Host range and structural analysis of bat-origin RshSTT182/200 coronavirus binding to human ACE2 and its animal orthologs.

Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2 and show identical receptor-binding domains (RBDs). In this study, we determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. The binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 of 39 ACE2 orthologs, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2. Furthermore, RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry. Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus. Taken together, these findings indicate that RshSTT182/200 can potentially infect susceptible animals, but requires further evolution to obtain strong interspecies transmission abilities like SARS-CoV-2.

Aspectos básicos de la COVID-19 para el manejo desde atención primaria / Basic aspects of COVID-19 for management from primary care

El SARS-CoV-2 se transmite de persona a persona por inhalación o por el contacto con gotas y aerosoles respiratorios. El período de incubación mediano es 5,1 días. Fiebre, tos seca, disnea y fatiga, son los síntomas más comunes. Casi la mitad de los casos son asintomáticos. El espectro de la enfermedad varía desde cuadros leves (81%) a críticos (5%). La edad avanzada, el sexo masculino y las comorbilidades impactan negativamente sobre la gravedad y la mortalidad de la COVID-19. El diagnóstico de la patología aguda se realiza con pruebas de reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) o de detección antigénica. En pacientes hospitalizados, el remdesivir reduce el tiempo de recuperación. Los corticoides orales se recomiendan en casos graves o críticos que requieren oxigenoterapia o ventilación mecánica. La tromboprofilaxis se sugiere en todos los casos graves y no graves con riesgo trombótico alto. La antibioterapia se limita a pacientes de alta sospecha de sobreinfección bacteriana. Los casos leves-moderados y graves tras el alta hospitalaria deben monitorizarse clínicamente durante un período mínimo de dos semanas.(AU)

SARS-CoV-2 is transmitted from person to person by inhalation or contact with respiratory droplets and aerosols. The median incubation period is 5.1 days. Fever, dry cough, dyspnea and fatigue are the most common symptoms. Almost half of the cases are asymptomatic. The spectrum of disease varies from mild (81%) to critical (5%). Older age, male gender and comorbidities negatively impact on the severity and mortality of COVID-19. The diagnosis of acute COVID-19 is made with RT-PCR or antigenic detection tests. In hospital patients, remdesivir reduces recovery time. Oral steroids are recommended for severe or critical cases requiring oxygen therapy or mechanical ventilation. Thromboprophylaxis is recommended in all severe and non-severe cases with high thrombotic risk. Antibiotherapy is limited to cases of high suspicion of bacterial superinfection. Mild-moderate and severe cases after discharge from hospital should be clinically monitored for a minimum period of two weeks.(AU)

Live Q&A on pregnancy and childbirth during COVID-19. Ask your questions!

Pregnant women or recently pregnant women who are older, overweight, and have pre-existing medical conditions such as hypertension and diabetes seem to have an increased risk of developing severe COVID-19. When pregnant women develop severe disease, they also seem to more often require care in intensive care units than non-pregnant women of reproductive age. Due to changes in their bodies and immune systems, we know that pregnant women can be badly affected by some respiratory infections. It is therefore important that they take precautions to protect themselves against COVID-19, and report possible symptoms (including fever, cough or difficulty in breathing) to their healthcare provider. WHO will continue to review and update its information and advice as more evidence becomes available.

A comparative review of pathogenesis and host innate immunity evasion strategies among the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV).

COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has put the global public health at its highest threat around the world. Previous epidemic caused by the acute respiratory syndrome coronavirus (SARS-CoV) in 2002 is also considered since both the coronaviruses resulted in the similar clinical complications. The outbreak caused by the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 had a low rate of disease transmission and death cases. Modes of entry by MERS and SARS coronaviruses are similar to that of SARS-CoV-2, except MERS-CoV utilize different receptor. They all belong to the lineage C of ß-coronavirus. Based on the information from the previous reports, the present review is mainly focused on the mechanisms of disease progression by each of these viruses in association to their strategies to escape the host immunity. The viral entry is the first step of pathogenesis associated with attachment of viral spike protein with host receptor help releasing the viral RNA into the host cell. Models of molecular pathogenesis are outlined with virus strategies escaping the host immunity along with the role of various inflammatory cytokines and chemokines in the process. The molecular aspects of pathogenesis have also been discussed.

WHO's Science in 5 on COVID-19: children & COVID-19

Science in 5 series - episode 22 / Are the symptoms of COVID-19 different in children? Do the new variants impact children differently? What can parents do to keep children safe from COVID-19. WHO's Dr Maria Van Kerkhove explains in Science in 5.

Mechanisms of Coronavirus Nsp1-Mediated Control of Host and Viral Gene Expression.

Many viruses disrupt host gene expression by degrading host mRNAs and/or manipulating translation activities to create a cellular environment favorable for viral replication. Often, virus-induced suppression of host gene expression, including those involved in antiviral responses, contributes to viral pathogenicity. Accordingly, clarifying the mechanisms of virus-induced disruption of host gene expression is important for understanding virus-host cell interactions and virus pathogenesis. Three highly pathogenic human coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and SARS-CoV-2, have emerged in the past two decades. All of them encode nonstructural protein 1 (nsp1) in their genomes. Nsp1 of SARS-CoV and MERS-CoV exhibit common biological functions for inducing endonucleolytic cleavage of host mRNAs and inhibition of host translation, while viral mRNAs evade the nsp1-induced mRNA cleavage. SARS-CoV nsp1 is a major pathogenic determinant for this virus, supporting the notion that a viral protein that suppresses host gene expression can be a virulence factor, and further suggesting the possibility that SARS-CoV-2 nsp1, which has high amino acid identity with SARS-CoV nsp1, may serve as a major virulence factor. This review summarizes the gene expression suppression functions of nsp1 of CoVs, with a primary focus on SARS-CoV nsp1 and MERS-CoV nsp1.

La COVID-19: comunicado conjunto sobre el nuevo coronavirus y los perros y gatos / COVID-19. Joint statement on the new coronavirus and cats and dogs

El Centro Panamericano de Fiebre Aftosa y Salud Pública Veterinaria de la Organización Panamericana de la Salud / Organización Mundial de la Salud (PANAFTOSA-OPS/OMS) y la Protección Animal Mundial (PAM) comunican al público en general los aspectos referentes al COVID-19 y la relación con las mascotas (perros y gatos).

Genotype and phenotype of COVID-19: Their roles in pathogenesis.

COVID-19 is a novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China, and then pandemic. Based on its phylogenetic relationships and genomic structures the COVID-19 belongs to genera Betacoronavirus. Human Betacoronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) have many similarities, but also have differences in their genomic and phenotypic structure that can influence their pathogenesis. COVID-19 is containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. A typical CoV contains at least six ORFs in its genome. All the structural and accessory proteins are translated from the sgRNAs of CoVs. Four main structural proteins are encoded by ORFs 10, 11 on the one-third of the genome near the 3'-terminus. The genetic and phenotypic structure of COVID-19 in pathogenesis is important. This article highlights the most important of these features compared to other Betacoronaviruses.

Competências e regras / Coleção COVID-19 / Skills and rules / COVID-19 Collection

No Brasil, as competências e regras a que se submetem os entes federados e as diferentes instituições afetas ao direito à saúde, conformaram-se no conteúdo desse livro. As Comissões Intergestores do SUS, o Congresso Nacional e o Tribunal de Contas da União (TCU), os conselhos nacionais de Justiça (CNJ) e do Ministério Público (CNMP), agências reguladoras (Anvisa) e o Conselho Nacional de Saúde (CNS) exararam manifestações por estratégias e instrumentação diversa, descritas e analisadas. As estratégias de saúde digital e da comunicação em saúde estiveram sob avaliação, assim como o desempenho do Conass e das Secretarias Estaduais de Saúde (SES), em especial no quesito transparência das informações. Ainda nessa seara, os textos aqui compilados trouxeram ao debate questões relacionadas às transferências de recursos federais aos cofres estaduais, às requisições administrativas e aos dilemas que circundam o âmbito fiscal do SUS. Numa tentativa de agrupar os principais comandos, estão apresentados o rol de leis e atos administrativos, a normativa regulatória sanitária e a interpretação do poder judiciário acerca da legislação, especialmente sob o crivo da responsabilização dos gestores públicos. Quando iniciada a organização da Coleção COVID-19, a principal expectativa era que a disponibilização de seu conteúdo ocorresse num cenário em que as medidas de prevenção, controle e até mesmo mitigação tivessem apresentado as melhores respostas, no Brasil e no mundo. Mas, o recrudescimento do número de infectados e dos óbitos já é um fato. Novas medidas, não farmacológicas, dessa vez acompanhadas das campanhas de vacinação em vários países, já são realidade no âmbito dos territórios. Portanto, o tempo permitirá perceber outros tantos comandos normativos afetos à saúde pública no Brasil e no mundo, o que requererá atenção do leitor quanto à necessidade de pesquisa e atualização. Conforme já asseverado, os textos revelam as opiniões de seus autores, ainda que porventura divirjam das posições do Conass. Que os diferentes posicionamentos compilados no Volume 3 ­ Competências e Regras ­ sejam capazes de denotar limites e potencialidades para a gestão, bem como possam contribuir com aprendizados para o futuro!

Reflexões e futuro / Coleção COVID-19 / Reflections and future / COVID-19 Collection

A partir dos desafios para a efetivação do direito à saúde, o Volume 6 ­ Reflexões e Futuro ­ apresenta debates relacionados às questões ambientais, urbanas, das relações humano-natureza, das arboviroses ­ que juntos contribuem para a análise da conformação do futuro pós-pandemia. Nessa esteira seguem análises relacionadas à saúde pública, à sociedade brasileira, à infoestrutura como apoio às decisões estratégicas e a avaliação, como dispositivo potente para a gestão. Ainda em sede de desafios, o livro aborda a Vigilância Sanitária como elemento primordial para o enfrentamento das emergências em saúde pública e nesse escopo se insere o Programa Nacional de Imunizações (PNI), do Brasil. À títulos comparativos, há narrativas acerca do enfrentamento da pandemia nos países de língua portuguesa, especialmente Portugal, bem como no Canadá e no Quebec possibilitando aprendizados com as experiências de outros sistemas universais. A abordagem acerca das políticas governamentais de compras públicas, da imagem do SUS nos contextos, nas narrativas e para as pessoas são encerradas com reflexões sobre a cobertura sanitária enquanto valor e a reforma sanitária brasileira como necessidade atual. Ainda que esse levante editorial se encerre, por ora, no volume 6 da Coleção COVID-19, a pandemia continua e outros tantos elementos poderão ser percebidos, contextualizados e merecerão registro. O Conass envida agradecimentos aos que estiveram empenhados em registrar seus diferentes campos de observação: gestores, auditores, ministros, médicos, pesquisadores, farmacêuticos, cientistas sociais, juízes, antropólogos, promotores, advogados, cientistas de dados, administradores, professores, comunicadores e todos que contribuíram com a análise e possíveis aperfeiçoamentos da gestão estadual do SUS no enfrentamento das emergências sanitárias.

Reinfecção por COVID-19

Casos de reinfeção por SARS-CoV-2, embora sejam raros, estão sendo identificados em vários países, inclusive no Brasil. Neste vídeo, a equipe COVID19 DivulgAÇÃO Científica conversa com o infectologista Fernando Bellissimo, da Universidade de São Paulo, que explica as possíveis causas de reinfeção pelo novo coronavírus. Ele fala, também, sobre o primeiro caso registrado de reinfeção no Brasil.

Los Aerosoles Dentales a Propósito de la Pandemia por COVID-19 / Dental Aerosols in the Context of COVID-19 Pandemic

RESUMEN: La pandemia por COVID-19 ha hecho que la atención odontológica de rutina se suspenda. La causa principal es el pobre control del aerosol en la consulta dental. Los aerosoles liberados por el instrumental odontológico son esenciales para la remoción de los tejidos bucales enfermos. Sin embargo, al mezclarse con saliva o sangre contaminada, los aerosoles pueden diseminar microorganismos infectivos fuera de la boca del paciente. Existe evidencia de que el SARS-CoV-2 se encuentra en la saliva del 91,7 % de los sujetos enfermos. Este artículo presenta evidencias y reflexiones para el control del aerosol odontológico, las que podrían permitir aumentar la seguridad del ejercicio de la odontología durante la pandemia y pospandemia.

ABSTRACT: The COVID-19 pandemic has caused routine dental check-ups to be cancelled. The main cause is poor aerosol control in the dental office. Aerosols released by dental instruments are essential for the removal of diseased oral tissues. However, when mixed with saliva or contaminated blood, aerosols can spread infectious microorganisms out of the patient's mouth. In addition, SARS-CoV-2 has been detected in the self-collected saliva of 91.7 % of patients. This article presents evidence and reflections for the control of dental aerosol, which could allow increasing the safety of dental practice during the pandemic and post-pandemic.

SARS-CoV-2 y enfermedad tromboembólica venosa. No todo es nuevo / SARS-CoV-2 and venous thromboembolic disease. Not everything is new

El SARS-CoV-2, responsable de la pandemia, ha demostrado un alto potencial trombogénico y, a pesar de ser un virus de reciente aparición, evidencia una relación estrecha con mecanismos fisiopatológicos previamente descritos. La enfermedad tromboembólica venosa es una de sus complicaciones más frecuentes, cuya presencia es directamente proporcional al incremento en la mortalidad de estos pacientes. En el contexto del SARS-CoV-2, si bien las heparinas han mostrado superioridad frente a otros fármacos por su efecto antiinflamatorio añadido, no se logra un consenso sobre su dosificación en los diferentes escenarios y, en condiciones de alta hospitalaria, la elección de la droga más idónea y la duración de la profilaxis farmacológica también han generado controversias y discrepancias. Tras una revisión exhaustiva y basada en la literatura publicada tanto en la era COVID-19 como en años pasados, presentamos para su discusión la escala de coagulopatía inducida por sepsis (SIC) y el valor del dímero D como parámetros objetivos frente a las incertidumbres planteadas. Además, se sugiere el uso de escalas previamente validadas y manejadas para evaluar el riesgo tromboembólico venoso, el sangrado y las probabilidades de sospecha diagnóstica de trombosis venosa profunda y embolia pulmonar, las mismas que podrían ayudar a reducir sesgos subjetivos

SARS-CoV-2, responsible for the pandemic; has shown a high thrombogenic potential, but; despite being a newly emerging virus, it shows a close relationship with previously described pathophysiological mechanisms. Venous thromboembolic disease is the most frequent complication and it is directly proportional to the increase in mortality in these patients. In SARS-CoV-2 context, heparins have shown superiority over other drugs for their anti-inflammatory effect but there is not an established consensus about their dosage in different stages of the disease; moreover, at hospital discharge, the most suitable drug choice and pharmacological prophylaxis duration is controversial. After an exhaustive review and based in both, current COVID-19 era literature and the past years related scientific information, we propose sepsis-induced coagulopathy (SIC) score and D-dimer quantification as objective parameters; in addition, we suggest the use of previously validated scores to assess venous thromboembolic risk, bleeding and diagnostic suspicion of deep vein thrombosis and pulmonary embolism; these could help to reduce subjective bias and try to clear uncertainties about this topic

Epidemiología y fisiopatología de la COVID-19 / Epidemiology and physiopathology of COVID-19

Desde 2002, tras la epidemia de síndrome respiratorio agudo grave (SARS), expertos virólogos y epidemiólogos han alertado durante años de la posibilidad de una pandemia. En diciembre de 2019 se produjo un brote epidémico por un nuevo coronavirus, el SARS-CoV-2, que, a fecha de 2 de noviembre de 2020, ha causado 46.597.299 casos de infección en el mundo y 1.201.162 muertes. España es el segundo país con mayor incidencia de la Unión Europea, con 530,7 casos por 100.000 habitantes, con una tasa de letalidad del 4,5%. El SARS-CoV-2 es un virus de cadena simple de ácido ribonucleico de sentido positivo compactada en forma helicoidal por la proteína N, con una envoltura proteica donde destaca la proteína S, responsable de la entrada del virus en el citoplasma celular a través de la enzima conversora de la angiotensina 2. La actual revisión pretende realizar un resumen de los datos claves de la enfermedad que conocemos hasta este momento

Since 2002, after the Severe acute respiratory syndrome (SARS) epidemic, virologists and epidemiologists have warned for years of the possibility of a pandemic. In December 2019, there was an epidemic outbreak caused by a new coronavirus, SARS-CoV-2, which has caused 46,597,299 cases worldwide and 1,202,162 deaths. Spain is the second country with the highest incidence in the European Union with 530,7 cases per 100,000 inhabitants, with a fatality rate of 4,5%. SARS-CoV-2 is a positive-sense ribonucleic acid single chain virus helically compacted by protein N. Protein S is part of the envelope and responsible for the entry of the virus into the cell cytoplasm through the angiotensin converting enzyme 2. The current review is intended to summarize the key data of the disease that we know so far

Ciência em 5: COVID-19 Mitos x Ciência

O COVID -19 pode ser transmitido através da água? Ou mosquitos? A transmissão é afetada pelo clima? A Dra. Sylvie Briand destrói mitos populares sobre COVID-19 nesta edição da Science in 5, a WHO Scientific Conversations.

Dr Tedros on the long lasting symptoms of COVID-19

"Listening to Paul Garner, Martha Sibanda and Lyth Hishmeh share their experiences and array of symptoms, it reinforces what a dangerous virus COVID-19 is. Governments must recognise the long-term effects of the virus and ensure access to health services for those patients. Their stories reinforce how morally unconscionable and unfeasible the so called ‘natural herd immunity’ strategy is. Not only would it lead to millions more unnecessary deaths, it would also lead to a significant number of people facing a long road to full recovery. Herd immunity is only possible with safe and effective vaccines that are distributed equitably around the world. Until we have a vaccine, governments and people must do all that they can to suppress transmission, which is the best way to prevent post-COVID long-term effects." - Tedros Adhanom Ghebreyesus watch the entire press conference of 30 October 2020 here: https://youtu.be/sXsPHgdt3so

Immune suppression in the early stage of COVID-19 disease.

The outbreak of COVID-19 has become a worldwide pandemic. The pathogenesis of this infectious disease and how it differs from other drivers of pneumonia is unclear. Here we analyze urine samples from COVID-19 infection cases, healthy donors and non-COVID-19 pneumonia cases using quantitative proteomics. The molecular changes suggest that immunosuppression and tight junction impairment occur in the early stage of COVID-19 infection. Further subgrouping of COVID-19 patients into moderate and severe types shows that an activated immune response emerges in severely affected patients. We propose a two-stage mechanism of pathogenesis for this unusual viral infection. Our data advance our understanding of the clinical features of COVID-19 infections and provide a resource for future mechanistic and therapeutics studies.

STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters.

Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.