = 0.03). The NS5B mutations related to IFN/RBV treatment D244N was mainly found in G3a, and Q309R was present in all genotypes, except G2. Resistance to new NS5B inhibitors (C316N) was only detected in 18% of G1b, with a significantly lower prevalence than in Asian isolates, where this polymorphism was surprisingly frequent (p < 0.001). CONCLUSIONS: Genotypical, geographical and regional differences were found in the prevalence of substitutions in HCV core and NS5B proteins. The substitutions found in the Venezuelan G2j type were similar to that found in G2a and G2c isolates. Our results suggest a high prevalence of the R70Q and L/C91M mutations of core protein for G1b and D310N substitution of NS5B protein for the G3a. C316N polymorphism related with resistance to new NS5B inhibitors was only found in G1b. Some of these mutations could be associated with a worse prognosis of the disease in HCV infected patients.