WWIEM's researchers have been at the heart of the UK's strategy to combat COVID-19. Our research teams have leveraged their internationally-recognized expertise in viral infections, diagnosis of infections, and clinical trials to lead the UK's research response to the greatest threat to human health in a generation.
UKRI funded: Ultan Power and Ken Mills
Professor Ultan Power and Professor Ken Mills (PGJCCR) will test a library of approximately 1000 drugs on cells in the laboratory to determine if any can reduce the toxic effects of novel coronavirus infection. The drugs are already approved for use in humans. They will be tested on airway epithelial cells grown in the lab and infected with novel coronavirus to determine if the drugs can reduce virus infection or replication and virus induced inflammatory responses. This could identify promising drugs for further testing and clinical trials.
BBSRC funded: Jose Bengoechea
Clinical studies have reported co-infections in at least 20% of COVID-19 patients. This figure is likely underestimated because ICU mechanical ventilation results in up to 75% of patients developing nosocomial pneumonia. Moreover, pathological analysis of post-mortem biopsies of lung from patients who died of severe COVID-19 revealed histopathologic findings consistent with superimposed bacterial pneumonia in some patients. Alarmingly, this occurs in a scenario of a limited arsenal of antibiotics to target these infections. Nothing is known on the effect of co-infections in SARS-CoV-2-induced pathophysiology. It is also unknown whether SARS-CoV-2 infection may affect the pathophysiology of nosocomial infections. Addressing this knowledge gap is critical if we are to develop therapeutics; otherwise, treatments may tip the balance from one infection to the other.
This happens in a scenario of a limited arsenal of antibiotics to target nosocomial infections. We will investigate the interface between SARS-CoV-2 and bacterial infections (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus) by exploiting relevant translational research models: well-differentiated primary human airway epithelial cell cultures (WD-PAECs), excellent surrogates of human airway epithelium in vivo, and PBMCs, reflecting the complexity of the human immune system. Single-cell RNA seq and multiplexed single-cell mass cytometry (CyTOF) will reveal cell-type specific immune pathways associated with the infections. These responses might be suitable for therapeutic manipulation. Cytopathogenesis, viral and bacterial replication in co-infection, and cytokines/chemokines will be additional read-outs. The effect of SARS-CoV-2 and bacteria on each other's virulence will be analysed by determining the transcriptome of exposed bacteria, and investigating viral and bacterial infection parameters upon infection of WD-PAECs and PMBCs. We will screen a panel of FDA-approved drugs affecting host-pathogen interactions to identify drugs against SARS-CoV-2 in the co-infection interface. These drugs shall be considered as new therapeutics entering clinical trials.
UK Department of Health and Social Care: David Simpson & Derek Fairley
WWIEM’s ProfessorDavid Simpson is working as part of the COVID-19 Genomics UK Consortium which has been created to deliver large scale and rapid whole genome virus sequencing to local NHS centres and the UK government. Its data will help Public Health Agencies to manage the COVID-19 outbreak and inform vaccine research efforts. Belfast is one of a network of centres throughout the UK which will sequence samples from local confirmed cases of COVID-19. The goal of the COG UK Consortium is to deliver large scale SARS CoV 2 genome sequencing capacity to hospitals, regional NHS centres and the Government that, when combined with epidemiological and clinical information, will inform interventions and policy decisions during the current UK COVID-19 epidemic. The COG-UK Consortium is an innovative partnership of NHS organisations, the four Public Health Agencies of the UK, the Wellcome Sanger Institute and more than 12 academic institutions.
EU Horizon 2020: Cliff Taggart
Professor Cliff Taggart, in partnership with HiberGene Diagnostics Ltd, Medcaptain in China, and Italian Hospital IRCCS Ospedale Policlinico San Martino, have been awarded support from EU H2020 to develop a highly accurate diagnostic test for COVID-19 that aims to show results within an hour. The test will enable clinicians to test for COVID-19 on site, eliminating the need to send tests to a centralised laboratory.
Public Health England: Thomas Waterfield & Chris Watson
Thomas Waterfield and Chris Watson are conducting a study, in collaboration with Public Health England, to investigate the seroprevalence of SARS Cov 2 antibodies in children. Four sites across the UK (Belfast, Glasgow, London and Manchester) will recruit 800 children. Immunoglobulins M and G to SARS Cov 2 will be measured at baseline, eight weeks and six months.
NIHR funded: Danny McAuley, Judy Bradley, Bronwen Connolly
This new clinical trial led by the University of Warwick seeks to find alternatives to ventilators to treat patients who are critically ill with COVID 19. The project is testing the efficacy of non-invasive interventions at an earlier stage in disease progression as an effective alternative to using ventilators for COVID-19 patients. The RECOVERY-RS Respiratory Support trial will recruit 4000 patients with the aim to find effective alternative solutions for patients with COVID-19 to reduce the need for treatment with a ventilator and to improve patient outcomes. The study is based on the theory that non-invasive interventions at an earlier stage may reduce the need for invasive ventilation with a mechanical ventilator. The trial will enable researchers to see whether any of the possible new treatments are more or less effective than those currently used for patients with COVID-19.
HSC funded: Cecilia O’Kane & Danny McAuley
As part of the UK response to the COVID-19 pandemic, the Wellcome Trust-funded REALIST clinical trial is assessing a novel allogeneic stromal cell therapy in a Phase 2 trial targeting Acute Respiratory Distress Syndrome (ARDS) caused by COVID 19. Recent reports indicate that 80-90% of COVID-19-related deaths are caused by ARDS and ICU patients with moderate-severe ARDS caused by COVID-19 have a 28 day mortality rate of ~50%. There are currently a significant number of vaccines and therapies in development for targeting the SARS CoV 2 infection. All of these treatments are targeting the virus and its ability to infect and replicate within the body, however, few therapies are in development to address ARDS. REALIST is a 1 1 randomised, Phase 2 placebo controlled, double blind study assessing the ORBCEL C stromal cell immunotherapy in 60 patients with moderate severe ARDS caused by COVD-19.
The recruitment to the REALIST- COVID-19 cohort was completed ahead of schedule and it was the first phase 2 trial in the UK of cell therapy for patients with COVID-19 to complete.
Patients in the trial are treated with a purified population of MSCs derived from umbilical cord tissue called ORBCEL-C. The ORBCEL-C therapeutic is manufactured under licence by the UK NHS Blood and Transplant Service for the REALIST COVID-19 trial.
The Novavax trial, led in Northern Ireland by Professor Danny McAuley and Professor Judy Bradley, completed recruitment of 15,000 participants throughout the UK and Northern Ireland recruited almost 500. The National Institute for Health Research (NIHR)-supported Novavax Phase 3 COVID-19 vaccine trial has achieved its recruitment target of 15,203 volunteers just two months after opening in the UK – including 482 participants from Northern Ireland. This is the first COVID-19 vaccine trial to take place in Northern Ireland and the number recruited surpassed the original target of 350.
A combined COVID-19 and flu molecular diagnostic test has been launched, as a result of the EU Horizon2020-funded project “Development and validation of rapid molecular diagnostic test for nCoV19“. Professor Cliff Taggart is a partner in the consortium led by the Irish company HiberGene. The combined COVID-19 and Flu molecular diagnostic test allows health officials to test for both illnesses using a single swab. Up to four samples can now be tested in parallel for Flu A, Flu B and COVID-19 in 60 minutes on a single HG Swift Plus unit. The HiberGene COVID-19 test development is supported by a grant of €930,000 from Horizon 2020, the EU programme for support to research and innovation. The combined test is currently undergoing the CE marking process.
Genetic mechanisms of critical illness in COVID-19
The paper reports the results of a genome-wide association study (GWAS) in 2244 critically-ill COVID-19 patients from 208 UK intensive care units (ICUs), representing >95% of all ICU beds; The study was conducted within the global collaborative study to understand the genetic basis of critical illness GenOMICC (Genetics Of Mortality In Critical Care). Since susceptibility to life-threatening infections and immune-mediated diseases are both strongly heritable traits, the authors reasoned that host genetic variation may identify mechanistic targets for therapeutic development in COVID-19. Ancestry-matched controls were drawn from the UK Biobank population study and results were confirmed in GWAS comparisons with two other population control groups: the 100,000 genomes project and Generation Scotland. They identify and replicate three novel genome-wide significant associations.Read on the Nature website
Kinetics and seroprevalence of SARS-CoV-2 antibodies in children: Tom Waterfield, Chris Watson
This paper reports the results of the second round of antibody testing in children from a prospective multicentre cohort study in the UK. Recruitment took place in April 2020, at five UK sites (Belfast, Cardiff, Glasgow, London, and Manchester) and included healthy children aged 2–15 years. Follow-up visits at all five UK sites took place between June and August 2020. The results indicate that antibody titres in children exposed to SARS-CoV-2 remain at a detectable level for at least 62 days, and that in this cohort mean antibody titres increased over time. This finding is consistent with available data on antibody titres in adults.Read on the Lancet website
SARS‐CoV‐2, bacterial co‐infections, and AMR: the deadly trio in COVID‐19?
This paper highlights how SARS-CoV-2 and bacteria in the lungs may affect each others ability to cause damage, and with the immune response to the virus being different when bacteria are present, the severity of COVID-19 in a patient could increase and the clinical outcome deteriorate. The paper also suggests the likeliness of the gut microbiota being disrupted in severe COVID-19 patients, which may affect disease outcomes, including predisposition to secondary bacterial infections of the lung.Read on EMBO website