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1.
PLoS One ; 16(2): e0247367, 2021.
Article in English | MEDLINE | ID: covidwho-1094068

ABSTRACT

This study aimed to identify the specimen type that has high positivity and its proper sampling time for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to promote diagnostic efficiency. All SARS-CoV-2-infected patients with a laboratory-confirmed diagnosis in Zhoushan City were followed up for viral shedding in respiratory tract specimens and faecal samples. Positivity was analysed both qualitatively and quantitatively by proper statistical approaches with strong testing power. Viral shedding in respiratory tract and faecal specimens was prolonged to 45 and 40 days after the last exposure, respectively. The overall positive rate in respiratory tract specimens was low and relatively unstable, being higher in the early-to-mid stage than in the mid-to-late stage of the disease course. Compared with respiratory tract specimens, faecal samples had a higher viral load, higher overall positive rate, and more stable positivity in different disease courses and varied symptomatic status. Faecal specimens have the potential ability to surpass respiratory tract specimens in virus detection. Testing of faecal specimens in diagnosis, especially for identifying asymptomatic carriers, is recommended. Simultaneously, testing respiratory tract specimens at the early-to-mid stage is better than testing at the mid-to-late stage of the disease course. A relatively small sample size was noted, and statistical approaches were used to address it. Information was missing for both specimen types at different stages of the disease course due to censored data. Our research extends the observed viral shedding in both specimen types and highlights the importance of faecal specimen testing in SARS-CoV-2 diagnosis. Healthcare workers, patients, and the general public may all benefit from our study findings. Disposal of sewage from hospitals and residential areas should be performed cautiously because the virus sheds in faeces and can last for a long time.

2.
Clin Infect Dis ; 2021 Feb 17.
Article in English | MEDLINE | ID: covidwho-1087721

ABSTRACT

BACKGROUND: Elucidation of the molecular mechanisms involved in the pathogenesis of coronavirus disease (COVID-19) may help to discover therapeutic targets. METHODS: To determine the metabolomic profile of circulating plasma from COVID-19 survivors with pulmonary sequelae 3 months after discharge, a random, outcome-stratified case-control sample was analyzed. We enrolled 103 recovered COVID-19 patients as well as 27 healthy donors, and performed pulmonary function tests, computerized tomography (CT) scans, laboratory examinations, and liquid chromatography-mass spectrometry. RESULTS: Plasma metabolite profiles of COVID-19 survivors with abnormal pulmonary function were evidently different from those of healthy donors or subjects with normal pulmonary function. These alterations were associated with disease severity and mainly involved amino acid, and glycerophospholipid metabolic pathways. Furthermore, increased levels of triacylglycerols, phosphatidylcholines, prostaglandin E2, arginine, and decreased levels of betain and adenosine were associated with pulmonary CO diffusing capacity and total lung capacity. The global plasma metabolomic profile differed between subjects with abnormal and normal pulmonary function. CONCLUSIONS: Further metabolite-based analysis may help to identify the mechanisms underlying pulmonary dysfunction in COVID-19 survivors, and provide potential therapeutic targets in the future.

3.
Disaster Med Public Health Prep ; : 1-30, 2021 Feb 16.
Article in English | MEDLINE | ID: covidwho-1085458

ABSTRACT

OBJECTIVE: To assess the current status of disease-related knowledge and to analyze the relationship among the general condition, illness perception, and psychological status of patients with COVID-19. METHODS: A hospital-based cross-sectional study was conducted on 118 patients using convenience sampling. The general questionnaire, disease-related knowledge questionnaire of COVID-19, Revised Illness Perception Questionnaire (IPQ-R), and Profile of Mood States (POMS) were used to measure the current status of participants. RESULTS: The overall average score of the disease-related knowledge of patients with COVID-19 was (79.19 ± 14.25), the self-care situation was positively correlated with knowledge of prevention and control (r=0.265, P=0.004) and total score of disease-related knowledge (r= 0.206, P= 0.025); the degree of anxiety was negatively correlated with the knowledge of diagnosis and treatment (r= -0.182, P= 0.049). The score of disease-related knowledge was negatively correlated with negative cognition (volatility, consequences, emotional statements) and negative emotions (tension, fatigue, depression) (P<0.05); positively correlated with positive cognition (disease coherence) and positive emotion (self-esteem) (P<0.05). CONCLUSION: It was recommended that we should pay more attention to the elderly and low-income groups, and increase the knowledge about diagnosis and treatment of COVID-19 and self-care in the future health education for patients.

6.
mBio ; 12(1)2021 01 19.
Article in English | MEDLINE | ID: covidwho-1066818

ABSTRACT

The etiologic agent of COVID-19 is highly contagious and has caused a severe global pandemic. Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for SARS-CoV-2 virologic research and inhibitor screening. In this study, we reported a replicon system which consists of four plasmids expressing the required segments of SARS-CoV-2. Our study revealed that the features for viral RNA synthesis and responses to antivirus drugs of the replicon are similar to those of wild-type viruses. Further analysis indicated that ORF6 provided potent in trans stimulation of the viral replication. Some viral variations, such as 5'UTR-C241T and ORF8-(T28144C) L84S mutation, also exhibit their different impact upon viral replication. Besides, the screening of clinically used drugs identified that several tyrosine kinase inhibitors and DNA-Top II inhibitors potently inhibit the replicon, as well as authentic SARS-CoV-2 viruses. Collectively, this replicon system provides a biosafety-worry-free platform for studying SARS-CoV-2 virology, monitoring the functional impact of viral mutations, and developing viral inhibitors.IMPORTANCE COVID-19 has caused a severe global pandemic. Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for SARS-CoV-2 virologic research and inhibitor screening. We reported a replicon system which consists of four ordinary plasmids expressing the required segments of SARS-CoV-2. Using the replicon system, we developed three application scenarios: (i) to identify the effects of viral proteins on virus replication, (ii) to identify the effects of mutations on viral replication during viral epidemics, and (iii) to perform high-throughput screening of antiviral drugs. Collectively, this replicon system would be useful for virologists to study SARS-CoV-2 virology, for epidemiologists to monitor virus mutations, and for industry to develop antiviral drugs.

7.
Front Med ; 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1053070

ABSTRACT

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.

8.
Autoimmun Rev ; : 102754, 2021 Jan 18.
Article in English | MEDLINE | ID: covidwho-1031877
10.
Sci China Life Sci ; 63(12): 1833-1849, 2020 12.
Article in English | MEDLINE | ID: covidwho-996429

ABSTRACT

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients' outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.


Subject(s)
Antibodies, Viral/biosynthesis , /immunology , /immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/therapeutic use , Asymptomatic Infections , /isolation & purification , China , Drug Development/trends , Host Microbial Interactions/immunology , Humans , Immunity, Humoral , Immunization, Passive , Immunoglobulins, Intravenous/therapeutic use , Models, Immunological , Pandemics , /prevention & control , Seroconversion
11.
IEEE Trans Med Imaging ; PP2020 Dec 16.
Article in English | MEDLINE | ID: covidwho-978666

ABSTRACT

Anomaly detection refers to the identification of cases that do not conform to the expected pattern, which takes a key role in diverse research areas and application domains. Most of existing methods can be summarized as anomaly object detection-based and reconstruction error-based techniques. However, due to the bottleneck of defining encompasses of real-world high-diversity outliers and inaccessible inference process, individually, most of them have not derived groundbreaking progress. To deal with those imperfectness, and motivated by memory-based decision-making and visual attention mechanism as a filter to select environmental information in human vision perceptual system, in this paper, we propose a Multi-scale Attention Memory with hash addressing Autoencoder network (MAMA Net) for anomaly detection. First, to overcome a battery of problems result from the restricted stationary receptive field of convolution operator, we coin the multi-scale global spatial attention block which can be straightforwardly plugged into any networks as sampling, upsampling and downsampling function. On account of its efficient features representation ability, networks can achieve competitive results with only several level blocks. Second, it's observed that traditional autoencoder can only learn an ambiguous model that also reconstructs anomalies "well" due to lack of constraints in training and inference process. To mitigate this challenge, we design a hash addressing memory module that proves abnormalities to produce higher reconstruction error for classification. In addition, we couple the mean square error (MSE) with Wasserstein loss to improve the encoding data distribution. Experiments on various datasets, including two different COVID-19 datasets and one brain MRI (RIDER) dataset prove the robustness and excellent generalization of the proposed MAMA Net.

12.
Clinical Chemistry and Laboratory Medicine ; 58(7):1152-1155, 2020.
Article | WHO COVID | ID: covidwho-976021

ABSTRACT

A retrospective study on complete blood count (CBC) with differential results of patients who presented to the fever clinic of Tongji Hospital with symptoms of COVID-19-like illness between February 1, 2020 and February 20, 2020 was performed through case reviewing Inclusion criteria were fever with a body temperature above 37 3 degreesC, accompanied or not accompanied by cough, chest tightness, muscle ache, shortness of breath and diarrhea Patients with hematopathy, cancer and sepsis were excluded The SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) testing of throat swab was performed in the laboratory of Tongji Hospital These patients with COVID-19-like symptoms were divided into two groups Patients diagnosed with COVID-19 according to the WHO interim guidance and confirmed by RT-PCR testing were included in the SARS-CoV-2-positive patient group (SPPG) Patients with two or more consecutive negative RT-PCR test results were included in the SARS-CoV-2-negative patient group (SNPG) Patients with co-infection of SARS-CoV-2 and other respiratory viruses including influenza A/B, respiratory syncytial virus and adenovirus were also excluded in SPPG Sysmex XN-9000 hematology analyzer was used to obtain the CBC with differential results for patients in each group CBC with differential results at the request of clinicians at the initial evaluations was recorded along with age and gender for each patient Decreased WBC*LYM was observed in SARS-CoV-2-infected patients compared with SARS-CoV-2-negative patients with suspected symptoms in this study WBC*LYM can be used as a supplementary parameter to help clinicians in their first contact with suspected patients awaiting SARS-CoV-2 RT-PCR results

13.
Immunity ; 2020 Nov 25.
Article in English | MEDLINE | ID: covidwho-967948

ABSTRACT

Various vaccine strategies have been proposed in response to the global COVID-19 pandemic, each with unique strategies for eliciting immune responses. Here, we developed nanoparticle vaccines by covalently conjugating the self-assembled 24-mer ferritin to the receptor binding domain (RBD) and/or heptad repeat (HR) subunits of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike (S) protein. Compared to monomer vaccines, nanoparticle vaccines elicited more robust neutralizing antibodies and cellular immune responses. RBD and RBD-HR nanoparticle vaccinated hACE2 transgenic mice vaccinated with RBD and/or RBD-HR nanoparticles exhibited reduced viral load in the lungs after SARS-CoV-2 challenge. RBD-HR nanoparticle vaccines also promoted neutralizing antibodies and cellular immune responses against other coronaviruses. The nanoparticle vaccination of rhesus macaques induced neutralizing antibodies, and T and B cell responses prior to boost immunization; these responses persisted for more than three months. RBD- and HR-based nanoparticles thus present a promising vaccination approach against SARS-CoV-2 and other coronaviruses.

14.
Emerg Microbes Infect ; 9(1): 2571-2577, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-944151

ABSTRACT

Following acute infection, individuals COVID-19 may still shed SARS-CoV-2 RNA. However, limited information is available regarding the active shedding period or whether infectious virus is also shed. Here, we monitored the clinical characteristics and virological features of 38 patients with COVID-19 (long-term carriers) who recovered from the acute disease, but still shed viral RNA for over 3 months. The median carrying history of the long-term carriers was 92 days after the first admission, and the longest carrying history was 118 days. Negative-positive viral RNA-shedding fluctuations were observed. Long-term carriers were mostly elderly people with a history of mild infection. Infectious SARS-CoV-2 was isolated from the sputum, where high level viral RNA was found. All nine full-length genomes of samples obtained in March-April 2020 matched early viral clades circulating in January-February 2020, suggesting that these patients persistently carried SARS-CoV-2 and were not re-infected. IgM and IgG antibodies and neutralizing-antibody profiles were similar between long-term carriers and recovered patients with similar disease courses. In summary, although patients with COVID-19 generated neutralizing antibodies, they may still shed infectious SARS-CoV-2 for over 3 months. These data imply that patients should be monitored after discharge to control future outbreaks.

15.
Molecules ; 25(22)2020 Nov 18.
Article in English | MEDLINE | ID: covidwho-934509

ABSTRACT

Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. In addition, DPP4 binds to the spike protein of the MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulphate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion-exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor-binding domain (RBD) were measured using surface plasmon resonance and ELISA. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected by surface plasmon resonance or ELISA. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS, SARS-CoV-2 does not bind human DPP4.

16.
Emerg Microbes Infect ; 9(1): 2501-2508, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-915844

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a pandemic with increasing numbers of cases worldwide. SARS-CoV-2, the causative virus of COVID-19, is mainly transmitted through respiratory droplets or through direct and indirect contact with an infected person. The possibility of potential faecal-oral transmission was investigated in this study. We collected 258 faecal specimens from nine provinces in China and detected the nucleic acid of SARS-CoV-2 using real-time RT-PCR. Vero cells were used to isolate the virus from SARS-CoV-2 nucleic acid positive samples, after which sequencing of Spike gene in eight samples was performed. In all, 93 of 258 (36%) stool samples were positive for SARS-CoV-2 RNA. The positive rates of critical, severe, moderate, and mild patients were 54.4%, 56.1%, 30.8%, and 33.3%, respectively. The content of nucleic acid increased within 2 weeks after the onset of the disease. From the perspective of clinical typing, the nucleic acid can be detected in the faeces of critical patients within two weeks and until four to five weeks in the faeces of severe and mild patients. SARS-CoV-2 was isolated from stool specimens of two severe patients. Four non-synonymous mutations in Spike gene were newly detected in three stool samples. A small number of patients had strong faecal detoxification ability. The live virus in faeces could be an important source of contamination, which may lead to infection and further spread in areas with poor sanitary conditions. The findings of this study have public health significance and they should be considered when formulating disease control strategies.

17.
Trends Immunol ; 2020 Nov 02.
Article in English | MEDLINE | ID: covidwho-899031

ABSTRACT

A unique feature of the cytokine storm in coronavirus disease 2019 (COVID-19) is the dramatic elevation of interleukin 10 (IL-10). This was thought to be a negative feedback mechanism to suppress inflammation. However, several lines of clinical evidence suggest that dramatic early proinflammatory IL-10 elevation may play a pathological role in COVID-19 severity.

18.
Transbound Emerg Dis ; 2020 Oct 31.
Article in English | MEDLINE | ID: covidwho-894799

ABSTRACT

Since the first two novel coronavirus cases appeared in January of 2020, the outbreak of the COVID-19 epidemic seriously threatens the public health of Italy. In this article, the distribution characteristics and spreading of COVID-19 in various regions of Italy were analysed by heat maps. Meanwhile, spatial autocorrelation, spatiotemporal clustering analysis and kernel density method were also applied to analyse the spatial clustering of COVID-19. The results showed that the Italian epidemic has a temporal trend and spatial aggregation. The epidemic was concentrated in northern Italy and gradually spread to other regions. Finally, the Google Trends index of the COVID-19 epidemic was further employed to build a prediction model combined with machine learning algorithms. By using Adaboost algorithm for single-factor modelling,the results show that the AUC of these six features (mask, pneumonia, thermometer, ISS, disinfection and disposable gloves) are all >0.9, indicating that these features have a large contribution to the prediction model. It is also implied that the public's attention to the epidemic is increasing as well as the awareness of the need for protective measures. This increased awareness of the epidemic will prompt the public to pay more attention to protective measures, thereby reducing the risk of coronavirus infection.

19.
China Tropical Medicine ; 20(9):843-848, 2020.
Article | WHO COVID | ID: covidwho-890726

ABSTRACT

Objective: To understand the current situation of anxiety and depression in hospitalized patients with COVID-19 and suspected patients, and to analyze the influencing factors

20.
PLoS One ; 15(10): e0240285, 2020.
Article in English | MEDLINE | ID: covidwho-874189

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) has swept the whole world with high mortality. Since droplet transmission is the main route of transmission, wearing a mask serves as a crucial preventive measure. However, the virus has spread quite quickly, causing severe mask shortage. Finding alternative materials for homemade masks while ensuring the significant performance indicators will help alleviate the shortage of masks. Referring to the national standard for the "Surgical Mask" of China, 17 materials to be selected for homemade masks were tested in four key indicators: pressure difference, particle filtration efficiency, bacterial filtration efficiency and resistance to surface wetting. Eleven single-layer materials met the standard of pressure difference (≤49 Pa), of which 3 met the standard of resistance to surface wetting (≥3), 1 met the standard of particle filtration efficiency (≥30%), but none met the standard of bacterial filtration efficiency (≥95%). Based on the testing results of single-layer materials, fifteen combinations of paired materials were tested. The results showed that three double-layer materials including double-layer medical non-woven fabric, medical non-woven fabric plus non-woven shopping bag, and medical non-woven fabric plus granular tea towel could meet all the standards of pressure difference, particle filtration efficiency, and resistance to surface wetting, and were close to the standard of the bacterial filtration efficiency. In conclusion, if resources are severely lacking and medical masks cannot be obtained, homemade masks using available materials, based on the results of this study, can minimize the chance of infection to the maximum extent.


Subject(s)
Coronavirus Infections/prevention & control , Disease Transmission, Infectious/prevention & control , Masks/standards , Pandemics/prevention & control , Personal Protective Equipment/standards , Pneumonia, Viral/prevention & control , Textiles/standards , Coronavirus Infections/transmission , Filtration/standards , Humans , Masks/adverse effects , Personal Protective Equipment/adverse effects , Pneumonia, Viral/transmission , Textiles/adverse effects , Textiles/classification
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