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1.
EBioMedicine ; 74: 103712, 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1536515

ABSTRACT

BACKGROUND: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. METHODS: We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. FINDINGS: The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. INTERPRETATION: Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

2.
J Trauma Nurs ; 28(5): 298-303, 2021.
Article in English | MEDLINE | ID: covidwho-1455396

ABSTRACT

BACKGROUND: The high mortality rate of comatose patients with traumatic brain injury is a prominent public health issue that negatively impacts patients and their families. Objective, reliable tools are needed to guide treatment decisions and prioritize resources. OBJECTIVE: This study aimed to evaluate the prognostic value of the bispectral index (BIS) in comatose patients with severe brain injury. METHODS: This was a retrospective cohort study of 84 patients with severe brain injury and Glasgow Coma Scale (GCS) scores of 8 and less treated from January 2015 to June 2017. Sedatives were withheld at least 24 hr before BIS scoring. The BIS value, GCS scores, and Full Outline of UnResponsiveness (FOUR) were monitored hourly for 48 hr. Based on the Glasgow Outcome Scale (GOS) score, the patients were divided into poor (GOS score: 1-2) and good prognosis groups (GOS score: 3-5). The correlation between BIS and prognosis was analyzed by logistic regression, and the receiver operating characteristic curves were plotted. RESULTS: The mean (SD) of the BIS value: 54.63 (11.76), p = .000; and GCS score: 5.76 (1.87), p = .000, were higher in the good prognosis group than in the poor prognosis group. Lower BIS values and GCS scores were correlated with poorer prognosis. Based on the area under the curve of receiver operating characteristic curves, the optimal diagnostic cutoff value of the BIS was 43.6, and the associated sensitivity and specificity were 85.4% and 74.4%, respectively. CONCLUSION: Taken together, our study indicates that BIS had good predictive value on prognosis. These findings suggested that BIS could be used to evaluate the severity and prognosis of severe brain injury.


Subject(s)
Brain Injuries , Coma , Coma/diagnosis , Electroencephalography , Glasgow Coma Scale , Humans , Prognosis , Retrospective Studies
3.
International Journal of Retail & Distribution Management ; 49(11):1512-1531, 2021.
Article in English | ProQuest Central | ID: covidwho-1450494

ABSTRACT

PurposeThe rapid evolution in artificial intelligence (AI) has redefined the customer experience and created huge opportunities for companies to interact with customers using chatbots. This study explores the role of AI chatbots in influencing the online customer experience and customer satisfaction in e-retailing.Design/methodology/approachA research model based on the technology acceptance model and information system success model is proposed to describe the interrelationships among chatbot adoption, online customer experience and customer satisfaction. Personality is a moderator in the model. The authors used a quantitative approach to collect 425 useable online questionnaires and Statistical Product and Service Solutions (SPSS) and SmartPLS to analyze the measurement model and proposed hypotheses.FindingsThe usability of the chatbot had a positive influence on extrinsic values of customer experience, whereas the responsiveness of the chatbot had a positive impact on intrinsic values of customer experience. Furthermore, online customer experience had a positive relationship with customer satisfaction, and personality influenced the relationship between the usability of the chatbot and extrinsic values of customer experience.Originality/valueThis research extends understanding of the online customer experience with chatbots in e-retailing and provides empirical evidence by showing that extrinsic and intrinsic values of online customer experience are enhanced by chatbot adoption.

4.
Cell Rep ; 37(1): 109771, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1439919

ABSTRACT

Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be ∼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Aged , Angiotensin-Converting Enzyme 2/chemistry , Animals , Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/ultrastructure , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody Formation , B-Lymphocytes/immunology , Binding Sites , Chlorocebus aethiops , Cryoelectron Microscopy , HEK293 Cells , Humans , Immunoglobulin Heavy Chains/chemistry , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/immunology , Immunoglobulin Heavy Chains/ultrastructure , Immunoglobulin Light Chains/chemistry , Immunoglobulin Light Chains/genetics , Immunoglobulin Light Chains/immunology , Immunoglobulin Light Chains/ultrastructure , Male , Protein Binding , Protein Interaction Domains and Motifs , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Vero Cells
5.
Methods ; 2021 Sep 23.
Article in English | MEDLINE | ID: covidwho-1433917

ABSTRACT

The coronavirus disease 2019 (COVID-19) has outbreak since early December 2019, and COVID-19 has caused over 100 million cases and 2 million deaths around the world. After one year of the COVID-19 outbreak, there is no certain and approve medicine against it. Drug repositioning has become one line of scientific research that is being pursued to develop an effective drug. However, due to the lack of COVID-19 data, there is still no specific drug repositioning targeting the COVID-19. In this paper, we propose a framework for COVID-19 drug repositioning. This framework has several advantages that can be exploited: one is that a local graph aggregating representation is used across a heterogeneous network to address the data sparsity problem; another is the multi-hop neighbors of the heterogeneous graph are aggregated to recall as many COVID-19 potential drugs as possible. Our experimental results show that our COVDR framework performs significantly better than baseline methods, and the docking simulation verifies that our three potential drugs have the ability to against COVID-19 disease.

6.
Sustainability ; 13(13):7146, 2021.
Article in English | ProQuest Central | ID: covidwho-1304719

ABSTRACT

Previous relevant studies on theme parks lack an exploration of various tourism attributes, e.g., recreational facilities, themes, wait times, fast pass drawings, and pricing, etc., all of which inspired the research motivation of this study. First, the Choice Experiment (CE) method explores tourists’ preferences for theme park attributes. Second, the Conditional Logit (CL) and Random Parameter Logit (RPL) models explore the differences in tourists’ willingness to pay (WTP) for various attributes from the perspective of their socioeconomic background. We used purposive sampling to survey questionnaire answers face-to-face in Taiwan, and a total of 680 questionnaires were issued, of which, 549 copies are valid, with an effective recovery rate of 80.7%. The research findings suggest the following: (1) The most valued theme park attributes for consumers are the recreational facilities, followed by theme characteristics, and fast pass drawing. (2) Regarding the respondents’ WTP for various attributes, they are willing to pay the highest price for thrilling recreational facilities, then for unlimited fast pass services, and cartoon character themes. (3) Respondents believe that if thrilling recreational facilities and fast pass drawing are available at the same time, then the overall effectiveness will be improved. (4) Respondents relatively have no purchase intention for fast pass drawing. It is hoped that the research findings can provide theme park operators reference basis for making plans and decisions.

7.
Complement Ther Med ; 60: 102744, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1252645

ABSTRACT

INTRODUCTION: Chinese patent medicine (CPM) is an indispensable part of traditional Chinese medicine. Coronavirus Disease 2019 (COVID-19) manifests is an acute respiratory infectious disease. This systematic review aimed to evaluate the therapeutic effects and safety of oral CPM for COVID-19. METHODS: We included randomized controlled trials (RCTs) that tested oral CPM for the treatment of COVID-19 identified from publications in CNKI, Wanfang, VIP, Web of Science, SinoMed, PubMed, Embase, BioRxiv, MedRxiv and arXiv before November 2nd, 2020. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool. RESULTS: Seven RCTs including 1079 participants were identified. The overall bias was assessed as "-high risk of bias" for all included trials. Oral CPM investigated were: Lianhua Qingwen capsule/granules (LHQW), Jinhua Qinggan granules (JHQG), Huoxiang Zhengqi dripping pills (HXZQ), Toujie Quwen granules (TJQW) and Lianhua Qingke granules (LHQK). Compared with conventional western therapy alone for people with COVID-19: regarding the main outcomes, the results showed that oral CPM combined with conventional western therapy improved cure rate (RR = 1.20, 95 % CI 1.04-1.38, involving LHQW and TJQW), reduced aggravation rate (RR = 0.50, 95 % CI 0.29 - 0.85, involving LHQW, JHQG, LHQK and TJQW); with regard to additional outcomes, the results showed that add-on oral CPM shortened the duration of fever, cough and fatigue, improved the recovery rate of cough and fatigue, and increased the improvement and recovery rate of chest CT manifestations. There were some differences in therapeutic effects among various CPMs for the same COVID-19 outcome. The use of TJQW and LHQG appeared not to increase the risk of adverse events, but JHQG may cause mild diarrhea. CONCLUSION: Low-certainty or very low-certainty evidence demonstrated that oral CPM may have add-on potential therapeutic effects for patients with non-serious COVID-19. These findings need to be further confirmed by well-designed clinical trials with adequate sample sizes.


Subject(s)
COVID-19/therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Nonprescription Drugs/administration & dosage , Randomized Controlled Trials as Topic , SARS-CoV-2 , Administration, Oral , Bias , Humans
8.
Front Pharmacol ; 11: 583450, 2020.
Article in English | MEDLINE | ID: covidwho-1133942

ABSTRACT

Objective: To present the evidence of the therapeutic effects and safety of Chinese herbal medicine (CHM) used with or without conventional western therapy for COVID-19. Methods: Clinical studies on the therapeutic effects and safety of CHM for COVID-19 were included. We summarized the general characteristics of included studies, evaluated methodological quality of randomized controlled trials (RCTs) using the Cochrane risk of bias tool, analyzed the use of CHM, used Revman 5.4 software to present the risk ratio (RR) or mean difference (MD) and their 95% confidence interval (CI) to estimate the therapeutic effects and safety of CHM. Results: A total of 58 clinical studies were identified including RCTs (17.24%, 10), non-randomized controlled trials (1.72%, 1), retrospective studies with a control group (18.97%, 11), case-series (20.69%, 12) and case-reports (41.38%, 24). No RCTs of high methodological quality were identified. The most frequently tested oral Chinese patent medicine, Chinese herbal medicine injection or prescribed herbal decoction were: Lianhua Qingwen granule/capsule, Xuebijing injection and Maxing Shigan Tang. In terms of aggravation rate, pooled analyses showed that there were statistical differences between the intervention group and the comparator group (RR 0.42, 95% CI 0.21 to 0.82, six RCTs; RR 0.38, 95% CI 0.23 to 0.64, five retrospective studies with a control group), that is, CHM plus conventional western therapy appeared better than conventional western therapy alone in reducing aggravation rate. In addition, compared with conventional western therapy, CHM plus conventional western therapy had potential advantages in increasing the recovery rate and shortening the duration of fever, cough and fatigue, improving the negative conversion rate of nucleic acid test, and increasing the improvement rate of chest CT manifestations and shortening the time from receiving the treatment to the beginning of chest CT manifestations improvement. For adverse events, pooled data showed that there were no statistical differences between the CHM and the control groups. Conclusion: Current low certainty evidence suggests that there maybe a tendency that CHM plus conventional western therapy is superior to conventional western therapy alone. The use of CHM did not increase the risk of adverse events.

9.
Front Pharmacol ; 11: 609592, 2020.
Article in English | MEDLINE | ID: covidwho-1094200

ABSTRACT

To identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. The combination of Clomiphene (citrate), Vortioxetine and Asenapine (hydrochloride) is much more potent than used alone, with IC50 of 0.34 µM.

13.
J Immunother Cancer ; 8(2)2020 12.
Article in English | MEDLINE | ID: covidwho-971586

ABSTRACT

The COVID-19 outbreak caused by SARS-CoV-2 challenges the medical system by interfering with routine therapies for many patients with chronic diseases. In patients with cancer receiving immune checkpoint inhibitors (ICIs), difficulties also arise from the incomplete understanding of the intricate interplay between their routine treatment and pathogenesis of the novel virus. By referring to previous ICI-based investigations, we speculate that ICIs themselves are not linked to high-infection risks of respiratory diseases or inflammation-related adverse effects in patients with cancer. Moreover, ICI treatment may even enhance coronavirus clearance in some patients with malignant tumor by boosting antiviral T-cell responsiveness. However, the 'explosive' inflammation during COVID-19 in some ICI-treated patients with cancer was illustrated as exuberant immunopathological damage or even death. In case of the COVID-19 immunopathogenesis fueled by ICIs, we propose a regular monitor of pathogenic T-cell subsets and their exhaustion marker expression (eg, Th17 and interleukin (IL)-6-producing Th1 subsets with surface programmed death 1 expression) to guide the usage of ICI. Here we aimed to address these considerations, based on available literature and experience from our practice, that may assist with the decision-making of ICI administration during the pandemic.


Subject(s)
Antineoplastic Agents, Immunological/pharmacology , COVID-19/immunology , Cytokine Release Syndrome/prevention & control , Neoplasms/drug therapy , SARS-CoV-2/immunology , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Clinical Decision-Making , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Drug Monitoring , Humans , Lung/diagnostic imaging , Neoplasms/blood , Neoplasms/immunology , Pandemics , Patient Selection , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , SARS-CoV-2/isolation & purification , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/metabolism , Th17 Cells/drug effects , Th17 Cells/immunology , Th17 Cells/metabolism , Tomography, X-Ray Computed
14.
Zhongguo Zhen Jiu ; 40(10): 1027-33, 2020 Oct 12.
Article in Chinese | MEDLINE | ID: covidwho-874969

ABSTRACT

OBJECTIVE: To establish and promote the non-contact doctor-patient interactive diagnosis and treatment mode based on mobile internet for the treatment of coronavirus disease 2019 (COVID-19) with moxibustion therapy, and to observe the feasibility and effectiveness of the model in the pandemic. METHODS: A total of 43 first-line medical staff and 149 suspected and confirmed cases with COVID-19 [18 cases in medical observation period, 17 cases of mild type (cold dampness and stagnation in the lung), 24 cases of ordinary type (cold-dampness accumulated in the lung) and 90 cases in recovery period (qi deficiency of spleen and lung)] were included. A non-contact doctor-patient interactive diagnosis and treatment platform was established for the treatment of COVID-19 with indirect moxibustion plaster based on mobile internet. By the platform, the patients were instructed to use indirect moxibustion plaster in treatment. For the first-line medical staff and patients in the medical observation period, Zusanli (ST 36), Qihai (CV 6) and Zhongwan (CV 12) were selected. For the mild cases (cold dampness and stagnation in the lung) and the cases of ordinary type (cold-dampness accumulated in the lung), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Guanyuan (CV 4) were selected. In the recovery period (qi deficiency of spleen and lung), Dazhui (GV 14), Feishu (BL 13), Geshu (BL 17), Zusanli (ST 36) and Kongzui (LU 6) were used. The treatment was given once daily for 40 min each time. The intervention lasted for 10 days. After intervention, the infection rate and the improvement in the symptoms and psychological status of COVID-19 were observed in clinical first-line medical staff and COVID-19 patients. RESULTS: In 10 days of intervention with indirect moxibustion plaster, there was "zero" infection among medical staff. Of 43 first-line physicians and nurses, 33 cases had some physical symptoms and psychological discomforts, mainly as low back pain, poor sleep and anxiety. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 78.8% (26/33) and the curative rate was 36.4% (12/33). Regarding the improvements in psychological discomforts, the effective rate was 58.3% (14/24) and the curative rate was 37.5 (9/24). Of 149 patients, 133 cases had the symptoms and psychological discomforts. After treatment, regarding the improvements in the symptoms and psychological discomforts, the effective rate was 81.2% (108/133) and the curative rate was 34.6% (46/133). Regarding the improvements in psychological discomforts, the effective rate was 76.5% (52/68) and the curative rate was 57.4 % (39/68). CONCLUSION: It is feasible to apply the indirect moxibustion plaster technique based on mobile internet to the treatment COVID-19. This mode not only relieves the symptoms such as cough and fatigue, improves psychological state, but also possibly prevents the first-line medical staff from COVID-19.


Subject(s)
Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Moxibustion , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Remote Consultation , Acupuncture Points , Betacoronavirus , COVID-19 , Health Personnel , Humans , SARS-CoV-2
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