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6.
ssrn; 2024.
Preprint em Inglês | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.4739813

Assuntos
COVID-19
7.
ssrn; 2024.
Preprint em Inglês | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.4730790
10.
ssrn; 2024.
Preprint em Inglês | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.4737718
11.
biorxiv; 2024.
Preprint em Inglês | bioRxiv | ID: ppzbmed-10.1101.2024.02.28.582665

RESUMO

A novel concept titled Peptide Mold for mapping potential binding sites in protein targets is presented. A large multiconformer tetrapeptide library comprising of 32 million conformations of all possible combinations of naturally-occurring amino acids was constructed and used for molecular docking analysis in the substrate-binding site of SARS-CoV-2 PLpro enzyme. The top-ranking, structurally-diverse tetrapeptide docked conformations (symbolizing peptide mold, analogous to a clay mold) were used then for elucidating a five-point pharmacophore. Ligand-based virtual screening of a large, multiconformer library of phytoconstituents using the derived five-point pharmacophore led to identification of potential binders for SARS-CoV-2 PLpro at its substrate-binding site. The approach is based on generating the imprint of a macromolecular binding site (cavity) using tetrapeptides (clay), thereby generating a reverse mold (with definitive shape and size), which can further be used for identifying small-molecule ligands matching the captured features of the target binding site. The approach is based on the fact that the individual amino acids in the tetrapeptide represent all possible drug-receptor interaction features (electrostatic, H-bonding, van der Waals, dispersion and hydrophobic among others). The peptide mold approach can be extended to any protein target for mapping the binding site(s), and further use of the generated pharmacophore model for virtual screening of potential binders. The peptide mold approach is a robust, hybrid computational screening strategy, overcoming the present limitations of structure-based methods, e.g., molecular docking and the ligand-based methods such as pharmacophore search. Exploration of the peptide mold strategy is expected to yield high-quality, reliable and interesting virtual hits in the computational screening campaigns during the hit and lead identification stages.

12.
biorxiv; 2024.
Preprint em Inglês | bioRxiv | ID: ppzbmed-10.1101.2024.02.28.582613

RESUMO

Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection from disease progression. Non-neutralizing antibodies cannot directly protect from infection but may recruit effector cells thus contribute to the clearance of infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs from COVID-19 vaccinated individuals. Most of these antibodies exhibited no neutralizing activity in vitro but several non-neutralizing antibodies protected against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs showed a clear dependence on Fc-mediated effector functions. We determined the structures of three non-neutralizing antibodies with two targeting the RBD, and one that targeting the SD1 region. Our data confirms the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.


Assuntos
COVID-19
13.
biorxiv; 2024.
Preprint em Inglês | bioRxiv | ID: ppzbmed-10.1101.2024.02.28.582480

RESUMO

SARS-CoV-2 pandemic alerts us that spillovers of various animal coronaviruses to human in the future may bring us enormous damages. Thus, there is a significant need of antibody-based drugs to treat patients infected with previously unseen coronaviruses. CV804 against the S2 domain of the spike protein, which is less prone to mutations. CV804 shows not only broad cross-reactivities with representative 20 animal-origin coronaviruses but also with diseases-associated human beta coronaviruses including SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-HKU1 and mutant strains of SARS-CoV-2. Other than that, the main characteristics of CV804 are that it has strong antibody-dependent cellular cytotoxicity (ADCC) activity to SARS-CoV2 spike protein-expressed cells in vitro and completely lacks virus-neutralization activity. Comprehensively in animal models, CV804 suppressed disease progression by SARS-CoV-2 infection. Structural studies using HDX-MS and point mutations of recombinant spike proteins revealed that CV804 binds to a unique epitope within the highly conserved S2 domain of the spike proteins of various coronaviruses. Based on the overall data, we suggest that the non-neutralizing CV804 antibody recognizes the conformational structure of the spike protein expressed on the surface of the infected cells and weakens the viral virulence by supporting host immune cells attack through ADCC activity in vivo. CV804 epitope identified in this study is not only useful for the design of pan-corona antibody therapeutics but also to design next-generation coronavirus vaccines and antiviral drugs.


Assuntos
Síndrome Respiratória Aguda Grave , COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
14.
preprints.org; 2024.
Preprint em Inglês | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202402.1752.v1

RESUMO

International students were – and continue to be – particularly vulnerable to the negative consequences of the COVID-19 pandemic. 625 international students in Israel completed an online survey assessing risk and protective factors (socio-demographics, health status, COVID-19 related experiences/concerns, financial difficulties, academic challenges/experiences, social support, and coping) for student’s depression, perceived need for help, and seeking help from the university. Approximately 15% of participants had moderately-severe or severe depression. Over half needed at least a little help, but only 19.7% had asked for help. Depression symptoms were related coping (β=-.34) and health (β=.12). Need for help was related to being a postdoc (β=-0.26) and experiencing food insecurity (β=0.20). Universities need to develop services which address international students’ unique needs during global crises.


Assuntos
Transtorno Depressivo , COVID-19
15.
arxiv; 2024.
Preprint em Inglês | PREPRINT-ARXIV | ID: ppzbmed-2402.19280v1

RESUMO

More than six million people died of the COVID-19 by April 2022. The heavy casualties have put people on great and urgent alert and people try to find all kinds of information to keep them from being inflected by the coronavirus. This research tries to find out whether the mobile health text information sent to peoples devices is correct as smartphones becoming the major information source for people. The proposed method uses various mobile information retrieval and data mining technologies including lexical analysis, stopword elimination, stemming, and decision trees to classify the mobile health text information to one of the following classes: (i) true, (ii) fake, (iii) misinformative, (iv) disinformative, and (v) neutral. Experiment results show the accuracy of the proposed method is above the threshold value 50 percentage, but is not optimal. It is because the problem, mobile text misinformation identification, is intrinsically difficult.


Assuntos
COVID-19
16.
medrxiv; 2024.
Preprint em Inglês | medRxiv | ID: ppzbmed-10.1101.2024.02.27.24303454

RESUMO

Introduction:   Pregnant women are considered a high-risk group for COVID-19, and a priority for vaccination. Routine antenatal (ANC) care provides an opportunity to track trends and factors associated with vaccine uptake. We sought to evaluate COVID-19 vaccine uptake among pregnant women attending ANC in Zambia.   Methods  We conducted a repeated cross-sectional study in 39 public health facilities in four districts in Zambia from September 2021 to September 2022. Pregnant women who were aged 15-49 years were enrolled during their first ANC visit. Every month, ~20 women per facility were interviewed during individual HIV testing and counseling. We estimated vaccine uptake as the proportion of eligible participants who self-reported having received the COVID-19 vaccine.   Results   A total of 9,203 pregnant women were screened, of which 9,111 (99%) were eligible and had vaccination status. Of the 9,111 included in the analysis, 1,818 (20%) had received the COVID-19 vaccine during the study period, with a trend of increasing coverage with time (0.5% in September 2020, 27% in September 2022). Conversely, 3,789 (42%) reported not being offered a COVID-19 vaccine. We found that older age, education, employment status, and prior COVID-19 infection were significantly associated with vaccine uptake.     Conclusion  COVID-19 vaccine uptake among pregnant women was lower than estimates from the general population (27% across the four districts in September 2022), pointing to missed opportunities to protect this high-risk group. ANC visits were a viable point for conducting COVID-19 surveillance. Incorporating the vaccine as part of the routine ANC package might increase coverage in this group.


Assuntos
COVID-19
17.
medrxiv; 2024.
Preprint em Inglês | medRxiv | ID: ppzbmed-10.1101.2024.02.28.24303505

RESUMO

Background: For pathogens which cause infections that present asymptomatically, evaluating vaccine efficacy (VE) against asymptomatic infection is important for understanding a vaccine's potential epidemiological impact. Regular testing for subclinical infections is a potentially valuable strategy but its success hinges on participant adherence and minimising false positives. This paper describes the implementation and adherence to weekly testing in a COVID-19 vaccine trial. Methods: COV002 was a phase 2/3 trial assessing the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2. Asymptomatic infections were detected using weekly self-administered swabs for RT-PCR testing. We analysed adherence using mixed-effects regression models and estimated the probability of true and false positive asymptomatic infections using estimates of adherence and testing characteristics. Findings: 356,551 tests were self-administered by 10,811 participants during the 13-month follow-up. Median adherence was 75.0% (IQR 42.6-90.9), which translated to a 74.5% (IQR 50.9-78.8) probability of detecting a positive asymptomatic infection during the swabbing period, and between 21 and 96 false positives during VE evaluation. The odds of returning a swab declined by 8% per week and further after testing positive and unblinding. Adherence was higher in older age groups, females and non-healthcare workers. Interpretation The COV002 trial demonstrated the feasibility of running a long-term regular asymptomatic testing strategy. This information could be valuable for designing future phase III vaccine trials in which infection is an outcome. Funding UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, AstraZeneca.


Assuntos
COVID-19
18.
medrxiv; 2024.
Preprint em Inglês | medRxiv | ID: ppzbmed-10.1101.2024.02.27.24303073

RESUMO

Background: In Germany, most patients with coronavirus disease 2019 (COVID-19) are treated in an outpatient setting. To improve assessments of the health status of COVID-19 outpatients, various remote monitoring models have been developed. However, little information exists on experiences acquired with remote monitoring in an outpatient setting, particularly from a patient perspective. The aim of our 'COVID-19@home' study was therefore to implement and evaluate an app-based remote monitoring concept for acute and post-acute COVID-19-patients in primary care. In this paper, we focus on the patients' evaluation of our remote monitoring approach. Methods Patients with acute COVID-19 measured heart rate, blood pressure, oxygen saturation, and body temperature daily for 28 days. Patients with post-acute COVID-19 determined the same parameters for 12 weeks, supplemented by lung parameters and daily step count. The data were documented using the 'SaniQ' smartphone app. COVID-19 symptoms were assessed daily using an app-based questionnaire. Patients' GPs could access the data on the 'SaniQ Praxis' telemedicine platform. We used an app-based questionnaire consisting of 11 questions presented with a 4-point Likert scale to evaluate patient satisfaction. Data were analyzed descriptively. Results Of the 51 patients aged 19-77 years that participated in the study, 42 completed the questionnaire. All patients rated home monitoring as 'very good' or 'rather good' and were able to integrate the measuring processes into their daily routines. Overall, 93% would recommend the app and the measuring devices to their family and friends. About 60% felt that their COVID-19 treatment had benefited from home monitoring. Only few patients were unsettled by the app and use of the measuring devices. During the course of the study, the implementation process was optimized. Conclusions The use of remote monitoring in COVID-19 patients is feasible and was evaluated positively by most study patients. However, it is difficult to imagine how general practices could cope with monitoring patients with acute diseases without any further organizational support. Future research should address cost-effectiveness and changes in such clinical outcomes as hospitalization and mortality.


Assuntos
Doença Aguda , COVID-19
19.
medrxiv; 2024.
Preprint em Inglês | medRxiv | ID: ppzbmed-10.1101.2024.02.27.24303438

RESUMO

Background: Although many studies published so far on COVID-19 have examined its clinical prognosis, there is still no universal laboratory test that can assess the risk of a fatal outcome in patients with coexisting neurological diseases. Methods: The plasma concentrations of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, interleukin 6 (IL-6), D-dimers, and highly sensitive troponin I (hsTnI) were determined in a group of 400 consecutive in-patients with COVID-19 and concomitant neurological comorbidities. Results: The median concentration levels of most of the inflammatory mediators/indicators, calculated for the whole group of patients, remained above the normal reference ranges, whereas the median concentrations of these substances were much higher in the sub-group of patients who died. Backward stepwise logistic regression confirmed the statistically significant predictors of death in a descending order of odds ratios as follows: LDH (3.8), ferritin (2.8), hsTnI (2.0), IL-6 (1.7), and age (1.01). A concentration of hsTnI > 64 ng/L appeared to constitute a strong predictor of an unfavorable prognosis. Patients who were treated with lopinavir and ritonavir, who required mechanical ventilation, and treatment with dexamethasone presented with significant increase in the concentrations of all the studied inflammatory proteins and increased odds ratio for death. Conclusion: High plasma concentrations of pro-inflammatory proteins in patients suffering from COVID-19 and concomitant neurological diseases were associated with a more serious clinical course and an increased risk of death. The presence of these substances is worth monitoring as a valuable indicator of the current clinical condition of COVID-19 patients.


Assuntos
Morte , COVID-19 , Transtornos Heredodegenerativos do Sistema Nervoso
20.
medrxiv; 2024.
Preprint em Inglês | medRxiv | ID: ppzbmed-10.1101.2024.02.28.24303518

RESUMO

The COVID-19 pandemic has flooded open databases with population-level data. However, individual-level structured data, such as the course of disease and contact tracing information, is almost non-existent in open databases. Publish a structured and cleaned COVID-19 dataset with the course of disease and contact tracing information for easy benchmarking of COVID-19 models. We gathered data from Taiwanese open databases and daily news reports. The outcome is a structured quantitative dataset encompassing the course of the disease of Taiwanese individuals, alongside their contact tracing information. Our dataset comprises 579 confirmed cases covering the period from January 21, to November 9, 2020, when the original SARS-CoV-2 virus was most prevalent in Taiwan. The data include features such as travel history, age, gender, symptoms, contact types between cases, date of symptoms onset, confirmed, critically ill, recovered, and dead. We also include the daily summary data at population-level from January 21, 2020, to May 23, 2022. Our data can help enhance epidemiological modelling.


Assuntos
COVID-19
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