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1.
PLoS One ; 16(5): e0251410, 2021.
Article in English | MEDLINE | ID: covidwho-1604261

ABSTRACT

The objective of this study was to explore the impact of the coronavirus disease 2019 epidemic on ongoing and upcoming drug clinical trials. Qualitative semi-structured interviews were conducted with clinical trial staff and clinical trial subjects were surveyed by questionnaire in this study. The results of interviews and questionnaire showed that coronavirus disease 2019 pandemic has led to many changes in the implementation of drug clinical trials, including: a variety of meetings being held online webinars using various platforms, telemedicine and follow-up by video, A large number of deviations from protocol and losses of follow-up, delivery of clinical trial drugs by express, additional workload caused by screening for coronavirus, and anxiety of subjects. These results suggest that the coronavirus disease 2019 outbreak has hindered the progress and damaged the quality of clinical trials. The online meeting, remote follow-up, express delivery of drugs and remote monitoring in the epidemic environment can ensure the progress of clinical trials to a certain extent, but they cannot fully guarantee the quality as before.


Subject(s)
COVID-19/pathology , Clinical Trials as Topic , Adult , Antiviral Agents/therapeutic use , Anxiety/etiology , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/virology , Humans , Interviews as Topic , Middle Aged , Pandemics , Patients/psychology , Research Personnel/psychology , SARS-CoV-2/isolation & purification , Surveys and Questionnaires , Telemedicine , Young Adult
2.
AAPS J ; 24(1): 19, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1605878

ABSTRACT

Over the past decade, artificial intelligence (AI) and machine learning (ML) have become the breakthrough technology most anticipated to have a transformative effect on pharmaceutical research and development (R&D). This is partially driven by revolutionary advances in computational technology and the parallel dissipation of previous constraints to the collection/processing of large volumes of data. Meanwhile, the cost of bringing new drugs to market and to patients has become prohibitively expensive. Recognizing these headwinds, AI/ML techniques are appealing to the pharmaceutical industry due to their automated nature, predictive capabilities, and the consequent expected increase in efficiency. ML approaches have been used in drug discovery over the past 15-20 years with increasing sophistication. The most recent aspect of drug development where positive disruption from AI/ML is starting to occur, is in clinical trial design, conduct, and analysis. The COVID-19 pandemic may further accelerate utilization of AI/ML in clinical trials due to an increased reliance on digital technology in clinical trial conduct. As we move towards a world where there is a growing integration of AI/ML into R&D, it is critical to get past the related buzz-words and noise. It is equally important to recognize that the scientific method is not obsolete when making inferences about data. Doing so will help in separating hope from hype and lead to informed decision-making on the optimal use of AI/ML in drug development. This manuscript aims to demystify key concepts, present use-cases and finally offer insights and a balanced view on the optimal use of AI/ML methods in R&D.


Subject(s)
Artificial Intelligence , Clinical Trials as Topic , Computational Biology , Drug Development , Machine Learning , Pharmaceutical Research , Research Design , Animals , Artificial Intelligence/trends , Computational Biology/trends , Diffusion of Innovation , Drug Development/trends , Forecasting , Humans , Machine Learning/trends , Pharmaceutical Research/trends , Research Design/trends
4.
J Microbiol Biotechnol ; 31(12): 1601-1614, 2021 12 28.
Article in English | MEDLINE | ID: covidwho-1595833

ABSTRACT

To overcome the ongoing COVID-19 pandemic, vaccination campaigns are the highest priority of majority of countries. Limited supply and worldwide disproportionate availability issues for the approved vaccines, together with concerns about rare side-effects have recently initiated the switch to heterologous vaccination, commonly known as mixing of vaccines. The COVID-19 vaccines are highly effective in the general population. However, none of the vaccines is 100% efficacious or effective, with variants posing more challenges, resulting in breakthrough cases. This review summarizes the current knowledge of immune responses to variants of concern (VOC) and breakthrough infections. Furthermore, we discuss the scope of heterologous vaccination and future strategies to tackle the COVID-19 pandemic, including fractionation of vaccine doses and alternative route of vaccination.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunity, Heterologous , SARS-CoV-2/immunology , Vaccination/methods , Vaccination/trends , Animals , COVID-19/immunology , COVID-19 Vaccines/classification , Clinical Trials as Topic , Humans , Mice
5.
Sci Rep ; 11(1): 23921, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1585804

ABSTRACT

Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we describe and compare the nAb titers obtained in the two assays. We observe that one assay consistently yielded higher nAb titers than the other when both assays were performed on the World Health Organization's anti-SARS-CoV-2 immunoglobulin International Standard, COVID-19 convalescent sera, and mRNA-1273 vaccinee sera. To overcome the challenge this difference in readout poses in comparing/combining data from the two assays, we evaluate three calibration approaches and show that readouts from the two assays can be calibrated to a common scale. These results may aid decision-making based on data from these assays for the evaluation and licensure of new or adapted COVID-19 vaccines.


Subject(s)
Antibodies, Neutralizing/blood , COVID-19/immunology , Neutralization Tests/standards , SARS-CoV-2/immunology , /immunology , Antibodies, Viral/blood , COVID-19/blood , Clinical Decision-Making , Clinical Trials as Topic , Diagnostic Tests, Routine , Humans , Neutralization Tests/methods , World Health Organization
6.
Pharmacol Res Perspect ; 10(1): e00909, 2022 02.
Article in English | MEDLINE | ID: covidwho-1588891

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in china and has rapidly spread to many countries around the world. The effective pharmacotherapy can reduce the mortality of COVID-19. Antiviral medications are the candidate therapies for the management of COVID-19. Molnupiravir is an antiviral drug with anti-RNA polymerase activity and currently is under investigation for the treatment of patients with COVID-19. This review focuses on summarizing published literature for the mechanism of action, safety, efficacy, and clinical trials of molnupiravir in the treatment of COVID-19 patients.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Cytidine/analogs & derivatives , Hydroxylamines/therapeutic use , COVID-19/virology , Clinical Trials as Topic , Cytidine/therapeutic use , Drug Interactions , Humans , SARS-CoV-2/isolation & purification
7.
Lancet Infect Dis ; 21(11): e342-e347, 2021 11.
Article in English | MEDLINE | ID: covidwho-1561809

ABSTRACT

Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebo-controlled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resource-poor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, non-inferiority immunogenicity trials-comparing the immune response of a vaccine candidate to that of an authorised vaccine-would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Clinical Trials as Topic , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Double-Blind Method , Humans , Immunogenicity, Vaccine , Pandemics/prevention & control , SARS-CoV-2/immunology
10.
Cardiovasc Res ; 117(9): 2045-2053, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1526155

ABSTRACT

Although coronavirus disease 2019 seems to be the leading topic in research number of outstanding studies have been published in the field of aorta and peripheral vascular diseases likely affecting our clinical practice in the near future. This review article highlights key research on vascular diseases published in 2020. Some studies have shed light in the pathophysiology of aortic aneurysm and dissection suggesting a potential role for kinase inhibitors as new therapeutic options. A first proteogenomic study on fibromuscular dysplasia (FMD) revealed a promising novel disease gene and provided proof-of-concept for a protein/lipid-based FMD blood test. The role of NADPH oxidases in vascular physiology, and particularly endothelial cell differentiation, is highlighted with potential for cell therapy development. Imaging of vulnerable plaque has been an intense field of research. Features of plaque vulnerability on magnetic resonance imaging as an under-recognized cause of stroke are discussed. Major clinical trials on lower extremity peripheral artery disease have shown added benefit of dual antithrombotic (aspirin plus rivaroxaban) treatment.


Subject(s)
Aortic Diseases , Biomedical Research/trends , Peripheral Vascular Diseases , Animals , Aortic Diseases/diagnosis , Aortic Diseases/epidemiology , Aortic Diseases/genetics , Aortic Diseases/therapy , COVID-19 , Clinical Trials as Topic , Diffusion of Innovation , Humans , Peripheral Vascular Diseases/diagnosis , Peripheral Vascular Diseases/epidemiology , Peripheral Vascular Diseases/genetics , Peripheral Vascular Diseases/therapy , Prognosis
12.
Viruses ; 12(8)2020 07 27.
Article in English | MEDLINE | ID: covidwho-1512665

ABSTRACT

Acute viral bronchiolitis causes significant mortality in the developing world, is the number one cause of infant hospitalisation in the developed world, and is associated with the later development of chronic lung diseases such as asthma. A vaccine against respiratory syncytial virus (RSV), the leading cause of viral bronchiolitis in infancy, remains elusive, and hence new therapeutic modalities are needed to limit disease severity. However, much remains unknown about the underlying pathogenic mechanisms. Neutrophilic inflammation is the predominant phenotype observed in infants with both mild and severe disease, however, a clear understanding of the beneficial and deleterious effects of neutrophils is lacking. In this review, we describe the multifaceted roles of neutrophils in host defence and antiviral immunity, consider their contribution to bronchiolitis pathogenesis, and discuss whether new approaches that target neutrophil effector functions will be suitable for treating severe RSV bronchiolitis.


Subject(s)
Bronchiolitis, Viral/immunology , Bronchiolitis, Viral/pathology , Immunity, Innate , Neutrophils/immunology , Respiratory Syncytial Virus Infections/pathology , Respiratory Syncytial Virus, Human/immunology , Acute Disease , Animals , Clinical Trials as Topic , Humans , Inflammation/virology , Lung/virology , Mice , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus, Human/pathogenicity
14.
Daru ; 29(2): 449-467, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1509383

ABSTRACT

OBJECTIVES: Due to the rapid spread of COVID-19 worldwide, many countries have designed clinical trials to find efficient treatments. We aimed to critically report the characteristics of all the registered and published randomized clinical trials (RCTs) conducted on COVID-19, and summarize the evaluation of potential therapies developed in various regions. EVIDENCE ACQUISITION: We comprehensively searched PubMed, Cochrane Library, Web of Science, Scopus, and Clinicaltrial.gov databases to retrieve all the relevant studies up to July 19, 2021, in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. We included all English-language published/registered RCTs on COVID-19, and excluded non-RCT, in-vitro/in-vivo, editorials, and review studies. Two reviewers independently evaluated all the records, and then analyzed by using SPSS 17. RESULTS: Within 3018 included studies, 2801 (92.8%) and 217 (7.2%) were registered or published RCTs consisting of about 600 synthetic drugs. Herbal medicines have been studied in 23 trials (10.6%) among the published RCTs and in 357 registered RCTs (12.7%). Hydroxychloroquine 23 (10.6%) and convalescent plasma 194 (6.9%) alone or in combination with other agents were the most frequently used interventions in published and registered RCTs, respectively. Most published RCTs have been conducted in Western Pacific Region (WPRO) (50 trials, 23.0%) including 45 trials from China. Also, a greater proportion of registered RCTs have been conducted in the Region of the Americas (PAHO) (885 trials, 31.6%) including 596 RCTs from the United States (U.S). Globally, 283 registered trials have been conducted to assess new developed vaccines for COVID or previously established for other disorders. CONCLUSION: The present study highlighted the wide range of potential therapeutic agents in published and registered COVID-19 clinical trials across a wide range of regions. However, it is urgently required to global coordination in order to conduct more well-designed trials and progress in discovering safe and effective treatments.


Subject(s)
COVID-19/drug therapy , Publications/statistics & numerical data , Synthetic Drugs/classification , Clinical Trials as Topic , Humans , Synthetic Drugs/therapeutic use , Treatment Outcome
15.
Front Immunol ; 12: 689866, 2021.
Article in English | MEDLINE | ID: covidwho-1503883

ABSTRACT

Rapid recruitment of neutrophils to an inflamed site is one of the hallmarks of an effective host defense mechanism. The main pathway through which this happens is by the innate immune response. Neutrophils, which play an important part in innate immune defense, migrate into lungs through the modulation actions of chemokines to execute a variety of pro-inflammatory functions. Despite the importance of chemokines in host immunity, little has been discussed on their roles in host immunity. A holistic understanding of neutrophil recruitment, pattern recognition pathways, the roles of chemokines and the pathophysiological roles of neutrophils in host immunity may allow for new approaches in the treatment of infectious and inflammatory disease of the lung. Herein, this review aims at highlighting some of the developments in lung neutrophil-immunity by focusing on the functions and roles of CXC/CC chemokines and pattern recognition receptors in neutrophil immunity during pulmonary inflammations. The pathophysiological roles of neutrophils in COVID-19 and thromboembolism have also been summarized. We finally summarized various neutrophil biomarkers that can be utilized as prognostic molecules in pulmonary inflammations and discussed various neutrophil-targeted therapies for neutrophil-driven pulmonary inflammatory diseases.


Subject(s)
Immunity, Innate/immunology , Neutrophils/immunology , Pneumonia/immunology , Biomarkers/blood , COVID-19/immunology , Cell Degranulation/immunology , Chemokines/immunology , Clinical Trials as Topic , Extracellular Traps/immunology , Humans , Integrins/immunology , Lung/immunology , Lung/pathology , Neutrophils/drug effects , Pneumonia/diagnosis , Pneumonia/drug therapy , Receptors, Pattern Recognition/immunology , Respiratory Burst/immunology , SARS-CoV-2 , Thromboembolism/immunology
17.
Front Biosci (Landmark Ed) ; 26(10): 948-961, 2021 10 30.
Article in English | MEDLINE | ID: covidwho-1498509

ABSTRACT

Background: Corona Virus Disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary pathogenesis is over-activation of the immune system. SARS-CoV-2 continues to mutate and spread rapidly and no effective treatment options are yet available. Mesenchymal stem cells (MSCs) are known to induce anti-inflammatory macrophages, regulatory T cells and dendritic cells. There are a rapidly increasing number of clinical investigations of cell-based therapy approaches for COVID-19. Objective: To summarize the pathogenic mechanism of SARS-CoV-2, and systematically formulated the immunomodulation of COVID-19 by MSCs and their exosomes, as well as research progress. Method: Searching PubMed, clinicaltrials.gov and Chictr.cn for eligible studies to be published or registered by May 2021. Main keywords and search strategies were as follows: ((Mesenchymal stem cells) OR (MSCs)) AND (COVID-19). Results: MSCs regulate the immune system to prevent cytokine release syndrome (CRS) and to promote endogenous repair by releasing various paracrine factors and exosomes. Conclusions: MSC therapy is thus a promising candidate for COVID-19.


Subject(s)
COVID-19/therapy , Exosomes/transplantation , Immunomodulation/immunology , Lung Injury/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/metabolism , COVID-19/epidemiology , COVID-19/virology , Clinical Trials as Topic , Exosomes/immunology , Exosomes/metabolism , Humans , Lung Injury/physiopathology , Lung Injury/virology , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/immunology , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Pandemics , Regeneration/immunology , Regeneration/physiology , SARS-CoV-2/immunology , SARS-CoV-2/physiology
19.
PLoS One ; 16(10): e0256839, 2021.
Article in English | MEDLINE | ID: covidwho-1496495

ABSTRACT

INTRODUCTION: Infective endocarditis (IE) is a severe and highly prevalent infection among people who inject drugs (PWID). While short-term (30-day) outcomes are similar between PWID and non-PWID, the long-term outcomes among PWID after IE are poor, with 1-year mortality rates in excess of 25%. Novel clinical interventions are needed to address the unique needs of PWID with IE, including increasing access to substance use treatment and addressing structural barriers and social determinants of health. METHODS AND ANALYSIS: PWID with IE will be connected to a multidisciplinary team that will transition with them from hospital to the community. The six components of the Second Heart Team are: (1) peer support worker with lived experience, (2) systems navigator, (3) addiction medicine physician, (4) primary care physician, (5) infectious diseases specialist, (6) cardiovascular surgeon. A convergent mixed-methods study design will be used to test the feasibility of this intervention. We will concurrently collect quantitative and qualitative data and 'mix' at the interpretation stage of the study to answer our research questions. ETHICS AND DISSEMINATION: This study has been approved by the Hamilton Integrated Research Ethics Board (Project No. 7012). Results will be presented at national and international conferences and submitted for publication in a scientific journal. CLINICAL TRAIL REGISTRARION: Trial registration number: ISRCTN14968657 https://www.isrctn.com/ISRCTN14968657.


Subject(s)
Endocarditis/complications , Substance Abuse, Intravenous/complications , Clinical Trials as Topic , Disease Management , Endocarditis/therapy , Feasibility Studies , Humans , Patient Care Team , Patient Selection , Substance Abuse, Intravenous/therapy
20.
Br J Clin Pharmacol ; 87(9): 3408-3424, 2021 09.
Article in English | MEDLINE | ID: covidwho-1494605

ABSTRACT

SARS-CoV-2 is the novel coronavirus behind the COVID-19 pandemic. Since its emergence, the global scientific community has mobilized to study this virus, and an overwhelming effort to identify COVID-19 treatments is currently ongoing for a variety of therapeutics and prophylactics. To better understand these efforts, we compiled a list of all COVID-19 vaccines undergoing preclinical and clinical testing using the WHO and ClinicalTrials.gov database, with details surrounding trial design and location. The most advanced vaccines are discussed in more detail, with a focus on their technology, advantages and disadvantages, as well as any available recent clinical findings. We also cover some of the primary challenges, safety concerns and public responses to COVID-19 vaccine trials, and consider what this can mean for the future. By compiling this information, we aim to facilitate a more thorough understanding of the extensive COVID-19 clinical testing vaccine landscape as it unfolds, and better highlight some of the complexities and challenges being faced by the joint effort of the scientific community in finding a prophylactic against COVID-19.


Subject(s)
COVID-19 Vaccines , COVID-19 , Clinical Trials as Topic , Humans , Pandemics , SARS-CoV-2
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