A5004813128- COVID-19 Clinical Research Studies
- Long-Term Effects of COVID-19
- CRISPR and Genetic Engineering
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- COVID-19 and healthcare impacts
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA modifications and cancer
- Animal Genetics and Reproduction
- Respiratory Support and Mechanisms
- Global Cancer Incidence and Screening
- Lung Cancer Treatments and Mutations
- Lung Cancer Diagnosis and Treatment
- Smoking Behavior and Cessation
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Conducting polymers and applications
- Telemedicine and Telehealth Implementation
- Infectious Encephalopathies and Encephalitis
- Health and Medical Research Impacts
- COVID-19 Impact on Reproduction
- Blood properties and coagulation
- Intensive Care Unit Cognitive Disorders
- Anorectal Disease Treatments and Outcomes
- Pluripotent Stem Cells Research
University of Manchester
2020-2025
University of Leeds
2025
Salford Royal NHS Foundation Trust
2020-2024
Manchester Academic Health Science Centre
2020-2023
Institute of Immunology
2020-2021
Manchester University NHS Foundation Trust
2018-2020
University of Nebraska–Lincoln
2019
University of North Carolina at Chapel Hill
2019
Wythenshawe Hospital
2019
North Manchester General Hospital
2017
COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal profiling on both whole blood peripheral mononuclear cells (PBMCs) of hospitalized patients during peak pandemic in UK. Here, we report key signatures present shortly after hospital admission that were severity COVID-19. Immune related to shifts neutrophil T...
BackgroundEmerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these presently remains ill-defined.MethodsHere, we describe phenotypic functional characteristics of B T cells hospitalized COVID-19 during acute at 3–6 months convalescence.FindingsWe report alterations cell subsets observed were largely recovered convalescent patients. In...
Abstract Lentiviral vectors are useful experimental tools for stable gene delivery and have been used to treat human inherited genetic disorders hematologic malignancies with promising results. Because some of the lentiviral vector components cytotoxic, transient plasmid transfection has produce large batches needed clinical trials. However, this method is costly, poorly reproducible hard scale up. Here we describe a general construction packaging cell lines that continuously vectors. This...
Background COVID-19 is associated with a dysregulated immune response but it unclear how dysfunction contributes to the chronic morbidity persisting in many patients during convalescence (long COVID). Methods We assessed phenotypical and functional changes of monocytes hospitalisation up 9 months following COVID-19, respiratory syncytial virus or influenza A. Patients progressive fibrosing interstitial lung disease were included as positive control for severe, ongoing injury. Results...
ABSTRACT Gammaretroviral and lentiviral vectors are promising tools for gene therapy, but they can be oncogenic. The development of safer depends on a quantitative assay insertional mutagenesis. Here we report rapid, inexpensive, reproducible which uses murine cell line to measure the frequency interleukin-3 (IL-3)-independent mutants. Lentiviral gammaretroviral cause mutagenesis at similar frequencies; however, use different mechanisms. Human immunodeficiency virus (HIV)-based generate...
Ultra-wide range spectral ellipsometry sheds light on the anomalous optical conductivity of conducting polymers.
Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases critical coronavirus disease 2019 (COVID-19) pneumonia. The impact autoimmunity toward III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% severe disease) and 1,489 SARS-CoV-2-naive individuals. studied the prevalence capacity AABs IFNλ IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, 21) or IFNλ1–IFNλ3 as antigens,...
Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present different disease severity. Here, we determined 171 microRNAomes from 58 hospitalized (Cohort 1) of 25 in the same samples. Combining microRNA (miRNA) measurements allowed for discrimination severe cases greater accuracy than using miRNA or alone. Severity group-specific associations between miRNAs COVID-19-associated (e.g., IL6, CCL20) clinical hallmarks...
ABSTRACT Background SARS‐CoV2 infections increase the risk of ischemic stroke (IS), potentially through a thromboinflammatory cascade driven by an imbalance in ratio Von Willebrand Factor (VWF) and disintegrin metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13), leading to formation ultra‐large VWF (UL‐VWF). However, infection's contribution any VWF/ADAMTS13 axis subsequent response post‐stroke remain poorly understood. Methods We performed detailed profile plasma...
Gammaretroviral and lentiviral vectors have been used successfully in several clinical gene therapy trials, although powerful enhancer elements caused insertional mutagenesis clonal dysregulation. Self-inactivating with internal heterologous regulatory developed as potentially safer more effective alternatives. Lentiviral containing a ubiquitous chromatin opening element from the human HNRPA2B1-CBX3 locus (A2UCOE), which allows position-independent, long-term transgene expression, are...
Some gene therapy strategies are compromised by the levels of expression required for therapeutic benefit, and also breadth cell types that require correction. We designed a lentiviral vector system in which transgene is under transcriptional control short form constitutively acting elongation factor 1α promoter (EFS) combined with essential elements locus region β-globin (β-LCR). show β-LCR can upregulate EFS activity specifically erythroid cells but does not alter myeloid or lymphoid...
ABSTRACT Insertional mutagenesis by viral vectors is a problem in gene therapy. We recently reported that lentiviral with an intact HIV long terminal repeat (LTR) caused insertional activation transcripts from the 5′ LTR splicing to adjacent gene. Here we demonstrate level of transcription LTR, and also activation, dependent on internal promoter vector. show there are more originating than from, or reading through, 3′ LTR. This study will allow design safer for applications which required.
Abstract Background The pathogenesis of COVID-19, caused by a novel strain coronavirus (SARS-CoV-2), involves complex host-virus interaction and is characterised an exaggerated immune response, the specific components which are poorly understood. Here we report outcome longitudinal profiling study in hospitalised patients during peak COVID-19 pandemic UK show relationship between responses severity clinical presentation. Methods Coronavirus Immune Response Clinical Outcomes (CIRCO) was...
Background The COVID-19 pandemic has presented substantial new challenges to clinical and research teams. Our objective was analyse the experience of investigators delivery staff regarding response in order identify these as well solutions for future planning. Methods We conducted a survey diverse involved trials across UK. This delivered online centres linked NIHR Respiratory Translational Research Collaboration. Responses were analysed using formal thematic analysis approach common themes...
It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate outcomes are critical to patients and clinicians, facilitate relevance, interpretability, comparability. This methodological systematic review describes evaluated in 415 RCTs COVID-19, were registered with ClinicalTrials.gov, by 5 May 2020, instruments used measure these outcomes. Significant heterogeneity was observed selection instruments. Mortality, adverse events...
Emerging studies indicate that some COVID-19 patients suffer from persistent symptoms including breathlessness and chronic fatigue; however the long-term immune response in these presently remains ill-defined. Here we describe phenotypic functional characteristics of B T cells healthy individuals with acute or convalescent COVID-19. We report alterations cell subsets observed were largely recovered patients. In contrast, displayed persistence a cytotoxic programme evident CD8+ as well...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the clinical COVID-19 is associated with an exaggerated immune response and monocyte infiltrates lungs other peripheral tissues. It now increasingly recognised that chronic morbidity persists some patients. We recently demonstrated profound alterations of monocytes hospitalised currently unclear whether these abnormalities resolve or progress following patient discharge. show here blood convalescent...
Abstract It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate outcomes are critical to patients and clinicians, facilitate relevance, interpretability, comparability. This methodological systematic review describes evaluated in 415 RCTs COVID-19, were registered with ClinicalTrials.gov, by 5/5/2020. Significant heterogeneity was observed selection instruments used measure them. Mortality, adverse events treatment success or...