Population-Level Effectiveness of an Inactivated Whole-Virion COVID-19 Vaccine: A Test Negative Case-Control Study in the Dominican Republic.

Background: A continuing nationwide vaccination campaign began in the Dominican Republic on February 16, 2021 to prevent severe consequences of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Estimates of vaccine effectiveness under real-world conditions are needed to support policy decision making and inform further vaccine selection. Methods: We conducted a test-negative case-control study to assess the real-world effectiveness of nationwide coronavirus disease 2019 (COVID-19) vaccination program using an inactivated vaccine (CoronaVac) on preventing symptomatic SARS-CoV-2 infections and hospitalizations from August to November 2021 in the Dominican Republic. Participants were recruited from 10 hospitals in 5 provinces to estimate the effectiveness of full immunization (≥14 days after receipt of the second dose) and partial immunization (otherwise with at least 1 dose ≥14 days after receipt of the first dose). Results: Of 1078 adult participants seeking medical care for COVID-19-related symptoms, 395 (36.6%) had positive polymerase chain reaction (PCR) tests for SARS-CoV-2; 142 (13.2%) were hospitalized during 15 days of follow up, including 91 (23%) among 395 PCR-positive and 51 (7.5%) among 683 PCR-negative participants. Full vaccination was associated with 31% lower odds of symptomatic infection (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.52-0.93) and partial vaccination was associated with 49% lower odds (OR, 0.51; CI, 0.30-0.86). Among 395 PCR-positive participants, full vaccination reduced the odds of COVID-19-related hospitalization by 85% (OR, 0.15; 95% CI, 0.08-0.25) and partial vaccination reduced it by 75% (OR, 0.25; 95% CI, 0.08-0.80); full vaccination was associated with reduced use of assisted ventilation by 73% (OR, 0.27; 95% CI, 0.15-0.49). Conclusions: Given the ancestral and delta viral variants circulating during this study period, our results suggest that the inactivated COVID-19 vaccine offered moderate protection against symptomatic SARS-CoV-2 infections and high protection against COVID-19-related hospitalizations and assisted ventilation. This is reassuring given that, as of August 2022, an estimated 2.6 billion inactivated CoronaVac vaccine doses had been administered worldwide. This vaccine will become a basis for developing multivalent vaccine against the currently circulating omicron variant.

Terapia de REGEN COV como base de terapia inmunomoduladora mixta en pacientes hospitalizados por neumonía por SARS-CoV-2: Serie de casos / REGEN COV Therapy as the Basis of Mixed Immunomodulatory Therapy in Patients Hospitalized for SARS- CoV-2 Pneumonia: Case Series

Los países en desarrollo con sistema de salud de baja inversión encuentran un reto en priorizar el tratamiento de COVID-19 según su eficacia y sus costos. Materiales y métodos: se explora la utilidad hospitalaria de una intervención segura con eficacia ambulatoria comprobada. Se describe la administración de un tratamiento inmunomodulador combinado a base de imdevimab y casirivimab (REGEN COV). Resultados: los resultados individualizados apuntan a resultados prometedores en pacientes de alto riesgo a progresión y mortalidad. Conclusión: se ha demostrado que REGEN COV es eficiente para tratar dicha enfermedad. Sin embargo, se necesitan ensayos clínicos aleatorizados para comprobar su eficacia en combinación. (AU)

Developing countries with low-investment health systems find it challenging to prioritize COVID-19 treatment according to its efficacy and affordability. Materials and methods: therefore, the in-hospital utility of a safe intervention with outpatient efficacy is explored. We describe the administration of immunomodulatory combination therapy based on imdevimab and casirivimab (REGEN COV). Results: individualized results point to promising outcomes in patients at high risk of progression and mortality. Conclusion: REGEN COV has been shown to be efficient in treating said disease. However, randomized clinical trials are needed to verify their efficacy in combination. (AU)

Draft Genome Sequence of an Isolate of Genotype VII Newcastle Disease Virus Isolated from an Outbreak in Fighting Cock in Peru.

This study presents a draft genome sequence of a Newcastle disease virus (NDV) strain (VFAR-136) isolated from a fighting cock (Gallus gallus) in the south of Peru. Strain VFAR-136 is a new report of NDV genotype VII circulating in Peru.

Intranasal vaccination of hamsters with a Newcastle disease virus vector expressing the S1 subunit protects animals against SARS-CoV-2 disease.

The coronavirus disease-19 (COVID-19) pandemic has already claimed millions of lives and remains one of the major catastrophes in the recorded history. While mitigation and control strategies provide short term solutions, vaccines play critical roles in long term control of the disease. Recent emergence of potentially vaccine-resistant and novel variants necessitated testing and deployment of novel technologies that are safe, effective, stable, easy to administer, and inexpensive to produce. Here we developed three recombinant Newcastle disease virus (rNDV) vectored vaccines and assessed their immunogenicity, safety, and protective efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice and hamsters. Intranasal administration of rNDV-based vaccine candidates elicited high levels of neutralizing antibodies. Importantly, the nasally administrated vaccine prevented lung damage, and significantly reduced viral load in the respiratory tract of vaccinated animal which was compounded by profound humoral immune responses. Taken together, the presented NDV-based vaccine candidates fully protected animals against SARS-CoV-2 challenge and warrants evaluation in a Phase I human clinical trial as a promising tool in the fight against COVID-19.

A Recombinant Turkey Herpesvirus Expressing the F Protein of Newcastle Disease Virus Genotype XII Generated by NHEJ-CRISPR/Cas9 and Cre-LoxP Systems Confers Protection against Genotype XII Challenge in Chickens.

In this study, we developed a new recombinant virus rHVT-F using a Turkey herpesvirus (HVT) vector, expressing the fusion (F) protein of the genotype XII Newcastle disease virus (NDV) circulating in Peru. We evaluated the viral shedding and efficacy against the NDV genotype XII challenge in specific pathogen-free (SPF) chickens. The F protein expression cassette was inserted in the unique long (UL) UL45-UL46 intergenic locus of the HVT genome by utilizing a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 gene-editing technology via a non-homologous end joining (NHEJ) repair pathway. The rHVT-F virus, which expressed the F protein stably in vitro and in vivo, showed similar growth kinetics to the wild-type HVT (wtHVT) virus. The F protein expression of the rHVT-F virus was detected by an indirect immunofluorescence assay (IFA), Western blotting, and a flow cytometry assay. The presence of an NDV-specific IgY antibody was detected in serum samples by an enzyme-linked immunosorbent assay (ELISA) in SPF chickens vaccinated with the rHVT-F virus. In the challenge experiment, the rHVT-F vaccine fully protects a high, and significantly reduced, virus shedding in oral at 5 days post-challenge (dpc). In conclusion, this new rHVT-F vaccine candidate is capable of fully protecting SPF chickens against the genotype XII challenge.

Enfermedad de hígado graso no alcohólico y potenciales efectos de los β-glucanos en su tratamiento: Una revisión de literatura

RESUMEN La enfermedad de hígado graso no alcohólico es considerada hoy en día un problema de salud pública. Se caracteriza por la acumulación de ácidos grasos y de triglicéridos en el citoplasma de los hepatocitos, con aumento del peso total del hígado, que va desde una esteatosis hepática no alcohólica (ausencia de inflamación) hasta una esteatohepatitis no alcohólica (presencia de inflamación), fibrosis e incluso hepatocarcinoma. Actualmente, no cuenta con un tratamiento aprobado por agencias regulatorias de la enfermedad y se ha convertido en la enfermedad hepática con mayor prevalencia mundial. Los β-glucanos son homopolisacáridos de glucosa a los que se les atribuyen propiedades para la reducción de grasas debido a que son considerados fibra dietética. En esta revisión de literatura, se resaltó la importancia y los efectos de los β-glucanos en la dieta para su tratamiento como prevención de la enfermedad del hígado graso no alcohólico.

ABSTRACT Non-alcoholic fatty liver disease is considered a public health problem, characterized by the accumulation of fatty acids and triglycerides in the cytoplasm of hepatocytes, resulting in an increase in the total weight of the liver, ranging from a non-alcoholic hepatic steatosis (absence of inflammation) to non-alcoholic steatohepatitis (presence of inflammation), fibrosis and even hepatocarcinoma. Currently, there are no treatments approved by regulatory agencies for the disease, which has led to a high prevalence of liver disease worldwide. The β-glucans are homopolysaccharides of glucose to which fat-reducing properties are attributed since they are considered dietary fiber. The importance and effects of β-glucans in the diet for the prevention of nonalcoholic fatty liver disease are highlighted in this literature review.

Adaptive value of foot-and-mouth disease virus capsid substitutions with opposite effects on particle acid stability.

Foot-and-mouth disease virus (FMDV) is a picornavirus that exhibits an extremely acid sensitive capsid. This acid lability is directly related to its mechanism of uncoating triggered by acidification inside cellular endosomes. Using a collection of FMDV mutants we have systematically analyzed the relationship between acid stability and the requirement for acidic endosomes using ammonium chloride (NH4Cl), an inhibitor of endosome acidification. A FMDV mutant carrying two substitutions with opposite effects on acid-stability (VP3 A116V that reduces acid stability, and VP1 N17D that increases acid stability) displayed a rapid shift towards acid lability that resulted in increased resistance to NH4Cl as well as to concanamicyn A, a different lysosomotropic agent. This resistance could be explained by a higher ability of the mutant populations to produce NH4Cl-resistant variants, as supported by their tendency to accumulate mutations related to NH4Cl-resistance that was higher than that of the WT populations. Competition experiments also indicated that the combination of both amino acid substitutions promoted an increase of viral fitness that likely contributed to NH4Cl resistance. This study provides novel evidences supporting that the combination of mutations in a viral capsid can result in compensatory effects that lead to fitness gain, and facilitate space to an inhibitor of acid-dependent uncoating. Thus, although drug-resistant variants usually exhibit a reduction in viral fitness, our results indicate that compensatory mutations that restore this reduction in fitness can promote emergence of resistance mutants.

Descripción del riesgo cardiovascular en pacientes diabéticos tipo 1 en República Dominicana / Type 1 diabetes cardiovascular risk description in Dominican Republic

Introducción: la diabetes tipo 1 es una enfermedad crónica de alto impacto económico con gran capacidad de ser controlada, la misma no tiene ninguna descripción local previa. Su principal causa de mortalidad es los eventos cardiovasculares y el manejo adecuado la disminuye considerablemente. Objetivo: determinar el riesgo cardiovascular en pacientes adultos con diabetes tipo 1 en la ciudad de Santiago de los Caballeros, República Dominicana. Método: se realizó un estudio descriptivo transversal multicéntrico con 39 pacientes en el período de junio a noviembre de 2019. La calculadora "Steno T1 Risk Engine" se utilizó para estimar el riesgo cardiovascular. Resultados: se obtuvo una relación significativa entre la albuminuria (p = 0.0127), presión arterial sistólica (p = 0.0002), tiempo de diagnóstico (p = 0.0037) y nivel de riesgo cardiovascular. La hemoglobina glucosilada (p = 0,7884) y la actividad física (p = 0.706) no mostraron una relación significativa con el riesgo cardiovascular. Conclusión: el nivel de riesgo cardiovascular promedio es bajo, con probabilidades <10 % de un evento cardiovascular agudo dentro de los 10 años. Esta herramienta permite incluir una evaluación cardiovascular rutinaria con datos que perfilen el tratamiento orientado a disminuir complicaciones vasculares, mortalidad y aumentar adherencia al tratamiento.

Introduction: Type 1 diabetes is a chronic condition with a high economic impact but potentially controllable. There is no previous local description of this condition. Its main fatality cause is due to cardiovascular events and its proper management can diminish it. Objective: This study aimed to determine the cardiovascular risk in adult patients with type 1 diabetes mellitus in the city of Santiago de los Caballeros, Dominican Republic. Method: A descriptive multicenter cross-sectional study was done on 39 patients in the period of June-November 2019. "Steno T1 Risk Engine" calculator estimated the cardiovascular risk. Results: A significant relationship was obtained between albuminuria (p = 0.0127), systolic blood pressure (p = 0.0002), diagnosis time (p = 0.0037) and cardiovascular risk level. Glycated hemoglobin (p = 0.7884) and physical activity (p = 0.7063) did not show a significant relationship with cardiovascular risk. Conclusion: Average cardiovascular risk level is low with <10% probabilities of an acute cardiovascular event within 10 years. This tool could lead to quick cardiovascular risk evaluations to guide the treatment lowering vascular complications, mortality and increasing treatment adherence.

Genotype-matched Newcastle disease virus vaccine confers improved protection against genotype XII challenge: The importance of cytoplasmic tails in viral replication and vaccine design.

Although typical Newcastle disease virus (NDV) vaccines can prevent mortality, they are not effective in preventing viral shedding. To overcome this, genotype-matched vaccines have been proposed. To date, this approach has never been tested against genotype XII strains. In this study, we generated and assessed the protection against genotype XII challenge of two chimeric NDV vaccine strains (rLS1-XII-1 and rLS1-XII-2). The rLS1-XII-1 virus has the complete fusion protein (F) and the hemagglutinin-neuraminidase (HN) open reading frames replaced with those from genotype XII strain NDV/peacock/Peru/2011 (PP2011) in a recombinant LaSota (rLS1) backbone. In rLS1-XII-2 virus, cytoplasmic tails of F and HN proteins were restored to those of rLS1. In vitro evaluation showed that rLS1-XII-2 and the parental rLS1 strains replicate at higher efficiencies than rLS1-XII-1. In the first vaccine/challenge experiment, SPF chickens vaccinated with rLS1-XII-1 virus showed only 71.3% protection, whereas, rLS1 and rLS1-XII-2 vaccinated chickens were fully protected. In a second experiment, both rLS1-XII-2 and the commercial vaccine strain LaSota induced 100% protection. However, rLS1-XII-2 virus significantly reduced viral shedding, both in the number of shedding birds and in quantity of shed virus. In conclusion, we have developed a vaccine candidate capable of fully protecting chickens against genotype XII challenges. Furthermore, we have shown the importance of cytoplasmic tails in virus replication and vaccine competence.

Development of a novel Newcastle disease virus (NDV) neutralization test based on recombinant NDV expressing enhanced green fluorescent protein.

BACKGROUND: Newcastle disease is one of the most important infectious diseases of poultry, caused by Newcastle disease virus (NDV). This virus is distributed worldwide and it can cause severe economic losses in the poultry industry due to recurring outbreaks in vaccinated and unvaccinated flocks. Protection against NDV in chickens has been associated with development of humoral response. Although hemagglutination inhibition (HI) assay and ELISA do not corroborate the presence of neutralizing antibodies (nAbs); they are used to measure protection and immune response against NDV. METHODS: In this study, we established a system to recover a recombinant NDV (rLS1) from a cloned cDNA, which is able to accept exogenous genes in desired positions. An enhanced green fluorescent protein (eGFP) gene was engineered in the first position of the NDV genome and we generated a recombinant NDV carrying eGFP. This NDV- eGFP reporter virus was used to develop an eGFP-based neutralization test (eGFP-NT), in which nAbs titers were expressed as the reciprocal of the highest dilution that expressed the eGFP. RESULTS: The eGFP-NT gave conclusive results in 24 h without using any additional staining procedure. A total of 57 serum samples were assayed by conventional neutralization (NT) and eGFP-NT. Additionally, HI and a commercial ELISA kit were evaluated with the same set of samples. Although HI (R 2 = 0.816) and ELISA (R 2 = 0.791) showed substantial correlation with conventional NT, eGFP-NT showed higher correlation (R 2 = 0.994), indicating that eGFP-NT is more accurate method to quantify nAbs. CONCLUSIONS: Overall, the neutralization test developed here is a simple, rapid and reliable method for quantitation of NDV specific nAbs. It is suitable for vaccine studies and diagnostics.

Complete Genome Sequence of Fowl Aviadenovirus Serotype 8b Isolated in South America.

We present here the complete genome sequence of fowl aviadenovirus E (FAdV-E) serotype 8b strain FV211-16, isolated from chickens with inclusion body hepatitis in Peru. Genome comparisons with other FAdV-E strains revealed identities of 84.9 to 97.1% and the presence of 9 and 2 unique amino acid mutations in hexon and fiber proteins, respectively.

Molecular epidemiology of coxsackievirus B3 infection in Spain, 2004-2014.

Epidemiological and clinical characteristics of coxsackievirus B3 infections in Spain were investigated. This enterovirus (EV) type was detected mainly in young children (<6 months) and was associated with neurological (78 %) and respiratory diseases (10 %) but also with myo/pericarditis (10 %). Two myocarditis cases were fatal. Phylogenetic analysis of the VP1 region showed that genotype III circulated in the country between 2004 and 2008 and was replaced by genotype V in 2010. Furthermore, phylogenetic analysis of the 3D region indicated that recombination events have occurred and contributed to the genetic evolution of this EV type.

Influencia de una intervención educativa en el nivel de ansiedad de un paciente en hemodiálisis / Influence of patient education on the anxiety level of a patient on hemodialysis

Objetivo: determinar la influencia de la intervención de enfermer¡a en la disminución de ansiedad en pacientes en tratamiento con hemodiálisis en el Hospital Nacional Dos de Mayo en el año 2011. Material y métodos: estudio cuasiexperimental, con una muestra conformada por 73 pacientes que cumplieron con los criterios de selección, a los que se le aplico el Test de Zung antes y después del desarrollo de la intervención educativa. Resultados: los niveles de ansiedad de los pacientes antes de la intervención educativa y la terapia de relajación fueron: 36 (49,3%) presen taron ansiedad leve; 36 (49,3%) presentaron ansiedad moderada; 1 (1,4%) presentó ansiedad severa. Despu‚s de la intervenci¢n de enfermer¡a fueron: 34 (46,6%) no presentaron ansiedad; 38 (52,1%) presentaron ansiedad leve, y 1 (1,4%) presentó ansiedad moderada. Conclusiones: los pacientes hemodializados después de la intervención educativa mostraron una disminución considerable en el nivel de ansiedad moderado.

Objective: Determine the influence of nursing intervention in reducing anxiety in patients undergoing hemodialysis treatment at the Hospital Nacional Dos de Mayo in 2011. Material and methods: Quasi-experimental study with a sample consisting of 73 patients who met the selection criteria, to which I apply the Zung test before and after the development of the educational intervention. Results: Anxiety levels of patients before the educational intervention and relaxation therapy were: 36 (49.3%) had mild anxiety, 36 (49.3%) had moderate anxiety, 1 (1.4%) had anxiety severe. After nursing intervention were: 34 (46.6%) had no anxiety, 38 (52.1%) had mild anxiety and 1 (1.4%) had moderate anxiety. Conclusions: Hemodialysis patients after the educational intervention showed a significant decrease in the level of moderate anxiety.