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1.
Recurso de Internet en Portugués | LIS - Localizador de Información en Salud | ID: lis-48245

RESUMEN

A Organização Mundial de Saúde (OMS) e os centros de pesquisa de todo o mundo – inclusive na Universidade Federal de Juiz de Fora (UFJF) estão investigando as mudanças constantes do novo coronavírus podem ocasionar algum impacto na eficácia das vacinas desenvolvidas, na capacidade de transmissão do Sars-CoV-2 e no desenvolvimento de quadros clínicos mais graves da Covid-19. A ciência tem se esforçado na busca diária de respostas e até o momento, provou ser seguro e aconselhável tomar qualquer uma das vacinas aprovadas pelas agências de vigilância sanitária ao redor do mundo e que, independentemente da variante do novo coronavírus, a forma de se prevenir da doença é a mesma: uso de máscara, lavagem correta das mãos com sabão ou álcool em gel 70, distanciamento social e vacina.


Asunto(s)
Infecciones por Coronavirus , Neumonía Viral , Betacoronavirus/genética
3.
Hum Genomics ; 15(1): 26, 2021 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-33962680

RESUMEN

BACKGROUND: Mathematical approaches have been for decades used to probe the structure of DNA sequences. This has led to the development of Bioinformatics. In this exploratory work, a novel mathematical method is applied to probe the DNA structure of two related viral families: those of coronaviruses and those of influenza viruses. The coronaviruses are SARS-CoV-2, SARS-CoV-1, and MERS. The influenza viruses include H1N1-1918, H1N1-2009, H2N2-1957, and H3N2-1968. METHODS: The mathematical method used is the slow feature analysis (SFA), a rather new but promising method to delineate complex structure in DNA sequences. RESULTS: The analysis indicates that the DNA sequences exhibit an elaborate and convoluted structure akin to complex networks. We define a measure of complexity and show that each DNA sequence exhibits a certain degree of complexity within itself, while at the same time there exists complex inter-relationships between the sequences within a family and between the two families. From these relationships, we find evidence, especially for the coronavirus family, that increasing complexity in a sequence is associated with higher transmission rate but with lower mortality. CONCLUSIONS: The complexity measure defined here may hold a promise and could become a useful tool in the prediction of transmission and mortality rates in future new viral strains.


Asunto(s)
Betacoronavirus/clasificación , Betacoronavirus/genética , Virus de la Influenza A/clasificación , Virus de la Influenza A/genética , Modelos Genéticos , Betacoronavirus/fisiología , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Evolución Molecular , Humanos , Virus de la Influenza A/fisiología , Gripe Humana/mortalidad , Gripe Humana/transmisión , Gripe Humana/virología , Análisis de Secuencia de ADN , Especificidad de la Especie , Factores de Tiempo
4.
Virol J ; 18(1): 89, 2021 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-33931105

RESUMEN

BACKGROUND: A novel coronavirus (SARS-CoV-2) emerging has put global public health institutes on high alert. Little is known about the epidemiology and clinical characteristics of human coronaviruses infections in relation to infections with other respiratory viruses. METHODS: From February 2017 to December 2019, 3660 respiratory samples submitted to Zhejiang Children Hospital with acute respiratory symptoms were tested for four human coronaviruses RNA by a novel two-tube multiplex reverse transcription polymerase chain reaction assays. Samples were also screened for the occurrence of SARS-CoV-2 by reverse transcription-PCR analysis. RESULTS: Coronavirus RNAs were detected in 144 (3.93%) specimens: HCoV-HKU1 in 38 specimens, HCoV-NL63 in 62 specimens, HCoV-OC43 in 38 specimens and HCoV-229E in 8 specimens. Genomes for SARS-CoV-2 were absent in all specimens by RT-PCR analysis during the study period. The majority of HCoV infections occurred during fall months. No significant differences in gender, sample type, year were seen across species. 37.5 to 52.6% of coronaviruses detected were in specimens testing positive for other respiratory viruses. Phylogenic analysis identified that Zhejiang coronaviruses belong to multiple lineages of the coronaviruses circulating in other countries and areas. CONCLUSION: Common HCoVs may have annual peaks of circulation in fall months in the Zhejiang province, China. Genetic relatedness to the coronaviruses in other regions suggests further surveillance on human coronaviruses in clinical samples are clearly needed to understand their patterns of activity and role in the emergence of novel coronaviruses.


Asunto(s)
COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa Multiplex/métodos , Infecciones del Sistema Respiratorio/virología , SARS-CoV-2/genética , Adolescente , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , COVID-19/complicaciones , COVID-19/genética , COVID-19/fisiopatología , Niño , Preescolar , China/epidemiología , Coronavirus/genética , Coronavirus/aislamiento & purificación , Coronavirus Humano 229E/genética , Coronavirus Humano 229E/aislamiento & purificación , Coronavirus Humano NL63/genética , Coronavirus Humano NL63/aislamiento & purificación , Coronavirus Humano OC43/genética , Coronavirus Humano OC43/aislamiento & purificación , Femenino , Hospitalización , Humanos , Lactante , Recién Nacido , Masculino , Filogenia , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/etiología , SARS-CoV-2/aislamiento & purificación , Glicoproteína de la Espiga del Coronavirus/genética
5.
Nat Commun ; 12(1): 2642, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33976134

RESUMEN

Despite its clinical importance, the SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 biology. We use comparative genomics to provide a high-confidence protein-coding gene set, characterize evolutionary constraint, and prioritize functional mutations. We select 44 Sarbecovirus genomes at ideally-suited evolutionary distances, and quantify protein-coding evolutionary signatures and overlapping constraint. We find strong protein-coding signatures for ORFs 3a, 6, 7a, 7b, 8, 9b, and a novel alternate-frame gene, ORF3c, whereas ORFs 2b, 3d/3d-2, 3b, 9c, and 10 lack protein-coding signatures or convincing experimental evidence of protein-coding function. Furthermore, we show no other conserved protein-coding genes remain to be discovered. Mutation analysis suggests ORF8 contributes to within-individual fitness but not person-to-person transmission. Cross-strain and within-strain evolutionary pressures agree, except for fewer-than-expected within-strain mutations in nsp3 and S1, and more-than-expected in nucleocapsid, which shows a cluster of mutations in a predicted B-cell epitope, suggesting immune-avoidance selection. Evolutionary histories of residues disrupted by spike-protein substitutions D614G, N501Y, E484K, and K417N/T provide clues about their biology, and we catalog likely-functional co-inherited mutations. Previously reported RNA-modification sites show no enrichment for conservation. Here we report a high-confidence gene set and evolutionary-history annotations providing valuable resources and insights on SARS-CoV-2 biology, mutations, and evolution.


Asunto(s)
COVID-19/virología , Genoma Viral/genética , Mutación , SARS-CoV-2/genética , Betacoronavirus/clasificación , Betacoronavirus/genética , Codón , Evolución Molecular , Genes Virales , Aptitud Genética , Variación Genética , Sistemas de Lectura Abierta , Filogenia , Glicoproteína de la Espiga del Coronavirus/genética , Proteínas Virales/genética
8.
Int J Mol Sci ; 22(3)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33525632

RESUMEN

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of Betacoronavirus that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic Betacoronaviruses include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family. We include information on their structures, functions, and participation in pathogenesis. While the shared proteins among the different coronaviruses may vary in structure and function, they all seem to be multifunctional, a common theme interconnecting these viruses. Many transmembrane proteins encoded within the SARS-CoV-2 genome play important roles in the infection cycle while others have functions yet to be understood. We compare the various structural and nonstructural proteins within the Coronaviridae family to elucidate potential overlaps and parallels in function, focusing primarily on the transmembrane proteins and their influences on host membrane arrangements, secretory pathways, cellular growth inhibition, cell death and immune responses during the viral replication cycle. We also offer bioinformatic analyses of potential viroporin activities of the membrane proteins and their sequence similarities to the Envelope (E) protein. In the last major part of the review, we discuss complement, stimulation of inflammation, and immune evasion/suppression that leads to CoV-derived severe disease and mortality. The overall pathogenesis and disease progression of CoVs is put into perspective by indicating several stages in the resulting infection process in which both host and antiviral therapies could be targeted to block the viral cycle. Lastly, we discuss the development of adaptive immunity against various structural proteins, indicating specific vulnerable regions in the proteins. We discuss current CoV vaccine development approaches with purified proteins, attenuated viruses and DNA vaccines.


Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/metabolismo , Proteínas de la Matriz Viral/metabolismo , Animales , Betacoronavirus/genética , Betacoronavirus/inmunología , COVID-19/inmunología , COVID-19/metabolismo , COVID-19/patología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Genoma Viral , Interacciones Huésped-Patógeno , Humanos , Evasión Inmune , Mapas de Interacción de Proteínas , SARS-CoV-2/genética , SARS-CoV-2/inmunología , SARS-CoV-2/fisiología , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/inmunología , Internalización del Virus , Replicación Viral
9.
PLoS One ; 16(2): e0246901, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33596252

RESUMEN

The MERS-CoV, SARS-CoV, and SARS-CoV-2 are highly pathogenic viruses that can cause severe pneumonic diseases in humans. Unfortunately, there is a non-available effective treatment to combat these viruses. Domain-motif interactions (DMIs) are an essential means by which viruses mimic and hijack the biological processes of host cells. To disentangle how viruses achieve this process can help to develop new rational therapies. Data mining was performed to obtain DMIs stored as regular expressions (regexp) in 3DID and ELM databases. The mined regexp information was mapped on the coronaviruses' proteomes. Most motifs on viral protein that could interact with human proteins are shared across the coronavirus species, indicating that molecular mimicry is a common strategy for coronavirus infection. Enrichment ontology analysis for protein domains showed a shared biological process and molecular function terms related to carbon source utilization and potassium channel regulation. Some of the mapped motifs were nested on B, and T cell epitopes, suggesting that it could be as an alternative way for reverse vaccinology. The information obtained in this study could be used for further theoretic and experimental explorations on coronavirus infection mechanism and development of medicines for treatment.


Asunto(s)
Betacoronavirus/metabolismo , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Imitación Molecular/fisiología , Dominios y Motivos de Interacción de Proteínas/inmunología , Betacoronavirus/genética , COVID-19/metabolismo , COVID-19/virología , Infecciones por Coronavirus/genética , Bases de Datos Genéticas , Interacciones Huésped-Patógeno , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Coronavirus del Síndrome Respiratorio de Oriente Medio/metabolismo , Dominios Proteicos , Dominios y Motivos de Interacción de Proteínas/genética , Proteoma , Virus del SRAS/genética , Virus del SRAS/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Proteínas Virales/metabolismo
10.
Sci Rep ; 11(1): 4108, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33602998

RESUMEN

In December 2019, rising pneumonia cases caused by a novel ß-coronavirus (SARS-CoV-2) occurred in Wuhan, China, which has rapidly spread worldwide, causing thousands of deaths. The WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern, since then several scientists are dedicated to its study. It has been observed that many human viruses have codon usage biases that match highly expressed proteins in the tissues they infect and depend on the host cell machinery for the replication and co-evolution. In this work, we analysed 91 molecular features and codon usage patterns for 339 viral genes and 463 human genes that consisted of 677,873 codon positions. Hereby, we selected the highly expressed genes from human lung tissue to perform computational studies that permit to compare their molecular features with those of SARS, SARS-CoV-2 and MERS genes. The integrated analysis of all the features revealed that certain viral genes and overexpressed human genes have similar codon usage patterns. The main pattern was the A/T bias that together with other features could propitiate the viral infection, enhanced by a host dependant specialization of the translation machinery of only some of the overexpressed genes. The envelope protein E, the membrane glycoprotein M and ORF7 could be further benefited. This could be the key for a facilitated translation and viral replication conducting to different comorbidities depending on the genetic variability of population due to the host translation machinery. This is the first codon usage approach that reveals which human genes could be potentially deregulated due to the codon usage similarities between the host and the viral genes when the virus is already inside the human cells of the lung tissues. Our work leaded to the identification of additional highly expressed human genes which are not the usual suspects but might play a role in the viral infection and settle the basis for further research in the field of human genetics associated with new viral infections. To identify the genes that could be deregulated under a viral infection is important to predict the collateral effects and determine which individuals would be more susceptible based on their genetic features and comorbidities associated.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/virología , Codón/genética , Uso de Codones , Biología Computacional/métodos , Coronavirus/genética , Infecciones por Coronavirus/metabolismo , Genes Virales , Genoma Viral , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Filogenia , Virus del SRAS/genética , SARS-CoV-2/genética
12.
Ann Lab Med ; 41(2): 129-138, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33063674

RESUMEN

Since its first report in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly emerged as a pandemic affecting nearly all countries worldwide. As the COVID-19 pandemic progresses, the need to identify genetic risk factors for susceptibility to this serious illness has emerged. Host genetic factors, along with other risk factors may help determine susceptibility to respiratory tract infections. It is hypothesized that the ACE2 gene, encoding angiotensin-converting enzyme 2 (ACE2), is a genetic risk factor for SARS-CoV-2 infection and is required by the virus to enter cells. Together with ACE2, transmembrane protease serine 2 (TMPRSS2) and dipeptidyl peptidase-4 (DPP4) also play an important role in disease severity. Evaluating the role of genetic variants in determining the direction of respiratory infections will help identify potential drug target candidates for further study in COVID-19 patients. We have summarized the latest reports demonstrating that ACE2 variants, their expression, and epigenetic factors may influence an individual's susceptibility to SARS-CoV-2 infection and disease outcome.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/patología , Variación Genética , Neumonía Viral/patología , Enzima Convertidora de Angiotensina 2 , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/virología , Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Susceptibilidad a Enfermedades , Expresión Génica , Humanos , Pandemias , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/virología , SARS-CoV-2 , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Índice de Severidad de la Enfermedad
13.
Ann Lab Med ; 41(2): 225-229, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33063685

RESUMEN

In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, an online laboratory surveillance system was established to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcription-PCR (rRT-PCR) testing capacities and results. SARS-CoV-2 rRT-PCR testing data were collected from 97 clinical laboratories, including 84 medical institutions and 13 independent clinical laboratories in Korea. We assessed the testing capacities to utilize SARS-CoV-2 rRT-PCR based on surveillance data obtained from February 7th to June 4th, 2020 and evaluated positive result characteristics according to the reagents used and sample types. A total of 1,890,319 SARS-CoV-2 rRT-PCR testing were performed, 2.3% of which were positive. Strong correlations were observed between the envelope (E) gene and RNA-dependent RNA polymerase (RdRp)/nucleocapsid (N) genes threshold cycle (Ct) values for each reagent. No statistically significant differences in gene Ct values were observed between the paired upper and lower respiratory tract samples, except in the N gene for nasopharyngeal swab and sputum samples. Our study showed that clinical laboratories in Korea have rapidly expanded their testing capacities in response to the COVID-19 outbreak, with a peak daily capacity of 34,193 tests. Rapid expansion in testing capacity is a critical component of the national response to the ongoing pandemic.


Asunto(s)
Betacoronavirus/genética , Servicios de Laboratorio Clínico/estadística & datos numéricos , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Betacoronavirus/aislamiento & purificación , COVID-19 , Proteínas de la Envoltura de Coronavirus , Infecciones por Coronavirus/virología , Humanos , Laboratorios de Hospital , Pandemias , Neumonía Viral/virología , ARN Viral/genética , ARN Viral/metabolismo , ARN Polimerasa Dependiente del ARN/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , República de Corea , SARS-CoV-2 , Proteínas del Envoltorio Viral/genética , Proteínas Virales/genética
15.
REVISA (Online) ; 10(1): 205-219, 2021.
Artículo en Portugués | LILACS | ID: biblio-1178055

RESUMEN

Objetivo: Analisar as variantes do vírus SARS-COV-2 causadoras da COVID-19 no Brasil, identificadas até fevereiro de 2021. Método: Estudo exploratório, descritivo, comparativo e quantitativo. Os dados foram adquiridos no Ministério da Saúde (MS). Resultados: Foram identificadas as variantes "VOC B.1.1.7, VOC202012/01 ou 201/501Y.V1" do Reino Unido, a "VOC B.1.351 ou VOC202012/02 ou 20H/501Y.V2" da África do Sul e a "VOC B.1.1.28.1 ou P.1 ou 20J/501Y.V3" do Brasil/Japão. As variantes VOV P.1 e a VOC B.1.1.7 foram as mais preponderantes do Brasil, com o universo de 334 casos, onde a primeira registrou 89,5% (n=299) e a segunda 10,5% (n=35). A região Nordeste (NE) registrou a maior preponderância das duas variantes contabilizando 32,6% (n=109) e o estado da Paraíba (PB) a maior preponderância da variante VOV P.1 com 23,1% (n=69). Considerações finais: As mutações do vírus SARS-CoV-2, causador da COVID-19, podem ter causado o surgimento de nova linhagem do vírus em circulação no Brasil.


To analyze the variants of the SARS-COV-2 virus that causes COVID-19 in Brazil, identified until february 2021. Method: Exploratory, descriptive, comparative and quantitative study. The data were acquired at the Ministry of Health (MS). Results: The variants "VOC B.1.1.7, VOC202012/01 or 201/501Y.V1" from the United Kingdom, "VOC B.1.351 or VOC202012/02 or 20H/501Y.V2" from South Africa and the "VOC B.1.1.28.1 or P.1 or 20J/501Y.V3" from Brazil/Japan. The VOV P.1 and VOC B.1.1.7 variants were the most prevalent in Brazil, with a universe of 334 cases, where the first registered 89.5% (n=299) and the second 10.5% (n=35). The Northeast region (NE) registered the highest preponderance of the two variants accounting for 32.6% (n=109) and the state of Paraíba (PB) the highest preponderance of the VOV P.1 variant with 23.1% (n=69) . Final considerations: Mutations of the SARS-CoV-2 virus, which causes COVID-19, may have caused the emergence of a new strain of the virus in circulation in Brazil.


Objetivo: Analizar las variantes del virus SARS-COV-2 que causa COVID-19 en Brasil, identificadas hasta febrero de 2021. Método: Estudio exploratorio, descriptivo, comparativo y cuantitativo. Los datos se obtuvieron del Ministerio de Salud (MS). Resultados: las variantes "VOC B.1.1.7, VOC202012/01 o 201/501Y.V1" del Reino Unido, "VOC B.1.351 o VOC202012/02 o 20H/501Y.V2" de Sudáfrica y el "VOC B.1.1.28.1 o P.1 o 20J/501Y.V3" de Brasil/Japón. Las variantes VOV P.1 y VOC B.1.1.7 fueron las más prevalentes en Brasil, con un universo de 334 casos, donde la primera registró 89,5% (n=299) y la segunda 10,5% (n=35). La región Nordeste (NE) registró la mayor preponderancia de las dos variantes con 32,6% (n=109) y el estado de Paraíba (PB) la mayor preponderancia de la variante VOV P.1 con 23,1% (n=69). Consideraciones finales: Las mutaciones del virus SARS-CoV-2, que causa COVID-19, pueden haber causado la aparición de una nueva cepa del virus en circulación en Brasil.


Asunto(s)
Humanos , Infecciones por Coronavirus/virología , Betacoronavirus/genética , Brasil/epidemiología , Infecciones por Coronavirus/epidemiología
16.
PLoS Genet ; 16(12): e1009272, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33332358

RESUMEN

The Betacoronaviruses comprise multiple subgenera whose members have been implicated in human disease. As with SARS, MERS and now SARS-CoV-2, the origin and emergence of new variants are often attributed to events of recombination that alter host tropism or disease severity. In most cases, recombination has been detected by searches for excessively similar genomic regions in divergent strains; however, such analyses are complicated by the high mutation rates of RNA viruses, which can produce sequence similarities in distant strains by convergent mutations. By applying a genome-wide approach that examines the source of individual polymorphisms and that can be tested against null models in which recombination is absent and homoplasies can arise only by convergent mutations, we examine the extent and limits of recombination in Betacoronaviruses. We find that recombination accounts for nearly 40% of the polymorphisms circulating in populations and that gene exchange occurs almost exclusively among strains belonging to the same subgenus. Although experimental studies have shown that recombinational exchanges occur at random along the coronaviral genome, in nature, they are vastly overrepresented in regions controlling viral interaction with host cells.


Asunto(s)
Betacoronavirus/clasificación , Betacoronavirus/genética , Recombinación Genética/genética , Glicoproteína de la Espiga del Coronavirus/genética , Intercambio Genético/genética , Genes Virales/genética , Genoma Viral/genética , Especificidad del Huésped/genética , Modelos Genéticos , Polimorfismo Genético , SARS-CoV-2/clasificación , SARS-CoV-2/genética , Tropismo Viral/genética
18.
Rev. esp. quimioter ; 33(6): 410-414, dic. 2020. tab
Artículo en Español | IBECS | ID: ibc-195991

RESUMEN

INTRODUCCIÓN: El diagnóstico de la infección por SARSCoV-2 presenta limitaciones. La RT-PCR en frotis nasofaríngeo es la prueba considerada como el patrón oro, aunque puede ofrecer falsos negativos. El objetivo de este trabajo ha sido evaluar la utilidad de repetir el frotis nasofaríngeo en pacientes con resultado negativo en función de las diferentes probabilidades clínicas. MÉTODOS: Estudio observacional retrospectivo de los primeros pacientes ingresados en el Hospital Universitario Marqués de Valdecilla en dos plantas COVID de Medicina Interna durante marzo-abril del 2020. La RT-PCR para la detección de al menos dos dianas de los principales genes (E, N, RdRP, ORFab1) y el test de detección de anticuerpos para la detección de al menos IgG. RESULTADOS: Se analizaron 145 pacientes hospitalizados; 98 (67,5%) con el diagnóstico de SARS-CoV-2. Las variables predictivas independientes de SARS-CoV-2 fueron: contacto epidemiológico con otro paciente COVID-19, presentación clínica como neumonía, ausencia de neumonía en el año previo, inicio de síntomas >7 días al ingreso, ≥2 síntomas -tos, disnea y fiebre- y lactato deshidrogenasa >350 U/L (p < 0,05). Un score basado en estas variables presentó un área bajo la curva ROC (ABC ROC) de 0,89 (IC95 0,831-0,946; p < 0,001). El rendimiento de la RT-PCR en su primera determinación fue del 54,9%. La repetición de la prueba permitió detectar un 16% de casos adicionales. El rendimiento global de sucesivas RT-PCR en pacientes con baja probabilidad clínica fue inferior al 5%. CONCLUSIÓN: Hemos definido un score de probabilidad pre-prueba basado en datos epidemiológicos y clínicos con una buena precisión para el diagnóstico por infección SARSCoV-2. La repetición del frotis nasofaríngeo puede evitar errores de muestreo sólo en escenarios de intermedia-alta probabilidad clínica pre-prueba


BACKGROUND: The diagnosis of SARS-CoV-2 infection presents some limitations. RT-PCR in nasopharyngeal swabs is considered the gold standard for the diagnosis, although it can have false negative results. We aimed to analyze the accuracy of repeating nasopharyngeal swabs based on different clinical probabilities. METHODS: Retrospective observational study of the first patients admitted to a two COVID Internal Medicine wards at the University Hospital Marqués de Valdecilla, Santander, from March to April 2020. RT-PCR targering E, N, RdRP and ORFab1 genes and antibody tests detecting IgG. RESULTS: A total of 145 hospitalized patients with suspected SARS-Cov2 infection were admitted and in 98 (67.5%) diagnosis was confirmed. The independent predictive variables for SARS-CoV-2 infection were: epidemiological contact, clinical presentation as pneumonia, absence of pneumonia in the last year, onset of symptoms > 7 days, two or more of the following symptoms -dyspnea, cough or fever- and serum lactate dehydrogenase levels >350 U/L (p < 0.05). A score based on these variables yielded an AUC-ROC of 0.89 (CI95%, 0.831-0.946; p < 0.001). The accuracy of the first nasopharyngeal swabs was 54.9%. Repeating nasopharyngeal swabs two or three times allows to detect an additional 16% of positive cases. The overall accuracy of successive RT-PCR tests in patients with low pre-test probability was <5%. CONCLUSIONS: We have defined a pre-test probability score based on epidemiological and clinical data with a high accuracy for diagnosis of SARS-CoV-2. Repeating nasopharyngeal swabs avoids sampling errors, but only in medium of high probability pre-test clinical scenarios


Asunto(s)
Humanos , Masculino , Femenino , Anciano , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Betacoronavirus/aislamiento & purificación , Pandemias , Anticuerpos Antivirales/análisis , Área Bajo la Curva , Distribución de Chi-Cuadrado , Genes Virales , Nasofaringe/virología , Probabilidad , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Betacoronavirus/genética , Betacoronavirus/inmunología
20.
Trials ; 21(1): 939, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33225960

RESUMEN

BACKGROUND: Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNß-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNß anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNß was indicated as the key component of a successful therapeutic combination. METHODS: This is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). One hundred twenty-six patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 2:1 to IFNß-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNß-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 h apart, for a total of 2 weeks. The primary outcome is the time to negative conversion of SARS-CoV-2 nasopharyngeal swabs. Secondary outcomes include improvement or worsening in a clinical severity score measured on a 7-point ordinal scale (including transfer to intensive care unit and death), oxygen- and ventilator-free days, mortality, changes in pulmonary computed tomography severity score, hospital stay duration, reduction of viral load measured on nasopharyngeal swabs, number of serious adverse events, and changes in biochemical markers of organ dysfunction. Exploratory outcomes include blood cell counts, cytokine and inflammatory profile, peripheral mRNA expression profiles of interferon-stimulated genes, and antibodies to SARS-CoV-2 and to IFNß-1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFNß-1a in COVID-19 patients. DISCUSSION: Potential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFNß-1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFNß-1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment. TRIAL REGISTRATION: EudraCT 2020-002458-25. Registered on May 11, 2020 ClinicalTrials.gov Identifier: NCT04449380.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Interferón beta-1a/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adulto , Antivirales/administración & dosificación , Betacoronavirus/genética , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Manejo de Datos , Femenino , Humanos , Inyecciones Subcutáneas , Interferón beta-1a/administración & dosificación , Italia/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Mortalidad/tendencias , Oxígeno/administración & dosificación , Oxígeno/uso terapéutico , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/virología , Resultado del Tratamiento , Carga Viral/efectos de los fármacos
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