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1.
Frontiers in psychiatry ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1990150

ABSTRACT

Background Published studies in comparing pre and post the COVID-19 pandemic depression and anxiety levels among children and adolescents yielded incongruent results. Therefore, there is a necessity to perform a timely meta-analysis to synthesize existing evidence. Methods A total of 10 digital databases (PubMed, Web of Science, PsycINFO, the Cochrane Library, Embase, Scopus, ScienceDirect, CNKI, WanFang, CQVIP) were fully searched for eligible studies published before November 6, 2021. Based on quality assessment results, relevant data were extracted for eligible studies of higher quality. We combined standardized mean difference (SMD) or prevalence ratio (RR) for anxiety and depression pre and post the COVID-19 pandemic by using random-effects models. Sensitivity analysis was further performed to evaluate heterogeneity of included studies. Results 14,508 articles were preliminarily identified, and after stepwise screening process, 8 articles were included eventually. The results showed that the SMD for post COVID-19 anxiety score measured by GAD-7 was 0.12 (95% CI: 0.08, 0.17), an significant increase compared with pre COVID-19 period;the SMDs and 95% CIs for post COVID-18 depression scores measured by PHQ-9, PHQ-8, and MFQ were 0.17 (95% CI: 0.10, 0.24), 0.23 (95% CI: 0.08, 0.38), and 0.11 (95% CI: 0.06, 0.17), respectively, also significantly increased compared with pre COVID-19 period. The RR for depression was 2.54 (95% CI: 2.48, 2.60) in post COVID-19 period when compared with pre-pandemic. Conclusions Children and adolescents reported deteriorated anxiety and depression levels after the COVID-19 pandemic. More attention should be paid to this vulnerable group. Effective, expedient, and practical intervention measures which are compatible with COVID-19 prevention and control policies should be developed and implemented to maintain mental health wellbeing of the youths.

2.
Eur J Med Chem ; 238: 114458, 2022 Aug 05.
Article in English | MEDLINE | ID: covidwho-1982956

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), as the pathogen of coronavirus disease 2019 (COVID-19), has infected millions of people and took hundreds of thousands of lives. Unfortunately, there is deficiency of effective medicines to prevent or treat COVID-19. 3C like protease (3CLPro) of SARS-CoV-2 is essential to the viral replication and transcription, and is an attractive target to develop anti-SARS-CoV-2 agents. Targeting on the 3CLPro, we screened our protease inhibitor library and obtained compound 10a as hit to weakly inhibit the SARS-CoV-2 3CLPro, and determined the co-crystal structure of 10a and the protease. Based on the deep understanding on the protein-ligand complexes between the hit and SARS-CoV-2 3CLPro, we designed a series of peptidomimetic inhibitors, with outstanding inhibitory activity against SARS-CoV-2 3CLPro and excellent anti-viral potency against SARS-CoV-2. The protein-ligand complexes of the other key inhibitors with SARS-CoV-2 3CLPro were explicitly described by the X-ray co-crystal study. All such results suggest these peptidomimetic inhibitors could be further applied as encouraging drug candidates.


Subject(s)
COVID-19 , Peptidomimetics , Antiviral Agents/chemistry , COVID-19/drug therapy , Cysteine Endopeptidases/chemistry , Humans , Ligands , Peptide Hydrolases , Peptidomimetics/chemistry , Peptidomimetics/pharmacology , Protease Inhibitors/chemistry , SARS-CoV-2
3.
Virol Sin ; 2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1915075

ABSTRACT

Several variants of concern (VOCs) have emerged since the WIV04 strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first isolated in January 2020. Due to mutations in the spike (S) protein, these VOCs have evolved to enhance viral infectivity and immune evasion. However, whether mutations of the other viral proteins lead to altered viral propagation and drug resistance remains obscure. The replicon is a noninfectious viral surrogate capable of recapitulating certain steps of the viral life cycle. Although several SARS-CoV-2 replicons have been developed, none of them were derived from emerging VOCs and could only recapitulate viral genome replication and subgenomic RNA (sgRNA) transcription. In this study, SARS-CoV-2 replicons derived from the WIV04 strain and two VOCs (the Beta and Delta variants) were prepared by removing the S gene from their genomes, while other structural genes remained untouched. These replicons not only recapitulate viral genome replication and sgRNA transcription but also support the assembly and release of viral-like particles, as manifested by electron microscopic assays. Thus, the S-deletion replicon could recapitulate virtually all the post-entry steps of the viral life cycle and provides a versatile tool for measuring viral intracellular propagation and screening novel antiviral drugs, including inhibitors of virion assembly and release. Through the quantification of replicon RNA released into the supernatant, we demonstrate that viral intracellular propagation and drug response to remdesivir have not yet substantially changed during the evolution of SARS-CoV-2 from the WIV04 strain to the Beta and Delta VOCs.

4.
Biomed Signal Process Control ; 78: 103889, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1906821

ABSTRACT

In order to aid imaging physicians to effectively screen chest radiography medical images for presence of Coronavirus Disease 2019 (COVID-19), a novel computer aided diagnosis technology for automatic processing of COVID-19 images is proposed based on two-dimensional variational mode decomposition (2D-VMD) and locally linear embedding (LLE). 2D-VMD algorithm is used to decompose normal and COVID-19 images, and then feature extraction of intrinsic mode functions (IMFs) using Gabor filter. To better extract low-dimensional parameters which are useful for COVID-19 diagnosis, the performance of two dimensionality reduction techniques of principal component analysis (PCA) and LLE are compared, and the LLE is shown to offer satisfactory effect of dimension reduction. Thereafter, the particle swarm optimization-support vector machine (PSO-SVM) algorithm is used to classify. The simulation results show that the proposed technology has achieved accuracy of 99.33%, precision of 100%, recall of 98.63% and F-Measure of 99.31%. Hence, the developed diagnosis technology can be used as an important auxiliary tool to assist diagnosis of imaging physicians.

5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330371

ABSTRACT

Population antibody response is believed to be important in selection of new variant viruses. We identified that SARS-CoV-2 infections elicit a population immune response mediated by a lineage of VH1-69 germline antibodies. The representative antibody R1-32 targets a novel semi-cryptic epitope defining a new class of RBD targeting antibodies. Binding to this non-ACE2 competing epitope leading to spike destruction impairing virus entry. Based on epitope location, neutralization mechanism and analysis of antibody binding to spike variants we propose that recurrent substitutions at 452 and 490 are associated with immune evasion of this population antibody response. These substitutions, including L452R found in the Delta variant, disrupt interaction mediated by the VH1-69 specific hydrophobic HCDR2 to impair antibody-antigen association allowing variants to escape. Lacking 452/490 substitutions, the Omicron variant is sensitive to this class of antibodies. Our results provide new insights into SARS-CoV-2 variant genesis and immune evasion.

6.
Front Cell Infect Microbiol ; 11: 706970, 2021.
Article in English | MEDLINE | ID: covidwho-1581382

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause gastrointestinal symptoms in the patients, but the role of gut microbiota in SARS-CoV-2 infection remains unclear. Thus, in this study, we aim to investigate whether SARS-CoV-2 infection affects the composition and function of gut microbiota. In this study, we demonstrated for the first time that significant shifts in microbiome composition and function were appeared in both SARS-CoV-2-infected asymptomatic and symptomatic cases. The relative abundance of Candidatus_Saccharibacteria was significantly increased, whereas the levels of Fibrobacteres was remarkably reduced in SARS-CoV-2-infected cases. There was one bacterial species, Spirochaetes displayed the difference between patients and asymptomatic cases. On the genus level, Tyzzerella was the key species that remarkably increased in both symptomatic and asymptomatic cases. Analyses of genome annotations further revealed SARS-CoV-2 infection resulted in the significant 'functional dysbiosis' of gut microbiota, including metabolic pathway, regulatory pathway and biosynthesis of secondary metabolites etc. We also identified potential metagenomic markers to discriminate SARS-CoV-2-infected symptomatic and asymptomatic cases from healthy controls. These findings together suggest gut microbiota is of possible etiological and diagnostic importance for SARS-CoV-2 infection.


Subject(s)
COVID-19 , Dysbiosis , Humans , Metagenome , Metagenomics , SARS-CoV-2
7.
Front Bioeng Biotechnol ; 9: 773304, 2021.
Article in English | MEDLINE | ID: covidwho-1574661

ABSTRACT

The COVID-19 pandemic has resulted in significant global social and economic disruption. The highly transmissive nature of the disease makes rapid and reliable detection critically important. Point-of-care (POC) tests involve performing diagnostic tests outside of a laboratory that produce a rapid and reliable result. It therefore allows the diagnostics of diseases at or near the patient site. Paper-based POC tests have been gaining interest in recent years as they allow rapid, low-cost detection without the need for external instruments. In this review, we focus on the development of paper-based POC devices for the detection of SARS-CoV-2. The review first introduces the principles of detection methods that are available to paper-based devices. It then summarizes the state-of-the-art paper devices and their analytical performances. The advantages and drawbacks among methods are also discussed. Finally, limitations of the existing devices are discussed, and prospects are given with the hope to identify research opportunities and directions in the field. We hope this review will be helpful for researchers to develop a clinically useful and economically efficient paper-based platform that can be used for rapid, accurate on-site diagnosis to aid in identifying acute infections and eventually contain the COVID-19 pandemic.

8.
Carbohydr Polym ; 275: 118779, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-1466086

ABSTRACT

Previous researches suggested that polysaccharides from brown algae had anti-virus activity. We hypothesized that nature polysaccharide from marine plants might have the effect on anti-SARS-CoV-2 activity. By high throughput screening to target 3CLpro enzyme using polysaccharides library, we discover a crude polysaccharide 375 from seaweed Ecklonia kurome blocked 3CLpro enzymatic activity and shows good anti-SARS-CoV-2 infection activity in cell. Further, we show that homogeneous polysaccharide 37502 from the 375 may bind to 3CLpro well and disturb spike protein binding to ACE2 receptor. The structure characterization uncovers that 37502 is alginate. These results imply that the bioactivities of 375 on SARS-CoV-2 may target multiple key molecules implicated in the virus infection and replication. The above results suggest that 375 may be a potential drug candidate against SARS-CoV-2.


Subject(s)
COVID-19 , Polysaccharides , Humans , Molecular Docking Simulation , Seaweed/chemistry , Virus Internalization/drug effects
9.
Res Pract Thromb Haemost ; 5(6): e12596, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1414996

ABSTRACT

Adenoviral-vector based vaccines for coronavirus disease 2019 (COVID-19) have been linked with a thrombotic syndrome, vaccine-induced thrombotic thrombocytopenia (VITT). A key clinical question is whether VITT can be reliably ruled out by the absence of thrombocytopenia. We report on three patients who presented to our institute with this syndrome. Noteworthy in our presentations are two patients who presented for medical assessment of thrombotic symptoms with a normal platelet count, one preceding and one following a period of thrombocytopenia. Prompt diagnosis of VITT is critical to prevent rapid patient decline. We provide herein a new diagnostic algorithm that we believe will help optimally capture case presentations of VITT. These cases broaden and refine our understanding of the disease process and highlight to practitioners that VITT cannot be adequately ruled out by thrombocytopenia alone.

10.
IEEE Trans Comput Soc Syst ; 8(6): 1302-1310, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1225654

ABSTRACT

Precision mitigation of COVID-19 is in pressing need for postpandemic time with the absence of pharmaceutical interventions. In this study, the effectiveness and cost of digital contact tracing (DCT) technology-based on-campus mitigation strategy are studied through epidemic simulations using high-resolution empirical contact networks of teachers and students. Compared with traditional class, grade, and school closure strategies, the DCT-based strategy offers a practical yet much more efficient way of mitigating COVID-19 spreading in the crowded campus. Specifically, the strategy based on DCT can achieve the same level of disease control as rigid school suspensions but with significantly fewer students quarantined. We further explore the necessary conditions to ensure the effectiveness of DCT-based strategy and auxiliary strategies to enhance mitigation effectiveness and make the following recommendation: social distancing should be implemented along with DCT, the adoption rate of DCT devices should be assured, and swift virus tests should be carried out to discover asymptomatic infections and stop their subsequent transmissions. We also argue that primary schools have higher disease transmission risks than high schools and, thereby, should be alerted when considering reopenings.

11.
Cell Discov ; 7(1): 31, 2021 May 04.
Article in English | MEDLINE | ID: covidwho-1216454

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 pandemic. How SARS-CoV-2 regulates cellular responses to escape clearance by host cells is unknown. Autophagy is an intracellular lysosomal degradation pathway for the clearance of various cargoes, including viruses. Here, we systematically screened 28 viral proteins of SARS-CoV-2 and identified that ORF3a strongly inhibited autophagic flux by blocking the fusion of autophagosomes with lysosomes. ORF3a colocalized with lysosomes and interacted with VPS39, a component of the homotypic fusion and protein sorting (HOPS) complex. The ORF3a-VPS39 interaction prohibited the binding of HOPS with RAB7, which prevented the assembly of fusion machinery, leading to the accumulation of unfused autophagosomes. These results indicated the potential mechanism by which SARS-CoV-2 escapes degradation; that is, the virus interferes with autophagosome-lysosome fusion. Furthermore, our findings will facilitate strategies targeting autophagy for conferring potential protection against the spread of SARS-CoV-2.

12.
Biomolecules ; 11(2)2021 01 30.
Article in English | MEDLINE | ID: covidwho-1055018

ABSTRACT

The epidemic due to the novel coronavirus (SARS-CoV-2) is now a global concern, posing a severe threat to the health of populations. At present, all countries in the world are stepping up the development of vaccines and antiviral agents to prevent the infection and further transmission of SARS-CoV-2. An in-depth investigation of the target organs and pathogenesis regarding SARS-CoV-2 infection will be beneficial for virus therapy. Besides pulmonary injury, SARS-CoV-2 also causes cardiac injury, but the exact mechanisms are unclear. This review summarizes the essential structural characteristics of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2), describes the cardiac manifestations following SARS-CoV-2 infection, and explores the mechanisms of cardiac injury targeting ACE2 after the viral invasion. We aim to help the timely detection of related symptoms and implementation of therapeutic measures by clinicians for SARS-CoV-2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2/drug effects , COVID-19/physiopathology , Heart Diseases/etiology , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/physiology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , COVID-19/virology , Drug Delivery Systems , Early Diagnosis , Genome, Viral , Heart Diseases/diagnosis , Humans , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
13.
Protein Cell ; 12(9): 717-733, 2021 09.
Article in English | MEDLINE | ID: covidwho-973695

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.


Subject(s)
Alveolar Epithelial Cells/metabolism , COVID-19/pathology , Lung/metabolism , SARS-CoV-2/physiology , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Alveolar Epithelial Cells/cytology , Alveolar Epithelial Cells/virology , Antibodies, Neutralizing/pharmacology , Antibodies, Neutralizing/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Down-Regulation , Drug Discovery , Human Embryonic Stem Cells/cytology , Human Embryonic Stem Cells/metabolism , Humans , Immunity , Lipid Metabolism , Lung/cytology , Lung/virology , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Virus Replication/drug effects
14.
Brief Bioinform ; 22(3)2021 05 20.
Article in English | MEDLINE | ID: covidwho-787100

ABSTRACT

Recent advances in transcriptomics have uncovered lots of novel transcripts in plants. To annotate such transcripts, dissecting their coding potential is a critical step. Computational approaches have been proven fruitful in this task; however, most current tools are designed/optimized for mammals and only a few of them have been tested on a limited number of plant species. In this work, we present NAMS webserver, which contains a novel coding potential classifier, NAMS, specifically optimized for plants. We have evaluated the performance of NAMS using a comprehensive dataset containing more than 3 million transcripts from various plant species, where NAMS demonstrates high accuracy and remarkable performance improvements over state-of-the-art software. Moreover, our webserver also furnishes functional annotations, aiming to provide users informative clues to the functions of their transcripts. Considering that most plant species are poorly characterized, our NAMS webserver could serve as a valuable resource to facilitate the transcriptomic studies. The webserver with testing dataset is freely available at http://sunlab.cpy.cuhk.edu.hk/NAMS/.


Subject(s)
Computational Biology/methods , Gene Expression Profiling/methods , Gene Expression Regulation, Plant , Internet , Molecular Sequence Annotation/methods , Plants/genetics , Genetic Code/genetics , Plants/classification , RNA, Messenger/genetics , RNA, Plant/genetics , Reproducibility of Results , Species Specificity , Support Vector Machine
15.
Am J Emerg Med ; 38(10): 2101-2109, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-696758

ABSTRACT

INTRODUCTION: Influenza has been linked to the crowding in emergency departments (ED) across the world. The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on China EDs has been quite different from those during past influenza outbreaks. Our objective was to determine if COVID-19 changed ED visit disease severity during the pandemic. METHODS: This was a retrospective cross sectional study conducted in Nanjing, China. We captured ED visit data from 28 hospitals. We then compared visit numbers from October 2019 to February 2020 for a month-to-month analysis and every February from 2017 to 2020 for a year-to-year analysis. Inter-group chi-square test and time series trend tests were performed to compare visit numbers. The primary outcome was the proportion of severe disease visits in the EDs. RESULTS: Through February 29 th 2020, there were 93 laboratory-confirmed COVID-19 patients in Nanjing, of which 40 cases (43.01%) were first seen in the ED. The total number of ED visits in Nanjing in February 2020, were dramatically decreased (n = 99,949) in compared to January 2020 (n = 313,125) and February 2019 (n = 262,503). Except for poisoning, the severe diseases in EDs all decreased in absolute number, but increased in proportion both in year-to-year and month-to-month analyses. This increase in proportional ED disease severity was greater in higher-level referral hospitals when compared year by year. CONCLUSION: The COVID-19 outbreak has been associated with decreases in ED visits in Nanjing, China, but increases in the proportion of severe ED visits.


Subject(s)
COVID-19/epidemiology , Emergency Service, Hospital/statistics & numerical data , Severity of Illness Index , China/epidemiology , Critical Illness/epidemiology , Cross-Sectional Studies , Humans , Pandemics , Retrospective Studies , SARS-CoV-2
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