Molecular biology of coronaviruses: an overview of virus-host interactions and pathogenesis / Biología molecular de los coronavirus: una visión panorámica de las interacciones virus-hospedero y de la patogénesis

Abstract Coronaviruses (CoV) are enveloped, plus-strand RNA viruses that have the largest known RNA genomes and infect birds and mammals, causing various diseases. Human coronaviruses (HCoVs) were first identified in the mid-1960s and have been known to cause enteric or respiratory infections. In the last two decades, three HCoVs have emerged, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initiated the ongoing pandemic. SARS-CoV-2 causes a respiratory illness that presents as a mild upper respiratory disease but may result in acute respiratory distress syndrome, multi-organ failure and can be fatal, especially when underlying comorbidities are present. Children account for a low percentage of coronavirus disease 2019 (COVID-19) cases, with seemingly less severe disease. Most pediatric patients present mild or moderate symptoms or are asymptomatic. However, some cases may be severe. Therefore, SARS-CoV-2 infection and COVID-19 in pediatric patients must be studied in detail. This review describes general features of the molecular biology of CoVs and virus-host interactions that may be implicated in the pathogenesis of SARS-CoV-2.

Resumen Los coronavirus son virus envueltos de ARN de polaridad positiva, con los genomas más grandes que se conocen. Infectan aves y mamíferos, y causan una amplia variedad de enfermedades. Los coronavirus humanos se identificaron a mediados de la década de 1960 y se sabe que causan infecciones entéricas y respiratorias. En las últimas dos décadas han emergido tres coronavirus humanos pandémicos, incluido el coronavirus 2 del síndrome agudo respiratorio grave (SARS-CoV-2) que ha causado la pandemia actual. El SARS-CoV-2 produce enfermedad respiratoria que se presenta con padecimientos moderados de las vías respiratorias altas, pero puede resultar en síndrome respiratorio agudo, falla multiorgánica y muerte, en especial en casos con morbilidad subyacente. Los casos de COVID-19 en niños representan un porcentaje bajo y con síntomas menos graves de la enfermedad. La mayoría de los pacientes pediátricos son asintomáticos o presentan enfermedad leve o moderada; sin embargo, también en niños la enfermedad puede ser grave, por lo que la infección con SARS-CoV-2 y la COVID-19 en pacientes pediátricos deben estudiarse con detalle. En esta revisión se describen las características generales de la biología molecular de los coronavirus y de las interacciones virus-hospedero que se conocen para los coronavirus humanos identificados previamente, y que podrían estar implicados en la patogénesis del SARS-CoV-2.

Características de los coronavirus, origen del SARS-CoV-2, características estructurales, proteínas y factores de virulencia, variantes genéticas / Characteristics of coronaviruses, origin of SARS-CoV-2, characteristics structural, proteins and factors of virulence, genetic variants

Coronaviruses (CoVs) were identified in 1937, they were considered innocuous viruses until the appearance of three highly pathogenic variants, SARS-CoV, MERS-CoV and SARS-CoV-2 causing the current pandemic of Covid-19, so far it is known that its origin is zoonotic, the main reservoir could be bats considering the high homology of CoVs that inhabit this species. Its transmissibility is much higher than that of previous CoVs, possibly in the process of natural selection; it has acquired some or all the mutations necessary for a much more efficient transmission in our species. This condition is specifically attributed to unique characteristics of the SARS-CoV-2 Spike protein that allow it greater affinity and therefore greater infectivity by binding to the angiotensin receptor 2 (ACE-2) present in the host cells. Since the Covid-19 outbreak began at the end of 2019, more than 1,500 mutations have been detected throughout the SARS-CoV-2 genome, however the most significant are those that occur near or in the receptor binding domain (RBD) that could provide variations between 4x to 100x greater infectivity, such is the case of the new variants identified in the United Kingdom, South Africa, Brazil and Japan that force us to take extreme preventive measures and continue research to elucidate strategies to combat the current crisis. (AU)

COVID-19 en la terapia intensiva: Análisis de la experiencia durante el primer mes de la pandemia / COVID-19 in the intensive care unit. Analysis of the experience during the first month of pandemic

Se trata de un análisis de características clínicas, hallazgos radiológicos, variables de laboratorio y mecánica respiratoria en pacientes con enfermedad por coronavirus 2019 (COVID-19) durante el primer mes de la pandemia en Buenos Aires. Es un estudio descriptivo de casos, de un solo centro. Se incluyeron todos los casos confirmados de COVID-19 internados en la unidad de terapia intensiva de adultos (UTIA) del Hospital Italiano de Buenos Aires. Todos los casos se confirmaron por reacción en cadena de la polimerasa con transcriptasa inversa. Un total de 7 pacientes con COVID-19 fueron atendidos en la UTIA. La mediana de edad fue de 71 años (intervalos intercuartílicos: 52-75), 4 hombres y 3 mujeres. Las manifestaciones clínicas más comunes fueron fiebre (7), tos (5), astenia (4) y disnea (3). Entre los hallazgos radiológicos, cinco de ellos mostraron opacidades intersticiales y un paciente consolidación pulmonar bilateral. Cinco requirieron ventilación mecánica invasiva y múltiples sesiones de decúbito prono. Ninguno murió durante la hospitalización, aunque aún tres permanecen en UCI.

This is an analysis of clinical characteristics, images findings, laboratory variables and respiratory mechanics in patients with coronavirus disease 2019 (COVID-19) during the first month of the pandemic outbreak in Buenos Aires. In this descriptive case study of a single-centre, we included all confirmed cases of COVID-19 hospitalized in intensive care unit (ICU). All cases were confirmed by reverse transcription polymerase chain reaction. A total of 7 patients with confirmed COVID-19 were referred to out ICU. The median age was 71 years (interquartile range 52-75), including 4 men and 3 women. Patients most common clinical manifestations were fever (7), cough (5), asthenia (4) and shortness of breath (3). Among the radiological findings, five of them showed interstitial opacities and one patient had bilateral pulmonary consolidation. Five required invasive mechanical ventilation and multiple prone sessions. None died during hospitalization, although three still remain in the ICU. According to imaging examination, 71.4% showed interstitial opacities and one patient bilateral consolidation. Five patients required invasive mechanical ventilation and multiple prone sessions. None of them died during hospitalization, although three still remain in the ICU.

Concordance of chest ct and nucleic acid testing in diagnosing coronavirus disease outside its district of origin (Wuhan, China)

OBJECTIVES: This study aimed to determine the concordance between CT and nucleic acid testing in diagnosing coronavirus disease (COVID-19) outside its district of origin (Wuhan, China). METHODS: Twenty-three consecutive patients with COVID-19, confirmed by nucleic acid testing, were enrolled from two designated hospitals outside the district of disease origin. We collected clinical, laboratory, and CT data and assessed the concordance between CT manifestations and nucleic acid test results by comparing the percentage of patients with and without abnormal CT findings. Furthermore, using Chi-square tests, we analyzed the differences in CT manifestations between patients with and without an exposure history or symptoms. RESULTS: Multiple ground-glass opacities (GGOs), with or without consolidation, were observed on the initial CT scans of 19 patients (82.6%), whereas the remaining 4 (17.4%) showed no CT abnormalities, indicating that the initial chest CT findings were not entirely concordant with the nucleic acid test results in diagnosing COVID-19. Among the latter 4 patients, we observed multiple GGOs with and without consolidation in 2 patients on the follow-up chest CT scans taken on days 7 and 14 after admission, respectively. The remaining 2 patients showed no abnormalities on the follow-up CT scans. Furthermore, abnormal CT findings were found more frequently in patients who had been exposed to COVID-19 in its district of origin than in those who had not been exposed and in symptomatic patients than in asymptomatic patients (all p<0.05). CONCLUSIONS: Patients with positive results on nucleic acid testing may or may not have the abnormal CT manifestations that are frequently found in symptomatic patients with a history of exposure to the district of COVID-19 origin.

Abdominal symptoms as initial manifestation of COVID-19: a case series / Sintomas abdominais como manifestação inicial da COVID-19: uma série de casos

ABSTRACT The COVID-19 became a pandemic in early 2020. It was found, at first, that the main manifestations of this new virus occur through respiratory and constitutional symptoms. Therefore, chest tomography was elected as the best imaging test to assess the extent of pulmonary involvement and as a good prognostic predictor for the disease. However, as new studies were produced, the gastrointestinal involvement of COVID-19 becomes more evident, with reports from patients who manifested mainly or only gastrointestinal symptoms in the course of the disease. Thus, in some cases, the initial investigation is carried out at the emergency department with an abdominal computed tomography. We report a case series of ten patients who came to the emergency department of our institution with a chief gastrointestinal complaint, and were initially submitted to an abdominal computed tomography as the first investigation. Although most of the patients did not have significant changes in the abdominal images, most reported patients had pulmonary findings visualized at the lung bases, which were later designated as typical COVID-19 pulmonary findings on chest computed tomography. Only one patient had atypical COVID-19 lung changes on chest computed tomography. All patients had a positive real-time polymerase chain reaction for COVID-19. It is imperative to alert radiologists, especially abdominal radiologists, with the possibility of COVID-19 isolated gastrointestinal symptoms. Besides, it must become a habit to radiologists to assess the pulmonary basis on abdominal scans, a site commonly affected by the new coronavirus.

RESUMO A COVID-19 foi declarada uma pandemia no início de 2020. Constatou-se, inicialmente, que as principais manifestações desse novo vírus ocorrem por meio de sintomas respiratórios e constitucionais. A tomografia do tórax foi eleita o exame de imagem para avaliar a extensão do comprometimento pulmonar e como um fator preditivo do prognóstico para a doença. No entanto, à medida que novos estudos são produzidos, o envolvimento gastrointestinal da COVID-19 torna-se mais evidente, com relatos de pacientes que manifestaram principalmente ou apenas sintomas gastrointestinais no decorrer da doença. Em alguns casos, a investigação inicial é realizada no pronto-socorro, com tomografia computadorizada do abdome. Relatamos uma série de casos de dez pacientes que compareceram ao serviço de emergência da instituição com uma queixa principal gastrointestinal e foram submetidos inicialmente a uma tomografia computadorizada de abdome como primeira investigação. Embora a maioria dos pacientes não tenha apresentado alterações significativas nas imagens abdominais, eles apresentaram achados pulmonares visualizados nas bases pulmonares, que depois foram caracterizadas como achados pulmonares típicos de COVID-19 nas tomografias de tórax subsequentes. Apenas um paciente apresentou achados atípicos para COVID-19 na tomografia. Todos os pacientes tiveram reação em cadeia da polimerase em tempo real positiva para o novo coronavírus. É muito importante alertar os radiologistas, principalmente os radiologistas abdominais, da possibilidade de sintomas gastrointestinais isolados no contexto da COVID-19. Além disso, deve ser um hábito para todos os radiologistas avaliar as bases pulmonares nas tomografias de abdome, local comumente afetado pela COVID-19.

The diagnostic process of covid-19 in the emergency department: laboratory and imaging methods

SUMMARY OBJECTIVES The 2019 Novel coronavirus disease puts a serious burden on the health system. Therefore, the detection of particularly serious patients at an early stage is extremely important in terms of controlling the outbreak and improving the prognosis. We investigated the role of inflammatory markers studied in patients suspected of COVID-19 at an emergency department in predicting PCR and CT results. METHODS This retrospective study was carried out with 133 patients who were admitted between 13 March and 1st April 2020 with suspicion of COVID-19. The patients were divided into four groups according to CT and RT-PCR results and evaluated. RESULTS Considering all patients, no specific findings were found in the hematological and biochemical values of patients in the laboratory analyses. Although all of the results remained within the reference range, there was a significant difference in white blood cell, neutrophil, platelet, and lymphocyte values when the groups were compared [p = 0.000; p = 0.004; p = 0.022; p = 0.023]. CONCLUSION Laboratory is not specific enough in the pre-diagnosis. In addition, this result does not alter with PCR or CT positivity. However, minimal changes observed in laboratory results may be partially guiding in patients in whom both PCR and CT are positive.

RESUMO OBJETIVOS A nova doença de coronavírus de 2019 coloca um fardo sério para o sistema de saúde. Portanto, a detecção de pacientes especialmente graves em um estágio inicial é extremamente importante em termos de controle do surto e melhoria do prognóstico. Investigamos o papel dos marcadores inflamatórios estudados em pacientes suspeitos de COVID-19 no pronto-socorro na previsão de resultados de PCR e CT. MÉTODOS Este estudo retrospectivo foi realizado entre 133 pacientes que foram admitidos entre 13 de março e 1o de abril de 2020 com suspeita de COVID-19. Os pacientes foram divididos em quatro grupos de acordo com os resultados da TC e RT-PCR e avaliados. RESULTADOS Considerando todos os pacientes, não foram encontrados achados específicos nos valores hematológicos e bioquímicos dos pacientes em análises laboratoriais. Embora todos os resultados tenham permanecido dentro do intervalo de referência, houve uma diferença significativa nos valores de glóbulos brancos, neutrófilos, plaquetas e linfócitos quando os grupos foram comparados [p = 0,000; p = 0,004; p = 0,022; p = 0,023]. CONCLUSÃO O laboratório não é suficientemente específico no pré-diagnóstico. Além disso, este resultado não se altera com a positividade para PCR ou CT. No entanto, alterações mínimas observadas nos resultados laboratoriais podem ser parcialmente norteadoras em pacientes com PCR e CT positivos.

Possible Transfusion-Related Acute Lung Injury Following Convalescent Plasma Transfusion in a Patient With Middle East Respiratory Syndrome

No abstract available.

Respiratory Viral Infections after Hematopoietic Stem Cell Transplantation in Children

This study was performed to characterize respiratory viral infections in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Study samples included 402 respiratory specimens obtained from 358 clinical episodes that occurred in the 116 children of the 175 consecutive HSCT cohort at Seoul National University Children's Hospital, Korea from 2007 to 2010. Multiplex reverse-transcription polymerase chain reactions were performed for rhinovirus, respiratory syncytial virus (RSV), parainfluenza viruses (PIVs), adenovirus, human coronavirus (hCoV), influenza viruses and human metapneumovirus. Viruses were identified in 89 clinical episodes that occurred in 58 patients. Among the 89 clinical episodes, frequently detected viruses were rhinovirus in 25 (28.1%), RSV in 23 (25.8%), PIV-3 in 16 (18.0%), adenovirus in 12 (13.5%), and hCoV in 10 (11.2%). Lower respiratory tract infections were diagnosed in 34 (38.2%). Neutropenia was present in 24 (27.0%) episodes and lymphopenia was in 31 (34.8%) episodes. Sixty-three percent of the clinical episodes were hospital-acquired. Three patients died of respiratory failure caused by respiratory viral infections. Respiratory viral infections in pediatric patients who have undergone HSCT are common and are frequently acquired during hospitalization. Continuous monitoring is required to determine the role of respiratory viruses in immunocompromised children and the importance of preventive strategies.

A coronavirus detected in the vampire bat Desmodus rotundus

This article reports on the identification of a group 2 coronavirus (BatCoV DR/2007) in a Desmodus rotundus vampire bat in Brazil. Phylogenetic analysis of ORF1b revealed that BatCoV DR/2007 originates from a unique lineage in the archetypical group 2 coronaviruses, as described for bat species elsewhere with putative importance in Public Health.