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1.
Biochem Biophys Res Commun ; 529(2): 251-256, 2020 08 20.
Article in English | MEDLINE | ID: covidwho-692859

ABSTRACT

The nucleocapsid protein is significant in the formation of viral RNA of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accounting for the largest proportion of viral structural proteins. Here, we report for the first time that the 11S proteasomal activator PA28γ regulates the intracellular abundance of the SARS-CoV-2 N protein (nCoV N). Furthermore, we have identified proteasome activator PA28γ as a nCoV N binding protein by co-immunoprecipitation assay. As a result of their interaction, nCoV N could be degraded by PA28γ-20S in vitro degradation assay. This was also demonstrated by blocking de novo protein synthesis with cycloheximide. The stability of nCoV N in PA28γ-knockout cells was greater than in PA28γ-wildtype cells. Notably, immunofluorescence staining revealed that knockout of the PA28γ gene in cells led to the transport of nCoV N from the nucleus to the cytoplasm. Overexpression of PA28γ enhanced proteolysis of nCoV N compared to that in PA28γ-N151Y cells containing a dominant-negative PA28γ mutation, which reduced this process. These results suggest that PA28γ binding is important in regulating 20S proteasome activity, which in turn regulates levels of the critical nCoV N nucleocapsid protein of SARS-CoV-2, furthering our understanding of the pathogenesis of COVID-19.


Subject(s)
Autoantigens/metabolism , Betacoronavirus/metabolism , Coronavirus Infections/metabolism , Nucleocapsid Proteins/metabolism , Pneumonia, Viral/metabolism , Proteasome Endopeptidase Complex/metabolism , Proteolysis , Coronavirus Infections/virology , HEK293 Cells , Humans , In Vitro Techniques , Pandemics , Pneumonia, Viral/virology , Protein Binding , Protein Stability , Protein Transport
2.
Gac Med Mex ; 156(3): 246-248, 2020.
Article in English | MEDLINE | ID: covidwho-692409

ABSTRACT

Except for pregnant women, the management of critically ill patients with COVID-19 during the pandemic includes the standard procedures that are used for any patient that requires to be attended to at the intensive care unit, as well as limited administration of crystalloid solutions, orotracheal intubation, invasive mechanical ventilation in the event of patient clinical deterioration, and muscle relaxants continuous infusion only if necessary. Non-invasive mechanical ventilation and high-flow oxygen therapy are not recommended due to the generation of aerosol (associated with risk of viral spread among health personnel), and neither is extracorporeal membrane oxygenation or the use of steroids. So far, there is no specific antiviral treatment for patients with COVID-19, and neither are there results of controlled trials supporting the use of any.


Subject(s)
Coronavirus Infections/therapy , Critical Care/methods , Intensive Care Units , Pneumonia, Viral/therapy , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Critical Illness , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pandemics , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission
3.
Int J Mol Sci ; 21(12)2020 Jun 26.
Article in English | MEDLINE | ID: covidwho-692289

ABSTRACT

In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of coronaviruses in the aftermath of the 2002-2003 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-2020 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2. We focus on shared genomic features of the betacoronaviruses and the application of genomic information to phylogenetic analysis, molecular epidemiology and the design of diagnostic systems, potential drugs and vaccine candidates.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Genome, Viral , Pandemics/prevention & control , Pneumonia, Viral/virology , Animals , Betacoronavirus/immunology , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Drug Design , Genes, Viral , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , Molecular Epidemiology , Phylogeny , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , SARS Virus/genetics , Severe Acute Respiratory Syndrome/virology , Viral Vaccines/genetics , Viral Vaccines/immunology
9.
J Virol ; 94(15)2020 07 16.
Article in English | MEDLINE | ID: covidwho-690841

ABSTRACT

Currently, there are four seasonal coronaviruses associated with relatively mild respiratory tract disease in humans. However, there is also a plethora of animal coronaviruses which have the potential to cross the species border. This regularly results in the emergence of new viruses in humans. In 2002, severe acute respiratory syndrome coronavirus (SARS-CoV) emerged and rapidly disappeared in May 2003. In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a possible threat to humans, but its pandemic potential so far is minimal, as human-to-human transmission is ineffective. The end of 2019 brought us information about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergence, and the virus rapidly spread in 2020, causing an unprecedented pandemic. At present, studies on the virus are carried out using a surrogate system based on the immortalized simian Vero E6 cell line. This model is convenient for diagnostics, but it has serious limitations and does not allow for understanding of the biology and evolution of the virus. Here, we show that fully differentiated human airway epithelium cultures constitute an excellent model to study infection with the novel human coronavirus SARS-CoV-2. We observed efficient replication of the virus in the tissue, with maximal replication at 2 days postinfection. The virus replicated in ciliated cells and was released apically.IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged by the end of 2019 and rapidly spread in 2020. At present, it is of utmost importance to understand the biology of the virus, rapidly assess the treatment potential of existing drugs, and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on SARS-CoV-2.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Respiratory Mucosa/virology , Severe Acute Respiratory Syndrome/virology , Virus Replication , Animals , Cell Line , Cells, Cultured , Chlorocebus aethiops , Humans , Pandemics , Vero Cells
11.
JMIR Public Health Surveill ; 6(3): e21163, 2020 07 17.
Article in English | MEDLINE | ID: covidwho-690445

ABSTRACT

BACKGROUND: The coronavirus disease (COVID-19) pandemic has caused an unprecedented worldwide public health crisis that requires new management approaches. COVIDApp is a mobile app that was adapted for the management of institutionalized individuals in long-term care facilities. OBJECTIVE: The aim of this paper is to report the implementation of this innovative tool for the management of long-term care facility residents as a high-risk population, specifically for early identification and self-isolation of suspected cases, remote monitoring of mild cases, and real-time monitoring of the progression of the infection. METHODS: COVIDApp was implemented in 196 care centers in collaboration with 64 primary care teams. The following parameters of COVID-19 were reported daily: signs/symptoms; diagnosis by reverse transcriptase-polymerase chain reaction; absence of symptoms for ≥14 days; total deaths; and number of health care workers isolated with suspected COVID-19. The number of at-risk centers was also described. RESULTS: Data were recorded from 10,347 institutionalized individuals and up to 4000 health care workers between April 1 and 30, 2020. A rapid increase in suspected cases was seen until day 6 but decreased during the last two weeks (from 1084 to 282 cases). The number of confirmed cases increased from 419 (day 6) to 1293 (day 22) and remained stable during the last week. Of the 10,347 institutionalized individuals, 5,090 (49,2%) remained asymptomatic for ≥14 days. A total of 854/10,347 deaths (8.3%) were reported; 383 of these deaths (44.8%) were suspected/confirmed cases. The number of isolated health care workers remained high over the 30 days, while the number of suspected cases decreased during the last 2 weeks. The number of high-risk long-term care facilities decreased from 19/196 (9.5%) to 3/196 (1.5%). CONCLUSIONS: COVIDApp can help clinicians rapidly detect and remotely monitor suspected and confirmed cases of COVID-19 among institutionalized individuals, thus limiting the risk of spreading the virus. The platform shows the progression of infection in real time and can aid in designing new monitoring strategies.


Subject(s)
Coronavirus Infections/prevention & control , Homes for the Aged , Mobile Applications , Nursing Homes , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Aged , Coronavirus Infections/epidemiology , Diffusion of Innovation , Humans , Long-Term Care , Pneumonia, Viral/epidemiology , Spain/epidemiology
12.
JMIR Public Health Surveill ; 6(3): e20737, 2020 07 21.
Article in English | MEDLINE | ID: covidwho-690354

ABSTRACT

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, social media platforms have become active sites for the dissemination of conspiracy theories that provide alternative explanations of the cause of the pandemic, such as secret plots by powerful and malicious groups. However, the association of individuals' beliefs in conspiracy theories about COVID-19 with mental health and well-being issues has not been investigated. This association creates an assessable channel to identify and provide assistance to people with mental health and well-being issues during the pandemic. OBJECTIVE: Our aim was to provide the first evidence that belief in conspiracy theories regarding the COVID-19 pandemic is a predictor of the mental health and well-being of health care workers. METHODS: We conducted a survey of 252 health care workers in Ecuador from April 10 to May 2, 2020. We analyzed the data regarding distress and anxiety caseness with logistic regression and the data regarding life and job satisfaction with linear regression. RESULTS: Among the 252 sampled health care workers in Ecuador, 61 (24.2%) believed that the virus was developed intentionally in a lab; 82 (32.5%) experienced psychological distress, and 71 (28.2%) had anxiety disorder. Compared to health care workers who were not sure where the virus originated, those who believed the virus was developed intentionally in a lab were more likely to report psychological distress and anxiety disorder and to have lower levels of job satisfaction and life satisfaction. CONCLUSIONS: This paper identifies belief in COVID-19 conspiracy theories as an important predictor of distress, anxiety, and job and life satisfaction among health care workers. This finding will enable mental health services to better target and provide help to mentally vulnerable health care workers during the ongoing COVID-19 pandemic.


Subject(s)
Coronavirus Infections , Coronavirus , Pandemics , Pneumonia, Viral , Betacoronavirus , Cross-Sectional Studies , Ecuador , Health Personnel , Humans , Mental Health , Surveys and Questionnaires
16.
Eur J Phys Rehabil Med ; 56(3): 335-338, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-689752

ABSTRACT

Corona virus disease 2019 (COVID-19) is a new disease characterized by lung damage and involvement in multiple tissues and organs in the whole body. Some of the patients may have long-term impairment and dysfunctions, including pulmonary fibrosis, heart, liver, kidney, nerve and immune system. Rehabilitation has certain beneficial effect in the acute stage, and especially in the recovery stage, including improving respiratory function, exercise endurance, self-care in daily living activities, as well as psychological support, etc. Rehabilitation is not offside or absent. A reasonable rehabilitation program needs scientific research to avoid arbitrary conclusions.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/rehabilitation , Pneumonia, Viral/complications , Pneumonia, Viral/rehabilitation , Activities of Daily Living , China/epidemiology , Coronavirus Infections/epidemiology , Exercise Therapy , Humans , Pandemics , Pneumonia, Viral/epidemiology
18.
Lancet Respir Med ; 8(7): e63-e64, 2020 07.
Article in English | MEDLINE | ID: covidwho-689472
20.
Med Sci Monit ; 26: e925047, 2020 Jul 28.
Article in English | MEDLINE | ID: covidwho-689085

ABSTRACT

BACKGROUND The aim of this study was to describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and compare these parameters in an elderly group with those in a younger group. MATERIAL AND METHODS This retrospective, single-center observational study included 69 hospitalized patients with laboratory-confirmed COVID-19 from a tertiary hospital in Wuhan, China, between January 14, 2020, and February 26, 2020. Epidemiological, demographic, clinical, and laboratory data, as well as treatments, complications, and outcomes were extracted from electronic medical records and compared between elderly patients (aged ≥60 years) and younger patients (aged <60 years). Patients were followed until March 19, 2020. RESULTS Elderly patients had more complications than younger patients, including acute respiratory distress syndrome (ARDS; 9/25, 36% vs. 5/44, 11.4%) and cardiac injury (7/25, 28% vs. 1/44, 2.3%), and they were more likely to be admitted to the intensive care unit (6/25, 24% vs. 2/44, 4.5%). As of March 19, 2020, 60/69 (87%) of the patients had been discharged, 6/69 (8.7%) had died, and 3/69 (4.3%) remained in the hospital. Of those who were discharged or died, the median duration of hospitalization was 13.5 days (interquartile range, 10-18 days). CONCLUSIONS Elderly patients with confirmed COVID-19 were more likely to develop ARDS and cardiac injury than younger patients and were more likely to be admitted to the intensive care unit. In addition to routine monitoring and respiratory support, cardiac monitoring and supportive care should be a focus in elderly patients with COVID-19.


Subject(s)
Age Factors , Coronavirus Infections/epidemiology , Heart Diseases/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Respiratory Distress Syndrome, Adult/epidemiology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Adult , Aged , Aged, 80 and over , Betacoronavirus , China/epidemiology , Combined Modality Therapy , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Heart Diseases/etiology , Humans , Inpatients , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Male , Middle Aged , Multiple Organ Failure/epidemiology , Multiple Organ Failure/etiology , Palliative Care/statistics & numerical data , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Respiratory Distress Syndrome, Adult/etiology , Retrospective Studies , Tertiary Care Centers , Treatment Outcome , Young Adult
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