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1.
Front Immunol ; 11: 2063, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-868947

RESUMEN

Background: Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. Neutrophil infiltration was also noted on the pathological findings from autopsies. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19. Methods: A retrospective analysis was performed on 55 COVID-19 patients classified as mild (n = 22), moderate (n = 25), and severe (n = 8) according to the Guidelines released by the National Health Commission of China. Trends relating leukocyte counts and lungs examined by chest CT scan were quantified by Bayesian inference. Transcriptional signatures of host immune cells of four COVID19 patients were analyzed by RNA sequencing of lung specimens and BALF. Results: Neutrophilia occurred in 6 of 8 severe patients at 7-19 days after symptom onset, coinciding with lesion progression. Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3-1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein-protein interaction network analysis. Conclusion: Excessive neutrophils and associated NETs could explain the pathogenesis of lung injury in COVID-19 pneumonia.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/inmunología , Trampas Extracelulares/genética , Activación Neutrófila/genética , Neutrófilos/inmunología , Neumonía Viral/inmunología , Adulto , Anciano , Teorema de Bayes , Infecciones por Coronavirus/virología , Femenino , Humanos , Recuento de Leucocitos , Lesión Pulmonar/inmunología , Lesión Pulmonar/patología , Masculino , Persona de Mediana Edad , Infiltración Neutrófila/inmunología , Pandemias , Neumonía Viral/virología , Mapas de Interacción de Proteínas/inmunología , ARN Viral/genética , Estudios Retrospectivos , Transcriptoma
2.
Front Immunol ; 11: 1836, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-868937

RESUMEN

Examining CD8+ and CD4+ T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8+ and 50 CD4+ T cell epitopes, many inducing strong and prevalent (i.e., immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4+ T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4+ T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4+ T cell responses. Our T cell epitope discovery approach uses a combination of (1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4+ and/or CD8+ T cell epitopes, (2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, (3) generation of peptide-HLA tetramers to identify T cell epitopes, and (4) analysis of ex vivo T cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4+ and CD8+ T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g., SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/inmunología , Vacunación , Vacuna contra la Fiebre Amarilla/inmunología , Fiebre Amarilla/prevención & control , Virus de la Fiebre Amarilla/inmunología , Betacoronavirus/inmunología , Estudios de Cohortes , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Voluntarios Sanos , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Inmunogenicidad Vacunal , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/virología , Fiebre Amarilla/virología
3.
JMIR Public Health Surveill ; 6(3): e18965, 2020 09 18.
Artículo en Inglés | MEDLINE | ID: covidwho-862937

RESUMEN

BACKGROUND: Throughout March 2020, leaders in countries across the world were making crucial decisions about how and when to implement public health interventions to combat the coronavirus disease (COVID-19). They urgently needed tools to help them to explore what will work best in their specific circumstances of epidemic size and spread, and feasible intervention scenarios. OBJECTIVE: We sought to rapidly develop a flexible, freely available simulation model for use by modelers and researchers to allow investigation of how various public health interventions implemented at various time points might change the shape of the COVID-19 epidemic curve. METHODS: "COVOID" (COVID-19 Open-Source Infection Dynamics) is a stochastic individual contact model (ICM), which extends the ICMs provided by the open-source EpiModel package for the R statistical computing environment. To demonstrate its use and inform urgent decisions on March 30, 2020, we modeled similar intervention scenarios to those reported by other investigators using various model types, as well as novel scenarios. The scenarios involved isolation of cases, moderate social distancing, and stricter population "lockdowns" enacted over varying time periods in a hypothetical population of 100,000 people. On April 30, 2020, we simulated the epidemic curve for the three contiguous local areas (population 287,344) in eastern Sydney, Australia that recorded 5.3% of Australian cases of COVID-19 through to April 30, 2020, under five different intervention scenarios and compared the modeled predictions with the observed epidemic curve for these areas. RESULTS: COVOID allocates each member of a population to one of seven compartments. The number of times individuals in the various compartments interact with each other and their probability of transmitting infection at each interaction can be varied to simulate the effects of interventions. Using COVOID on March 30, 2020, we were able to replicate the epidemic response patterns to specific social distancing intervention scenarios reported by others. The simulated curve for three local areas of Sydney from March 1 to April 30, 2020, was similar to the observed epidemic curve in terms of peak numbers of cases, total numbers of cases, and duration under a scenario representing the public health measures that were actually enacted, including case isolation and ramp-up of testing and social distancing measures. CONCLUSIONS: COVOID allows rapid modeling of many potential intervention scenarios, can be tailored to diverse settings, and requires only standard computing infrastructure. It replicates the epidemic curves produced by other models that require highly detailed population-level data, and its predicted epidemic curve, using parameters simulating the public health measures that were enacted, was similar in form to that actually observed in Sydney, Australia. Our team and collaborators are currently developing an extended open-source COVOID package comprising of a suite of tools to explore intervention scenarios using several categories of models.


Asunto(s)
Trazado de Contacto , Infecciones por Coronavirus/prevención & control , Modelos Biológicos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Salud Pública , Aislamiento Social , Australia , Betacoronavirus , Coronavirus , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Epidemias , Humanos , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , Cuarentena
4.
J Med Internet Res ; 22(10): e22299, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: covidwho-862642

RESUMEN

BACKGROUND: COVID-19 became a global pandemic not long after its identification in late 2019. The genomes of SARS-CoV-2 are being rapidly sequenced and shared on public repositories. To keep up with these updates, scientists need to frequently refresh and reclean data sets, which is an ad hoc and labor-intensive process. Further, scientists with limited bioinformatics or programming knowledge may find it difficult to analyze SARS-CoV-2 genomes. OBJECTIVE: To address these challenges, we developed CoV-Seq, an integrated web server that enables simple and rapid analysis of SARS-CoV-2 genomes. METHODS: CoV-Seq is implemented in Python and JavaScript. The web server and source code URLs are provided in this article. RESULTS: Given a new sequence, CoV-Seq automatically predicts gene boundaries and identifies genetic variants, which are displayed in an interactive genome visualizer and are downloadable for further analysis. A command-line interface is available for high-throughput processing. In addition, we aggregated all publicly available SARS-CoV-2 sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID), National Center for Biotechnology Information (NCBI), European Nucleotide Archive (ENA), and China National GeneBank (CNGB), and extracted genetic variants from these sequences for download and downstream analysis. The CoV-Seq database is updated weekly. CONCLUSIONS: We have developed CoV-Seq, an integrated web service for fast and easy analysis of custom SARS-CoV-2 sequences. The web server provides an interactive module for the analysis of custom sequences and a weekly updated database of genetic variants of all publicly accessible SARS-CoV-2 sequences. We believe CoV-Seq will help improve our understanding of the genetic underpinnings of COVID-19.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/virología , Visualización de Datos , Bases de Datos Genéticas , Genoma Viral/genética , Neumonía Viral/virología , Programas Informáticos , Biología Computacional , Infecciones por Coronavirus/epidemiología , Humanos , Pandemias , Neumonía Viral/epidemiología
5.
Am J Phys Med Rehabil ; 99(10): 873-875, 2020 10.
Artículo en Inglés | MEDLINE | ID: covidwho-860315

RESUMEN

A 65-yr-old man visited a primary care hospital with a continued fever of 38°C for 3 days. As his fever did not improve until 8 days after, he was admitted into another acute care hospital, where his respiratory condition rapidly worsened. Therefore, the patient was transferred to our hospital. On the day of transfer (day 1), he was started on mechanical ventilation. COVID-19 was diagnosed using a polymerase chain reaction assay 6 days after admission (day 6). The rehabilitation therapy was begun on day 6. The initial rehabilitation programs focused on positioning and postural drainage. The patient was extubated on day 19, and he began standing and stepping on the same day. Gait exercises began on day 22, and endurance training was initiated on day 28. The patient was discharged from our hospital on day 34 as he met the physical function milestones. One month after discharge, the Medical Research Council sum score and Barthel Index had each improved; therefore, muscle strength and daily activities had returned to normal. It was assumed that mobilization should be performed as soon as possible after the end of sedation during the acute phase of severe COVID-19 infection in patients receiving mechanical ventilation.


Asunto(s)
Infecciones por Coronavirus/rehabilitación , Drenaje Postural/métodos , Terapia por Ejercicio/métodos , Neumonía Viral/rehabilitación , Terapia Respiratoria/métodos , Anciano , Betacoronavirus , Infecciones por Coronavirus/virología , Humanos , Japón , Masculino , Pandemias , Neumonía Viral/virología , Respiración Artificial , Resultado del Tratamiento
6.
Am J Phys Med Rehabil ; 99(10): 870-872, 2020 10.
Artículo en Inglés | MEDLINE | ID: covidwho-860314

RESUMEN

The coronavirus 2019 pandemic has resulted in a surge of patients with acute respiratory distress syndrome. Prone positioning may be used in such patients to optimize oxygenation. Severe infections may leave survivors with significant functional impairment necessitating rehabilitation. Those who have experienced prolonged prone positioning are at increased risk for complications not typically associated with critical illness. This case report describes the course and clinical findings of a survivor of acute respiratory distress syndrome due to coronavirus 2019 who was prone positioned while in intensive care and subsequently admitted to an inpatient rehabilitation facility. Her related complications, as well as those described in the literature, are reviewed. Critical elements of a comprehensive rehabilitation treatment plan for those who have been prone positioned, including implementation of preventive strategies, as well as early recognition and treatment of related injuries, will be described.


Asunto(s)
Infecciones por Coronavirus/fisiopatología , Cuidados Críticos/métodos , Posicionamiento del Paciente/efectos adversos , Neumonía Viral/fisiopatología , Posición Prona , Terapia Respiratoria/métodos , Adulto , Betacoronavirus , Infecciones por Coronavirus/rehabilitación , Infecciones por Coronavirus/virología , Femenino , Humanos , Pandemias , Neumonía Viral/rehabilitación , Neumonía Viral/virología
7.
Am J Phys Med Rehabil ; 99(10): 865-869, 2020 10.
Artículo en Inglés | MEDLINE | ID: covidwho-860313

RESUMEN

The COVID-19 pandemic affects a large number of patients with a rapid progression of respiratory failure often requiring hospitalization or intensive care unit treatment in some patients. Survivors of severe COVID-19 experience persistent weakness and cardiorespiratory failure. Feasibility and potential benefit of cardiopulmonary rehabilitation after COVID-19 remains unclear. Therefore, we retrospectively analyzed a cohort of COVID-19 patients in a single-center inpatient rehabilitation clinic and describe performance and outcome during cardiopulmonary rehabilitation.Patients were referred from acute care hospitals for rehabilitation after severe COVID-19. The cohort (N = 28) was divided in ventilated or not ventilated patients for further analysis. Fifty percent were female, the mean age was 66 yrs, and patients stayed in the acute hospital for 19.3 ± 10.7 days before referral for cardiopulmonary rehabilitation. Seventeen patients (61%) needed previous intensive care unit treatment in the acute care hospital. Risk factors, assessments, and questionnaires on admission were comparable in both groups. Significant enhancements were observed in 6-min walking test and feeling thermometer, which were independent of previous ventilation status.In conclusion, comprehensive cardiopulmonary rehabilitation after COVID-19 is safe, feasible, and effective. Improvements in physical performance and subjective health status were independent of previous ventilation.


Asunto(s)
Betacoronavirus , Rehabilitación Cardiaca/métodos , Infecciones por Coronavirus/rehabilitación , Neumonía Viral/rehabilitación , Terapia Respiratoria/métodos , Anciano , Infecciones por Coronavirus/virología , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/virología , Estudios Retrospectivos , Resultado del Tratamiento
8.
Rev Med Virol ; 30(5): e2140, 2020 09.
Artículo en Inglés | MEDLINE | ID: covidwho-848179

RESUMEN

A knowledge-based cybernetic framework model representing the dynamics of SARS-CoV-2 inside the human body has been studied analytically and in silico to explore the pathophysiologic regulations. The following modeling methodology was developed as a platform to introduce a predictive tool supporting a therapeutic approach to Covid-19 disease. A time-dependent nonlinear system of ordinary differential equations model was constructed involving type-I cells, type-II cells, SARS-CoV-2 virus, inflammatory mediators, interleukins along with host pulmonary gas exchange rate, thermostat control, and mean pressure difference. This formalism introduced about 17 unknown parameters. Estimating these unknown parameters requires a mathematical association with the in vivo sparse data and the dynamic sensitivities of the model. The cybernetic model can simulate a dynamic response to the reduced pulmonary alveolar gas exchange rate, thermostat control, and mean pressure difference under a very critical condition based on equilibrium (steady state) values of the inflammatory mediators and system parameters. In silico analysis of the current cybernetical approach with system dynamical modeling can provide an intellectual framework to help experimentalists identify more active therapeutic approaches.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/inmunología , Interacciones Huésped-Patógeno/inmunología , Pulmón/inmunología , Dinámicas no Lineales , Neumonía Viral/inmunología , Proteínas de Fase Aguda/antagonistas & inhibidores , Proteínas de Fase Aguda/genética , Proteínas de Fase Aguda/inmunología , Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Betacoronavirus/crecimiento & desarrollo , Temperatura Corporal , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Citocinas/antagonistas & inhibidores , Citocinas/genética , Citocinas/inmunología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/virología , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/genética , Humanos , Pulmón/efectos de los fármacos , Pulmón/virología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/virología , Pandemias , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/inmunología , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/patología , Neumonía Viral/virología , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Intercambio Gaseoso Pulmonar/inmunología , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología
10.
Euro Surveill ; 25(27)2020 07.
Artículo en Inglés | MEDLINE | ID: covidwho-845124

RESUMEN

Laboratory preparedness with quality-assured diagnostic assays is essential for controlling the current coronavirus disease (COVID-19) outbreak. We conducted an external quality assessment study with inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples to support clinical laboratories with a proficiency testing option for molecular assays. To analyse SARS-CoV-2 testing performance, we used an online questionnaire developed for the European Union project RECOVER to assess molecular testing capacities in clinical diagnostic laboratories.


Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Técnicas de Laboratorio Clínico/normas , Infecciones por Coronavirus/diagnóstico , Coronavirus/aislamiento & purificación , Técnicas de Diagnóstico Molecular/métodos , Pandemias , Neumonía Viral/diagnóstico , Betacoronavirus , Servicios de Laboratorio Clínico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Brotes de Enfermedades , Europa (Continente) , Humanos , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/virología , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , Sensibilidad y Especificidad , Encuestas y Cuestionarios
11.
JCO Glob Oncol ; 6: 1428-1438, 2020 09.
Artículo en Inglés | MEDLINE | ID: covidwho-844422

RESUMEN

PURPOSE: The COVID-19 pandemic affected health care systems globally and resulted in the interruption of usual care in many health care facilities, exposing vulnerable patients with cancer to significant risks. Our study aimed to evaluate the impact of this pandemic on cancer care worldwide. METHODS: We conducted a cross-sectional study using a validated web-based questionnaire of 51 items. The questionnaire obtained information on the capacity and services offered at these centers, magnitude of disruption of care, reasons for disruption, challenges faced, interventions implemented, and the estimation of patient harm during the pandemic. RESULTS: A total of 356 centers from 54 countries across six continents participated between April 21 and May 8, 2020. These centers serve 716,979 new patients with cancer a year. Most of them (88.2%) reported facing challenges in delivering care during the pandemic. Although 55.34% reduced services as part of a preemptive strategy, other common reasons included an overwhelmed system (19.94%), lack of personal protective equipment (19.10%), staff shortage (17.98%), and restricted access to medications (9.83%). Missing at least one cycle of therapy by > 10% of patients was reported in 46.31% of the centers. Participants reported patient exposure to harm from interruption of cancer-specific care (36.52%) and noncancer-related care (39.04%), with some centers estimating that up to 80% of their patients were exposed to harm. CONCLUSION: The detrimental impact of the COVID-19 pandemic on cancer care is widespread, with varying magnitude among centers worldwide. Additional research to assess this impact at the patient level is required.


Asunto(s)
Instituciones Oncológicas/estadística & datos numéricos , Infecciones por Coronavirus/prevención & control , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Oncología Médica/estadística & datos numéricos , Neoplasias/terapia , Pandemias/prevención & control , Neumonía Viral/prevención & control , Betacoronavirus/patogenicidad , Instituciones Oncológicas/normas , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Estudios Transversales , Carga Global de Enfermedades , Accesibilidad a los Servicios de Salud/normas , Humanos , Control de Infecciones/normas , Cooperación Internacional , Oncología Médica/normas , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , Encuestas y Cuestionarios/estadística & datos numéricos
12.
BMC Infect Dis ; 20(1): 745, 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: covidwho-843296

RESUMEN

BACKGROUND: Workers and residents in Care Homes are considered at special risk for the acquisition of SARS-CoV-2 infection, due to the infectivity and high mortality rate in the case of residents, compared to other containment areas. The role of presymptomatic people in transmission has been shown to be important and the early detection of these people is critical for the control of new outbreaks. Pooling strategies have proven to preserve SARS-CoV-2 testing resources. The aims of the present study, based in our local experience, were (a) to describe SARS-CoV-2 prevalence in institutionalized people in Galicia (Spain) during the Coronavirus pandemic and (b) to evaluate the expected performance of a pooling strategy using RT-PCR for the next rounds of screening of institutionalized people. METHODS: A total of 25,386 Nasopharyngeal swab samples from the total of the residents and workers at Care Homes in Galicia (March to May 2020) were individually tested using RT-PCR. Prevalence and quantification cycle (Cq) value distribution of positives was calculated. Besides, 26 pools of 20 samples and 14 pools of 5 samples were tested using RT-PCR as well (1 positive/pool). Pooling proof of concept was performed in two populations with 1.7 and 2% prevalence. RESULTS: Distribution of SARS-CoV-2 infection at Care Homes was uneven (0-60%). As the virus circulation global rate was low in our area (3.32%), the number of people at risk of acquiring the infection continues to be very high. In this work, we have successfully demonstrated that pooling of different groups of samples at low prevalence clusters, can be done with a small average delay on Cq values (5 and 2.85 cycles for pools of 20 and 5 samples, respectively). CONCLUSIONS: A new screening system with guaranteed protection is required for small clusters, previously covered with individual testing. Our proposal for Care Homes, once prevalence zero is achieved, would include successive rounds of testing using a pooling solution for transmission control preserving testing resources. Scale-up of this method may be of utility to confront larger clusters to avoid the viral circulation and keeping them operative.


Asunto(s)
Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/prevención & control , Casas de Salud/estadística & datos numéricos , Pandemias/prevención & control , Neumonía Viral/diagnóstico , Neumonía Viral/prevención & control , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Brotes de Enfermedades/prevención & control , Brotes de Enfermedades/estadística & datos numéricos , Humanos , Neumonía Viral/transmisión , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , España/epidemiología
13.
PLoS One ; 15(8): e0237300, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-842269

RESUMEN

The outbreak of COVID-19 across the world has posed unprecedented and global challenges on multiple fronts. Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases and main protease for viral replication. Using the bioinformatics and structural modelling approach, we modelled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS- CoV-1, and is highly conserved in the N-terminus regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modelling, we found that the most favorable structure could function as a gated ion channel conducting H+ ions. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds which was further validated by insertion of the E protein in an ERGIC-mimic membrane. Additionally, two distinct "core" structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel. We propose this as a mechanism of viral ion channeling activity which plays a critical role in viral infection and pathogenesis. In addition, it provides a structural basis and additional avenues for vaccine development and generating therapeutic interventions against the virus.


Asunto(s)
Betacoronavirus/química , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Proteínas del Envoltorio Viral/química , Proteínas del Envoltorio Viral/genética , Betacoronavirus/aislamiento & purificación , Simulación por Computador , Infecciones por Coronavirus/virología , Humanos , Hidrógeno , Enlace de Hidrógeno , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Neumonía Viral/virología , Mutación Puntual , Conformación Proteica , Homología Estructural de Proteína , Vacunas Atenuadas , Vacunas de Productos Inactivados , Proteínas del Envoltorio Viral/inmunología , Vacunas Virales , Agua/química
14.
PLoS One ; 15(8): e0237559, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-840723

RESUMEN

BACKGROUND: The world is going through the critical phase of COVID-19 pandemic, caused by human coronavirus, SARS-CoV-2. Worldwide concerted effort to identify viral genomic changes across different sub-types has identified several strong changes in the coding region. However, there have not been many studies focusing on the variations in the 5' and 3' untranslated regions and their consequences. Considering the possible importance of these regions in host mediated regulation of viral RNA genome, we wanted to explore the phenomenon. METHODS: To have an idea of the global changes in 5' and 3'-UTR sequences, we downloaded 8595 complete and high-coverage SARS-CoV-2 genome sequence information from human host in FASTA format from Global Initiative on Sharing All Influenza Data (GISAID) from 15 different geographical regions. Next, we aligned them using Clustal Omega software and investigated the UTR variants. We also looked at the putative host RNA binding protein (RBP) and microRNA binding sites in these regions by 'RBPmap' and 'RNA22 v2' respectively. Expression status of selected RBPs and microRNAs were checked in lungs tissue. RESULTS: We identified 28 unique variants in SARS-CoV-2 UTR region based on a minimum variant percentage cut-off of 0.5. Along with 241C>T change the important 5'-UTR change identified was 187A>G, while 29734G>C, 29742G>A/T and 29774C>T were the most familiar variants of 3'UTR among most of the continents. Furthermore, we found that despite the variations in the UTR regions, binding of host RBP to them remains mostly unaltered, which further influenced the functioning of specific miRNAs. CONCLUSION: Our results, shows for the first time in SARS-Cov-2 infection, a possible cross-talk between host RBPs-miRNAs and viral UTR variants, which ultimately could explain the mechanism of escaping host RNA decay machinery by the virus. The knowledge might be helpful in developing anti-viral compounds in future.


Asunto(s)
Regiones no Traducidas 3'/genética , Regiones no Traducidas 5'/genética , Betacoronavirus/genética , Infecciones por Coronavirus/metabolismo , Genoma Viral/genética , Inestabilidad Genómica/genética , Interacciones Huésped-Patógeno/genética , MicroARNs/metabolismo , Neumonía Viral/metabolismo , ARN Viral/metabolismo , Proteínas de Unión al ARN/metabolismo , Secuencia de Bases , Sitios de Unión , Infecciones por Coronavirus/virología , Humanos , Sistemas de Lectura Abierta/genética , Pandemias , Neumonía Viral/virología , Unión Proteica/genética
15.
Cancer Cytopathol ; 128(10): 679-680, 2020 10.
Artículo en Inglés | MEDLINE | ID: covidwho-840101
19.
Emerg Infect Dis ; 26(10): 2497-2499, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: covidwho-836160

RESUMEN

Along with positive SARS-CoV-2 RNA in nasopharyngeal swabs, viral RNA was detectable at high concentration for >3 weeks in fecal samples from 12 mildly symptomatic and asymptomatic children with COVID-19 in Seoul, South Korea. Saliva also tested positive during the early phase of infection. If proven infectious, feces and saliva could serve as transmission sources.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Heces/virología , Nasofaringe/virología , Neumonía Viral/virología , ARN Viral/análisis , Saliva/virología , Adolescente , Infecciones Asintomáticas , Niño , Preescolar , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/orina , Humanos , Lactante , Recién Nacido , Pandemias , Plasma/virología , Neumonía Viral/transmisión , Neumonía Viral/orina , República de Corea , Orina/virología , Carga Viral
20.
BMC Infect Dis ; 20(1): 735, 2020 Oct 07.
Artículo en Inglés | MEDLINE | ID: covidwho-835820

RESUMEN

BACKGROUND: The pandemic of COVID-19 has occurred close on the heels of a global resurgence of measles. In 2019, an unprecedented epidemic of measles affected Samoa, requiring a state of emergency to be declared. Measles causes an immune amnesia which can persist for over 2 years after acute infection and increases the risk of a range of other infections. METHODS: We modelled the potential impact of measles-induced immune amnesia on a COVID-19 epidemic in Samoa using data on measles incidence in 2018-2019, population data and a hypothetical COVID-19 epidemic. RESULTS: The young population structure and contact matrix in Samoa results in the most transmission occurring in young people < 20 years old. The highest rate of death is the 60+ years old, but a smaller peak in death may occur in younger people, with more than 15% of total deaths in the age group under 20 years old. Measles induced immune amnesia could increase the total number of cases by 8% and deaths by more than 2%. CONCLUSIONS: Samoa, which had large measles epidemics in 2019-2020 should focus on rapidly achieving high rates of measles vaccination and enhanced surveillance for COVID-19, as the impact may be more severe due to measles-induced immune paresis. This applies to other severely measles-affected countries in the Pacific, Europe and elsewhere.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/mortalidad , Sarampión/epidemiología , Sarampión/mortalidad , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Preescolar , Comorbilidad , Infecciones por Coronavirus/virología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Sarampión/inmunología , Sarampión/prevención & control , Persona de Mediana Edad , Modelos Estadísticos , Pandemias , Neumonía Viral/virología , Samoa/epidemiología , Vacunación , Adulto Joven
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