Mecanismos bioquímicos en el pronóstico grave de pacientes con diabetes mellitus infectados por el virus SARS-CoV-2: revisión de la literatura / Biochemical mechanisms in the severe prognosis of patients with diabetes mellitus infected by SARS-CoV-2 virus: literature review

Resumen La diabetes mellitus (DM) es una enfermedad metabólica caracterizada principalmente por signos y síntomas derivados del aumento de glucosa sérica o hiperglucemia. La pandemia por la enfermedad del coronavirus 2019 (COVID- 19) afectó a todo el mundo con informes de pronóstico grave en pacientes diabéticos infectados por el virus del síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV-2) y elevada admisión hospitalaria en la unidad de cuidados intensivos (UCI) en comparación con pacientes no diabéticos. El objetivo del trabajo de revisión bibliográfica fue evaluar y describir algunos de los mecanismos bioquímicos que conducen al pronóstico grave en pacientes con DM infectados por el virus SARS-CoV-2 mediante la búsqueda sistemática de información en diferentes bases de datos. Los resultados mostraron que la elevada admisión a UCI con un pronóstico grave de pacientes diabéticos infectados por el virus fue por presentar inflamación excesiva que ocasiona síndrome de distrés respiratorio agudo, tormenta de citoquinas, neumonía severa, inmunidad deteriorada e hiperglucemia. El virus ingresa a la célula principalmente por la vía endocítica y no endosómica; los receptores celulares centrales implícitos en los mecanismos son receptores de insulina (RI), transportador de glucosa tipo 2 (GLUT-2), dipeptidil-peptidasa-4 (DPP4), transportador de glucosa tipo 4 (GLUT-4), enzima convertidora de angiotensina 2 (ECA2) y el correceptor proteasa transmembrana de serina 2 (TMPRSS2) esencial para la propagación viral. La mayor susceptibilidad a desarrollar COVID- 19 en pacientes diabéticos se debe a la sobreexpresión de ECA2 y las complicaciones graves se incrementan a niveles micro y macrovascular como nefropatías, neuropatías y enfermedades cardiovasculares.

Abstract Diabetes mellitus (DM) is a metabolic disease characterised mainly by signs and symptoms derived from increased serum glucose or hyperglycemia. The coronavirus disease 2019 (COVID-19) pandemic affected the entire world continenwith reports of severe prognosis in diabetic patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and high hospital admissions in the intensive care unit (ICU) compared to non-diabetic patients. The objective of the bibliographic review was to evaluate and describe some of the biochemical mechanisms that lead to severe prognosis in patients with DM infected by the SARSCoV- 2 virus through a systematic search for information in different databases. The results showed that the high ICU admission with a severe prognosis of diabetic patients infected by the virus was due to excessive inflammation that causes acute respiratory distress syndrome, cytokine storm, severe pneumonia, impaired immunity, and hyperglycemia. The virus enters the cell mainly through the endocytic and non-endosomal pathway; the central cellular receptors involved in the mechanisms are insulin receptors (IR), glucose transporter type 2 (GLUT-2), dipeptidyl peptidase-4 (DPP4), glucose transporter type 4 (GLUT-4), glucose converting enzyme angiotensin 2 (ACE2), and the serine transmembrane protease co-receptor 2 (TMPRSS2) essential for viral propagation. The increased susceptibility to developing COVID-19 in diabetic patients is due to the overexpression of ACE2, and serious complications are increased at the microvascular and macrovascular levels, such as nephropathies, neuropathies, and cardiovascular diseases.

Resumo O diabetes mellitus (DM) é uma doença metabólica caracterizada principalmente por sinais e sintomas decorrentes do aumento de glicose sérica ou hiperglicemia. A pandemia pela doença do coronavírus 2019 (COVID-19) afetou o mundo inteiro com relatos de prognóstico grave em pacientes diabéticos infectados pelo vírus da síndrome respiratória aguda grave por coronavírus 2 (SARS-CoV-2) e altas internações hospitalares na unidade de terapia intensiva (UTI) em comparação com pacientes não diabéticos. O objetivo do trabalho de revisão bibliográfica foi avaliar e descrever alguns dos mecanismos bioquímicos que levam ao prognóstico grave em pacientes com DM infectados pelo vírus SARS-CoV-2 por meio da busca sistemática de informações em diferentes bancos de dados. Os resultados mostraram que a alta admissão na UTI com prognóstico grave de pacientes diabéticos infectados pelo vírus foi devido à inflamação excessiva que apresentavam e que causa síndrome de desconforto respiratório agudo, tempestade de citocinas, pneumonia grave, imunidade prejudicada e hiperglicemia. O vírus entra na célula principalmente pela via endocítica e não endossômica; os receptores celulares centrais envolvidos nos mecanismos são os receptores de insulina (IR), transportador de glicose tipo 2 (GLUT-2), dipeptidil peptidase-4 (DPP4), transportador de glicose tipo 4 (GLUT-4), enzima conversora de angiotensina 2 (ACE2), e o co-receptor protease transmembrana de serina 2 (TMPRSS2) essencial para a propagação viral. A maior suscetibilidade ao desenvolvimento de COVID-19 em pacientes diabéticos deve-se à superexpressão de ECA2, e complicações graves aumentam nos níveis micro e macrovascular, como nefropatias, neuropatias e doenças cardiovasculares.

A emergência da dengue como desafio virológico: de doença-fantasma à endemia "de estimação", 1986-1987 / The emergence of dengue as a virological challenge: from phantom disease to "pet" endemic, 1986-1987

Resumo O artigo analisa como a dengue se apresentou como desafio virológico na década de 1980. O objetivo é entender o papel dos estudos virológicos na compreensão da doença e a construção de uma expertise em arboviroses. Embora surtos da doença já tivessem sido relatados ao longo do século XX, a dengue era pouco conhecida nas Américas até a epidemia de dengue hemorrágica em Cuba, em 1981. Quando em 1986 a doença atingiu a cidade de Nova Iguaçu (RJ), a equipe de virologistas liderada por Hermann Schatzmayr tomaria a doença como objeto, mobilizando esforços a partir da criação do Laboratório de Flavivírus do Instituto Oswaldo Cruz.

Abstract This article analyzes how dengue presented a virological challenge during the 1980s in order to explore the role of virological studies in understanding this disease and constructing expertise in arboviral diseases. Although outbreaks were reported throughout the twentieth century, dengue was barely known in the Americas until the epidemic of dengue fever in Cuba in 1981. When the disease reached the Brazilian city of Nova Iguaçu (RJ) in 1986, it became the focus of attention for a team of virologists led by Hermann Schatzmayr, who mobilized efforts after the creation of the Flavivirus Laboratory at the Oswaldo Cruz Institute.

Retos actuales a la enseñanza de la virología para enfrentar enfermedades emergentes / Current challenges to the teaching of virology to face emerging diseases

En los últimos años los microorganismos han generado múltiples evoluciones, provocando enfermedades y problemas agudos de salud pública. Para poder controlar las virosis es necesario conocer su biología y epidemiología, establecer tratamiento y profilaxis adecuada para su control. Para ello, es indispensable comenzar con la formación de los profesionales de la salud, en particular, los estudiantes de medicina, es necesario potenciar el desarrollo de sus habilidades y competencias, no solo dominio del conocimiento científico, si no también pueda promoverlo, transferirlo y aplicarlo con impacto en la salud colectiva y que vaya a la par de los avances tecno-científicos. Es por ello, que surge la inquietud del fórum, discusión acerca del análisis de la enseñanza de la virología para enfrentar enfermedades emergentes en función de perfil del egresado. Se realizó encuesta a los estudiantes de los últimos diez años de la carrera de medicina de UNIANDES, sobre la biología, epidemiologia, respuesta inmunológica y diagnóstico, para mencionadas áreas de conocimiento se obtuvo, tanto en la evaluación objetiva estructurada y evaluación práctica, un nivel altamente satisfactorio. En la pirámide de Miller, se alcanzó nivel tres con conocimiento y desarrollo de habilidades, destrezas y actitudes del egresado satisfactorias. Sin embargo, los profesores de Virología están de acuerdo con innovar en la docencia integrando los contenidos transversalmente a las áreas de conocimiento: enfermedades infecciosas, clínicas, patologías, epidemiología y salud pública, lo que permitirá un aprendizaje integral para realizar abordaje adecuado de caso positivos de las virosis, además de tener capacidades para establecer vigilancia epidemiológica(AU)

In recent years, microorganisms have generated multiple evolutions, causing diseases and acute public health problems. In order to control virosis, it is necessary to know their biology and epidemiology, establish adequate treatment and prophylaxis for their control. For this, it is essential to start with the training of health professionals, in particular, medical students, it is necessary to promote the development of their skills and competencies, not only mastery of scientific knowledge, but also be able to promote it, transfer it and apply it with an impact on collective health and that goes hand in hand with techno-scientific advances. That is why the concern of the forum arises, a discussion about the analysis of the teaching of virology to face emerging diseases based on the profile of the graduate. A survey was conducted to the students of the last ten years of the UNIANDES medical career, on biology, epidemiology, immunological response and diagnosis, for mentioned areas of knowledge it was obtained, both in the objective structured evaluation and practical evaluation, a level highly satisfactory. In the Miller pyramid, level three was reached with satisfactory knowledge and development of abilities, skills and attitudes of the graduate. However, Virology professors agree with innovating in teaching by integrating the content transversally to the areas of knowledge: infectious diseases, clinics, pathologies, epidemiology and public health, which will allow comprehensive learning to carry out an adequate approach to positive cases of virosis, in addition to having the capacity to establish epidemiological surveillance(AU)

COVID-19: Virology, Pathogenesis and Potential Therapeutics

Nowadays, the coronavirus epidemic represents a major threat to the human being, represented by great numbers of deaths and wide world life disrupt. COVID-19 virus, is not only representing a threat to the life of human being, but also to the economic activities that nearly stopped in many countries due to the partial to complete closure of life activities in order to control the wide spread of virus infections. In these extraordinary and unprecedented critical times of human being life, it is essential to review and discus the virus epidemic in trial to suggest an idea that might be beneficial to researchers to find out an exit from this dark tunnel and to prevent as possible epidemic recurrence. Many attempts of management protocols and trials all over the world, nearly failed until now to control the wide spread and the high incidence of morbidity and mortality of this viral infection. In this review, we highlight the virology and pathogenesis of epidemic and possible used therapeutics in a simplified and concise form to be easily understood and available for healthcare members and even general population. This might help in control and eradication of the current epidemic

COVID-19: profil virologique et clinique des patients diagnostiqués dans deux laboratoires à Ouagadougou, Burkina Faso / COVID-19: Virological and clinical profile of patients diagnosed in two laboratories in Ouagadougou, Burkina Faso

Contexte/objectif : La maladie à coronavirus (COVID-19) est une maladie émergente, dont l'agentpathogène est le virus du syndrome respiratoire aigu sévère dû au coronavirus 2 (SRAS-CoV-2). L'objectif de cette étudeétait de décrire le profil virologique et clinique des patients diagnostiqués dans deux laboratoires. Matériels et méthodes : Il s'est agi d'uneétude descriptive avec collecte rétrospective de données des patients atteints de COVID-19, qui a couvert la période du 04 avril au 31 décembre 2020. Le test de khi deux et le test exact de Fisher sont les tests statistiques utilisées. Résultats : Au total, 28 872 échantillons ont été testés dans les deux laboratoires. L'étude arévélé 1965 cas positifs soit 6, 80% (63 % hommes et 37,05 % femmes). La tranche d'âge de 20 à 50 ans représentait 68,68 %. La province de la capitale a enregistré autant le plus grand nombre d'échantillons (26277 soit91,00%) que le plus grand nombre des cas positifs (91,15%). Les manifestations cliniques étaient dominées par la toux 68,42%, la fatigue générale (43,86%), les céphalées (43,86%), l'écoulement nasal (40,93%), la fi èvre (39,18%). Les comorbidités les plus fréquentes étaient l'hypertension artérielle (HTA) et le diabète. Conclusion: Cette étude a montré unepopulation jeune testée. La capitale (Ouagadougou) a enregistré le plus grand nombre de demandeurs de tests et de cas positifs. La toux était la principale manifestation clinique. Les patients avec comorbidités dont l'HTA et le diabète ont été les plus nombreux a effectué le test

Background/Purpose. Coronavirus disease (COVID-19) is an emerging disease, whose pathogen is the severe acute respiratory syndrome virus due to coronavirus 2 (SARS-CoV-2). The objective of this study was to describe the virological and clinical profile of patients diagnosed in two laboratories. Methods. This was a descriptive study with retrospective data collection of patients with COVID-19, which covered the period from 04 April to 31 December 2020. Chisquare test and Fisher's exact test were used as statistical tests. Results. A total of 28,872 samples were tested in the two laboratories. The study revealed 1965 positive cases or 6, 80% (63% male and 37.05% female). The age group 20-50 years represented 68.68%. The capital province recorded both the largest number of samples (26277 or 91.00%) and the largest number of positive cases (91.15%). Clinical manifestations were dominated by cough 68.42%, general fatigue (43.86%), headache (43.86%), nasal discharge (40.93%), fever (39.18%). The most frequent comorbidities were arterial hypertension (AH) and diabetes. Conclusion. This study showed a young population tested. The capital (Ouagadougou) recorded the highest number of testers and positive cases. Cough was the main clinical manifestation. Patients with comorbidities including hypertension and diabetes were the most numerous to be tested

O coelho é a saúva: a proposta brasileira e o uso do vírus do mixoma (MYXV) contra a praga de coelhos na Austrália, 1896-1952 / Rabbits and leaf-cutting ants: the Brazilian plan to use the myxoma virus (MYXV) against rabbit plagues in Australia, 1896-1952

Resumo O artigo analisa a singularidade dos processos históricos, científicos e políticos que vão da descoberta da doença que passou a ser conhecida como mixomatose infecciosa, causada pelo vírus do mixoma (MYXV), à sua aplicação no controle de uma praga de coelhos na Austrália. A narrativa segue especialmente as pesquisas de Henrique de Beaurepaire Aragão, pesquisador do Instituto Oswaldo Cruz, e posteriormente os esforços da cientista Jean Macnamara para promover pesquisas e implementar o MYXV na Austrália. Foram consultadas notas de pesquisa de cientistas, documentos oficiais que registraram o desenvolvimento dos experimentos, bem como periódicos. Nesse processo, foi considerado o desenvolvimento histórico do campo de estudos da virologia e controle biológico.

Abstract This article analyzes the singularity of historical, scientific, and political processes from the discovery of the disease caused by the myxoma virus (MYXV) that came to be known as infectious myxomatosis to the application of this virus against a plague of rabbits in Australia. This narrative focuses on research by Henrique de Beaurepaire Aragão, a researcher at the Oswaldo Cruz Institute, and later efforts by the scientist Jean Macnamara to promote studies and implement MYXV in Australia. The scientists' research notes were consulted, along with official documents recording the experiments and periodicals. In this process, the historical development of virology and biological controls as a field of study was also considered.

Detección de SARS-CoV-2 en contactos estrechos asintomáticos de casos confirmados por diagnóstico molecular, provincia de Buenos Aires, Argentina / Detection of SARS-CoV-2 in asymptomatic close contacts of cases confirmed by molecular diagnosis, Buenos Aires province, Argentina

Resumen La detección de SARS-CoV-2 y su implicancia en el diagnóstico de COVID-19 han sido muy debatidas en la pandemia. El objetivo de este estudio fue evaluar el costo/beneficio de la detección de SARS-CoV-2 en contactos estrechos asintomáticos (CE) mediante el uso de distintas pruebas de diagnóstico molecular. Se estudiaron 51 CE de personas con diagnóstico de SARS-CoV-2 confirmado por RTqPCR, clasificadas por el umbral de ciclos (Ct) (<20, entre 20 y 30 y >30) en hospitales públicos de la provincia de Buenos Aires. Del total de contactos estudiados el 15,7% resultó confirmado para SARS-CoV-2; no hubo contactos positivos de casos con Ct>30. La cantidad de contactos positivos de casos con Ct<20 fue significativamente mayor que la de casos con Ct>20. Las muestras con Ct<20 se asociaron a una carga viral estimada de entre uno a cuatro órdenes de magnitud de diferencia con los rangos de Ct>20. Un 13,7% de contactos positivos fueron casos con Ct<20. De las muestras positivas confirmadas por PCR, correspondientes a la semana epidemiológica 1 de 2021 (SE1), sólo un 19,35% correspondían a muestras con Ct<20 y un 50,7% con Ct entre 20 y 30. Estos datos muestran un incremento de sólo un 3,7% de casos detectados. El esfuerzo por parte del sistema de salud pública para esta estrategia, con bajo poder predictivo, puede tener un efecto negativo para el cumplimiento del aislamiento de los contactos y podría generar una demora en los resultados de los casos sospechosos, sin aportar significativamente en el control de la pandemia.

Abstract The detection of SARS-CoV-2 and its implication in the diagnosis of COVID-19 have been highly debated in the pandemic. The objective of this study was to evaluate the cost/benefit of detecting SARS-CoV-2 in asymptomatic close contacts (CC) using different molecular diagnostic tests. A total of 51 CC of people with a diagnosis of SARS-CoV-2 confirmed by RTqPCR, classified by the cycle threshold (Ct) (<20, between 20 and 30 and >30), were studied in public hospitals in the Province of Buenos Aires. Of the total contacts studied, 15.7% were confirmed for SARS-CoV-2; there were no positive contacts of cases with Ct>30 positive. The number of positive contacts of cases with Ct<20 was significantly higher than that of cases with Ct>20. Samples with Ct<20 were associated with an estimated viral load of one to four orders of magnitude difference with Ct ranges >20. A total of 13.7% of positive close contacts were from cases with Ct<20. When studying positive samples with confirmed diagnosis by PCR, corresponding to 1 epidemiological week of 2021 (EW1), only 19.35% corresponded to samples with Ct<20 and 50.7% with Ct between 20 and 30. From these data it is shown that with the CC test only 3.7% of the cases were detected. The effort by the public health system for this strategy, with low predictive power, may have a negative effect on the fulfillment of the isolation of contacts and could generate a delay in the results of suspected cases, without contributing significantly to controlling the pandemic.

Resumo A detecção do SARS-CoV-2 e seu envolvimento no diagnóstico da COVID-19 têm sido muito discutidos durante a pandemia. O objetivo desse estudo foi avaliar a relação custo/benefício na detecção de SARSCoV- 2 em casos de contatos próximos assintomático (CP), por meio do uso de diferentes testes de diagnóstico molecular. Foram estudados 51 casos de CP de pessoas com diagnóstico de SARS-CoV-2 confirmado pelo RTqPCR, sendo classificados pelo limiar de ciclos (Ct) (<20, entre 20 e 30 e >30), em hospitais públicos da província de Buenos Aires. Do total de contatos estudados, 15,7% foram confirmados para SARS-CoV-2, não houve contatos positivos de casos com Ct>30. O número de contatos positivos de casos com Ct<20, foi significativamente maior que os casos com Ct>20. As amostras com Ct<20 foram associadas a uma carga viral estimada de uma a quatro ordens de magnitude de diferença com os intervalos de Ct>20. Dos casos positivos, 13,7% foram com Ct<20. Das amostras positivas confirmadas por PCR, correspondentes à semana epidemiológica 1 de 2021 (SE1), apenas 19,35% correspondiam a amostras com Ct>20 e 50,7% com Ct entre 20 e 30. Esses dados mostram incremento de apenas 3,7% de casos detectados. O esforço por parte do sistema de saúde pública para essa estratégia, com baixo poder preditivo, pode ter um efeito negativo no cumprimento do isolamento dos contatos e poderia gerar uma demora nos resultados dos casos suspeitos, sem contribuir significativamente para o controle da pandemia.

COVID-19: epidemiología, virología y transmisibilidad / COVID-19: epidemiology, virology, and transmissibility

Hasta diciembre del 2019, seis tipos de coronavirus ya estaban identificados como generadores de enfermedad en humanos, destacándose dos brotes epidemiológicos anteriores: SARS-CoV en 2002 y MERS-CoV en 2012. El nuevo agente infeccioso que causó la pandemia de 2019 se denominó SARS-CoV-2, el que se manifiesta como un síndrome respiratorio agudo severo (CO-VID-19). Al respecto, el 30 de enero del 2020, la Organización Mundial de la Salud (OMS) decretó la emergencia sanitaria. El propósito de esta revisión fue analizar el contexto epidemio-lógico alrededor del SARS-CoV-2, mediante una búsqueda bibliográfica en las bases de datos científicas como: PubMed Central, LILACS y Google académico. Se concluyó que el SARS-CoV-2 es altamente transmisible, con una tasa de letalidad en Ecuador del 8,59%.

Six types of coronaviruses were already identified as generators of disease in humans as of 2019, with two previous epidemiological outbreaks standing out: SARS-CoV in 2002 and MERS-CoV in 2012. The new infectious agent that caused the 2019 pandemic was called SARS -CoV-2, which manifests as a severe acute respiratory syndrome (COVID-19). In this regard, on January 30, 2020, the World Health Organization decreed the health emergency. The purpose of this review was to analyze the epidemiological context around SARS-CoV-2 through a bibliographic review in scientific databases such as: PubMed Central, LILACS and Google Scholar. It was concluded that SARS-CoV-2 is highly transmissible, with a fatality rate in Ecuador of 8.59%.

Alternative workflow for COVID-19 diagnosis using direct RT-PCR screening

Objective: COVID-19 is presently the most serious public health concern and diagnosis is a principal tool for controlling and monitoring the spread of the disease. This study aimed to evaluate the efficiency of direct RT-PCR (dRT-PCR) for detection of SARS-CoV-2. Methods: Twenty-seven nasopharyngeal swabs from symptomatic individuals were evaluated. Standard RT-PCR was conducted, and for dRT-PCR the samples were preheated before amplification. Results: Positive agreement was 63.2% and negative agreement was 100%, being moderately in accord. Conclusion: dRT-PCR may be an alternative for screening symptomatic patients and a reliable option during an eventual shortage of viral RNA purification kits.

Objetivo: A COVID-19 é atualmente um sério problema de saúde pública e o diagnóstico é a principal ferramenta para controlar e monitorar a propagação da doença. Este estudo teve como objetivo avaliar a eficiência da RT-PCR direta (dRT-PCR) para detecção do SARS-CoV-2. Métodos: Vinte e sete amostras de swab nasofaríngeo de indivíduos sintomáticos foram avaliados. A RT-PCR padrão foi realizada e para a dRT-PCR as amostras foram pré-aquecidas antes da amplificação. Resultados: A concordância positiva foi de 63,2% e a concordância negativa foi de 100%, sendo moderadamente concordante. Conclusão: A dRT-PCR pode ser uma alternativa para a triagem de pacientes sintomáticos e uma opção confiável durante uma eventual escassez de kits de purificação de RNA viral.

Placental Sampling for Understanding Viral Infections - A Simplified Protocol for the COVID-19 Pandemic / Coleta placentária para entender infecções virais - Um protocolo simplificado para a pandemia de COVID-19

Abstract Objective The coronavirus disease 2019 (COVID-19) is a pandemic viral disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The impact of the disease among the obstetric population remains unclear, and the study of the placenta can provide valuable information. Adequate sampling of the placental tissue can help characterize the pathways of viral infections. Methods A protocol of placental sampling is proposed, aiming at guaranteeing representativity of the placenta and describing the adequate conservation of samples and their integrity for future analysis. The protocol is presented in its complete and simplified versions, allowing its implementation in different complexity settings. Results Sampling with the minimum possible interval from childbirth is the key for adequate sampling and storage. This protocol has already been implemented during the Zika virus outbreak. Conclusion A protocol for adequate sampling and storage of placental tissue is fundamental for adequate evaluation of viral infections on the placenta. During the COVID-19 pandemic, implementation of this protocol may help to elucidate critical aspects of the SARS-CoV-2 infection.

Resumo Objetivo A doença do novo coronavírus (COVID-19) é uma doença viral pandêmica causada pelo coronavírus da síndrome respiratória aguda 2 (SARS-CoV-2). O impacto da doença entre a população obstétrica ainda é incerto, e o estudo da placenta pode fornecer informações valiosas. Assim, a coleta adequada do tecido placentário pode ajudar a caracterizar algumas propriedades das infecções virais. Métodos Um protocolo de coleta placentária é proposto, objetivando a garantia de representatividade da placenta, descrevendo a maneira de conservação adequada das amostras, e visando garantir sua integridade para análises futuras. O protocolo é apresentado em suas versões completa e simplificada, permitindo sua implementação em diferentes configurações de infraestrutura. Resultados A amostragem com o intervalo mínimo possível do parto é essencial para coleta e armazenamento adequados. Esse protocolo já foi implementado durante a epidemia de vírus Zika. Conclusão Um protocolo para coleta e armazenamento adequados de tecido placentário é fundamental para a avaliação adequada de infecções virais na placenta. Durante a pandemia de COVID-19, a implementação deste protocolo pode ajudar a elucidar aspectos críticos da infecção por SARS-CoV-2.

SARS-CoV-2 Modelo de Inoculación en la Cavidad Oral. Revisión de la Literatura / SARS-CoV-2 Model of Inoculation in the Oral Cavity. Literature Review

RESUMEN: El virus SARS-CoV-2 ingresa al organismo de un individuo susceptible a través de la cavidad oral, nasal o de la mucosa conjuntival; busca ensamblarse por medio de su glicoproteína de superficie o espiga con los receptores de la enzima convertidora de angiotensina 2 que en boca los encontramos con mayor expresión en las células escamosas que recubren el epitelio lingual y las glándulas salivales, una vez que ingresa por medio de la activación de proteasas ingresa a la célula huésped para denudar su RNA viral, a diferencia de otros virus no necesita ir hasta el núcleo de tal forma que en el citoplasma inicia su replicación y utiliza los ribosomas del huésped para formar una gran cantidad de proteínas virales tanto estructurales como accesorias que le permita formar nuevos viriones potencialmente infecciosos; los estomatólogos deben tomar en cuenta esta vía de infección y extremar las medidas para disminuir su carga viral local en la cavidad oral y las barreras físicas de protección para el operador, el paciente y la ergonomía del consultorio.

ABSTRACT: SARS-CoV-2 virus enters the body of a susceptible individual through oral, nasal or conjunctival mucosa, seeking to bind to the spike glycoprotein surface through angiotensin-converting enzyme 2 receptors. These are found in the mouth with a higher expression in oral squamous cells that cover the lingual epithelium and salivary glands. Once proteolytic activation begins, it enters the host cell to denudate its viral RNA. In contrast with other viruses, it does not require nucleus access, and therefore replicates in the cytoplasm using the host's ribosomes to produce great amounts of both structural and accessory viral proteins. Since this generates new and potentially infectious virions, dentists must consider this route of infection and take extreme measures to decrease their viral load in the oral cavity. Physical protection barriers for the operator, the patient and the health and safety of the work place are critical in these cases.

The role of the World Health Organization country programs in the development of virology in Spain, 1951-1975 / El papel desempeñado por los programas país de la Organización Mundial de la Salud en el desarrollo de la virología en España, 1951-1975

Abstract Within the framework of recent historiography about the role of the World Health Organization (WHO) in modernizing public health and the multifaceted concept of global health, this study addresses the impact of the WHO's "country programs" in Spain from the time it was admitted to this organization in 1951 to 1975. This research adopts a transnational historical perspective and emphasizes attention to the circulation of health knowledge, practices, and people, and focuses on the Spain-0001 and Spain-0025programs, their role in the development of virology in Spain, and the transformation of public health. Sources include historical archives (WHO, the Spanish National Health School), various WHO publications, the contemporary medical press, and a selection of the Spanish general press.

Resumen En el marco de la reciente historiografía sobre el papel de la Organización Mundial de la Salud (OMS) en la modernización de la salud pública y el concepto multifacético de salud global, se estudia el papel de los llamados "programas país" de la OMS en España desde su admisión en 1951 hasta 1975. Adoptando perspectiva histórica transnacional y enfatizando el estudio de la circulación de personas, conocimientos y prácticas científico-sanitarias, nuestro análisis se centra en los programas España-0001 y España-0025, en evaluar su papel en el desarrollo de la virología en España y en la transformación de la salud pública. Nuestras fuentes vienen de archivos históricos (OMS, Escuela Nacional de Sanidad), publicaciones de la OMS, revistas médicas contemporáneas, y una selección de prensa general española.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Clinical features of coronavirus disease 2019 in children: a systemic review of severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019 / 中国当代儿科杂志

OBJECTIVE@#To systematically summarize the clinical features of coronavirus disease 2019 (COVID-19) in children.@*METHODS@#PubMed, Embase, Web of Science, The Cochrane Library, CNKI, Weipu Database, and Wanfang Database were searched for clinical studies on COVID-19 in children published up to May 21, 2020. Two reviewers independently screened the articles, extracted data, and assessed the risk of bias of the studies included. A descriptive analysis was then performed for the studies. Related indices between children with COVID-19 and severe acute respiratory syndromes (SARS) or Middle East respiratory syndrome (MERS) were compared.@*RESULTS@#A total of 75 studies were included, with a total of 806 children with COVID-19. The research results showed that the age of the children ranged from 36 hours after birth to 18 years, with a male-female ratio of 1.21 : 1. Similar to SARS and MERS, COVID-19 often occurred with familial aggregation, and such cases accounted for 74.6% (601/806). The children with COVID-19, SARS, and MERS had similar clinical symptoms, mainly fever and cough. Some children had gastrointestinal symptoms. The children with asymptomatic infection accounted for 17.9% (144/806) of COVID-19 cases, 2.5% (2/81) of SARS cases, and 57.1% (12/21) of MERS cases. The children with COVID-19 and MERS mainly had bilateral lesions on chest imaging examination, with a positive rate of lesions of 63.4% (421/664) and 26.3% (5/19) respectively, which were lower than the corresponding positive rates of viral nucleic acid detection, which were 99.8% and 100% respectively. The chest radiological examination of the children with SARS mainly showed unilateral lesion, with a positive rate of imaging of 88.9% (72/81), which was higher than the corresponding positive rate of viral nucleic acid detection (29.2%). Viral nucleic acid was detected in the feces of children with COVID-19 or SARS, with positive rates of 60.2% (56/93) and 71.4% (5/7) respectively. The children with COVID-19 had a rate of severe disease of 4.6% (31/686) and a mortality rate of 0.1% (1/806), the children with SARS had a rate of severe disease of 1.5% (1/68) and a mortality rate of 0%, and those with MERS had a rate of severe disease of 14.3% (3/21) and a mortality rate of 9.5% (2/21).@*CONCLUSIONS@#Children with COVID-19 have similar symptoms to those with SARS or MERS, mainly fever and cough. Asymptomatic infection is observed in all three diseases. Children with COVID-19 or SARS have milder disease conditions than those with MERS. COVID-19 in children often occurs with familial aggregation. Epidemiological contact history, imaging examination findings, and viral nucleic acid testing results are important bases for the diagnosis of COVID-19.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Management of a colon cancer patient infected with corona virus disease 2019 / 浙江大学学报·医学版

OBJECTIVE@#To explore the feasibility of surgical treatment for cancer patients complicated with corona virus disease 2019 (COVID-19).@*METHODS@#The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed.@*RESULTS@#The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice.@*CONCLUSIONS@#The case indicates that it may feasible to undergo radical tumor surgery for cancer patients with COVID-19 after the virus nucleic acid testing turns negative and more studies are needed to confirm this conclusion.

Follow-up testing of viral nucleic acid in discharged patients with moderate type of 2019 coronavirus disease (COVID-19) / 浙江大学学报·医学版

OBJECTIVE@#To investigate the clinical outcome of patients with moderate type of corona virus disease 2019 (COVID-19) after discharge by retesting viral nucleic acid.@*METHODS@#Seven patients with moderate COVID-19 met the discharge criteria enacted by National Health Commission were quarantine in hospital for 7 days, then continuously quarantined at home for 4 weeks after discharged. During the three weeks of quarantined period, the symptoms and signs were documented; and sputum or nasal swab and feces samples were collected to test SARS-COV-2 nucleic acid by RT-PCR method.@*RESULTS@#There were no symptoms and signs during the quarantine period in all 7 patients. However, respiratory swabs from 3 patients were confirmed positive of SARS-COV-2 nucleic acid at 5 to 7 days after they met the discharge criteria.@*CONCLUSIONS@#The study indicates that there is a relatively high incidence of positive viral nucleic acid in patients met the discharge criteria, and it is suggested that patients met the current discharge criteria should be quarantined in hospital for another 7 days and the follow-up viral testing is necessary.

Replication and transmission mechanisms of highly pathogenic human coronaviruses / 浙江大学学报·医学版

The three known human highly pathogenic coronaviruses are severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus, (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human highly pathogenic coronaviruses are composed of non-structural proteins, structural proteins and accessory proteins. Viral particles recognize host receptors via spike glycoprotein (S protein), enter host cells by membrane fusion, replicate in host cells through large replication-transcription complexes, and promote proliferation by interfering with and suppressing the host's immune response. Human highly pathogenic coronaviruses are hosted by humans and vertebrates. Viral particles are transmitted through droplets, contact and aerosols or likely through digestive tract, urine, eyes and other routes. This review discusses the mechanisms of proliferation and transmission of highly pathogenic human coronaviruses based on the results of existing research, providing basis for future study on interrupting the transmission and pathogenicity of human highly pathogenic coronaviruses.

Management of COVID-19: the Zhejiang experience / 浙江大学学报·医学版

The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as and , so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore,we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.