A team from NDORMS has been researching the safety profile of hydroxychloroquine, either alone or in combination with azithromycin, after the drugs were suggested to be an effective treatment for COVID-19.
The NDORMS team, including Prof Dani Prieto-Alhambra and Jenny Lane, joined with over 300 international researchers from the Observational Health Data Sciences and Informatics (OHDSI) community during a four day study-a-thon to explore multiple areas around the coronavirus.
Looking at data from almost 1 million patients in six countries the team wanted to find out what side effects people who have taken hydroxychloroquine have had in the past. They found it to be safe for short-term use. However, when used in combination with azithromycin, the risk of cardiovascular death more than doubled, as reported in Science.
"We lack data on the safety of hydroxychloroquine when used at higher doses, and it is too early to be able to understand its clinical effectiveness to treat COVID-19," said Dani. "We'll conduct a new study amongst COVID-19 patients when data starts accumulating."
A pre-print (not yet peer reviewed) of these findings is now available from MedRXiv.
Researchers across Oxford's Medical Sciences Division are working tremendously hard to understand the host response to SARS-CoV2 infection. This coordinated effort involves developing serological assays, deep phenotyping the inflammatory response, and defining the role of virus-specific T cells during infection.
Kennedy researchers are contributing on a number of fronts. Prof Lynn Dustin and Dr Stephen Laidlaw are collaborating with investigators in the Nuffield Department of Medicine (NDM), Paediatrics, the Jenner, and Statistics to analyse antibodies in patients recovering from COVID-19, as well as in subjects enrolled in vaccine trials, to better understand immune protection against the virus.
Profs Fiona Powrie, Claudia Monaco and Irina Udalova lead work to understand how activation of particular white blood cells, termed innate immune cells, contribute to severe Covid-19 disease. Together with Profs Katja Simon, Mark Coles and Dr Stephen Sansom at the Kennedy, they are drawing on their expertise in myeloid cells and immunophenotyping protocols, as part of a collaboration with researchers in the Translational Gastroenterology Unit, MRC Weatherall Institute of Molecular Medicine and NDM. Their aim is to understand what drives lung inflammation in COVID-19 patients with severe disease, and to examine the interaction between inflammation and enhanced blood clotting observed in some patients.
It is truly inspiring to see how colleagues from across the Medical Sciences Division, many of whom are also working in the clinic, have come together with a sense of urgency to develop a consolidated approach for tackling key questions on how our immune system responds to the virus.
- Professor Fiona Powrie
Dr Brian Marsden, who heads the IT and Informatics Group at the Kennedy Institute, is also contributing to the COVID-19 response, leading on data management for tracking patient samples, as well as data-warehousing solutions that bring together clinical and molecular datasets and support data sharing across institutes.
Professor Fiona Powrie said: "It is truly inspiring to see how colleagues from across the Medical Sciences Division, many of whom are also working in the clinic, have come together with a sense of urgency to develop a consolidated approach for tackling key questions on how our immune system responds to the virus. In collaboration with our haematology colleagues, we hope our own work will provide important insights into the role of inflammation in thrombosis and vascular damage in severe forms of disease. We hope this mechanistic insight will inform new strategies to treat this disease."
Professor Gary Collins was part of an international team that examined models that aimed to predict either the presence of existing COVID-19 infection, future complications, or models to identify individuals at high risk for COVID-19 in the general population.
The speed of the pandemic means there is limited data available, but the review of existing published and pre-print reports led the team to declare most of them poorly reported, at high risk of bias, and included recommendations that were questionable should they be put into practice.
Published in the BMJ, the review focused on 27 studies that described 31 prediction models. They found the quality of reporting in the studies varied substantially and a description of the study population and intended use of the models was absent in almost all reports, with calibration of predictions rarely being assessed.
With many hard medical decisions associated with the spread of the COVID-19 virus being based on existing research. Gary cautioned: "Their reported performance is likely optimistic and using them to support medical decision making is not advised."
Adding to the emerging literature suggesting that the rush to conduct research for COVID-19 may come at the expense of research quality, James Smith and Andrew Carr have looked at emerging clinical trial registrations for mesenchymal stem cells (MSCs) to treat COVID-19.
The aim of the study was to explore whether or not these trial registrations are likely to produce reliable information that helps determine whether or not MSCs are useful for the treatment of the coronavirus.
They found that many studies are unlikely to produce useful information, and that there was a lack of standardisation across them to allow their information to be combined at a later date. The conduct of many trials in parallel leads to a high chance of false positives, and many of the studies are lacking in key quality indicators.
A pre-print of the study in MetaArXiv (not yet peer reviewed) features recommendations about how this situation might be improved.
The COVID Clinical Trial Planning Group, is a multidisciplinary team of experts from Oxford in immunology, infectious disease, respiratory, clinical pharmacology, and intensive care.
Led by Professor Duncan Richards, the group has rapidly come together to develop a strategy for clinical studies for non-vaccine based treatment therapies for COVID-19. They have reviewed over 30 proposals for clinical studies to date and prioritised a number, ensuring that trials don't try to recruit the same patient.
"In an emergency you need coordination. What Oxford has done is really get behind nationally prioritised work, but also to organise ourselves locally, working collaboratively with the right people in the University to really deliver something important."
- Duncan Richards
The trials include: the COPCOV study led by Nick White in Thailand, supported by the Diabetes Trial Unit, which is a very large international trial in healthcare workers looking at prophylaxis; the Principle Trial which aims to find out whether selected treatments given to people at higher risk of becoming more ill when they are infected with COVID-19 can help reduce the need for hospitalisation and the length of stay required; and the major national multi-centre clinical trial, Recovery, to test the effects of potential drug treatments for patients admitted to hospital with COVID-19. More are being recruited to or are under consideration.
"In an emergency you need coordination," said Duncan. "What Oxford has done is really get behind nationally prioritised work, but also to organise ourselves locally, working collaboratively with the right people in the University to really deliver something important."
A group of post-docs and DPhil students from Kennedy Institute of Rheumatology Journal Club, together with other departments in the Medical Sciences Division, are helping forefront COVID research groups in Oxford, the UK and around the world by vetting and digesting the vast amount of pre-prints and publications on COVID19 with an emphasis on Immunology. The idea of the initiative is to review pre-prints and papers in order to point them towards papers of relevance and good quality research.
To date 64 papers have been reviewed with the full digest available here: https://www.immunology.ox.ac.uk/covid-19/literature-digest
As the pandemic started to take hold in the UK, and with many patients hospitalised needing mechanical ventilation, it became clear there was a shortage of ventilators across the world.
NDORMS DPhil student Rob Staruch worked with his supervisor Professor Mark Thompson to build an interdisciplinary team of engineers, anaesthetists and surgeons from the University of Oxford and King's College London who started to work together to build and test a prototype ventilator called OxVent. They had a working prototype ready to present to the Cabinet Office within a week.
The OxVent is an incredibly simple device based on an Ambu (artificial manual breathing unit) bag which has been built with readily available off-the-shelf components. Most importantly, it has been designed to be produced at a large scale in a relatively short period of time and at very low cost.
The team is collaborating with Smith+Nephew to move forwards with manufacturing the ventilator and are continuing to work towards MHRA approval.
Find out more on the project website.
Martin Holt and Alice Harin are part of an Oxford-based collective using 3D printers to make PPE visors for local medics, to protect them as they help treat COVID-19 patients. Using a Danish government approved design that is suitable for higher risk medical roles, they have provided over 1000 masks to date, and all are being made available for the NHS, GP surgeries, and care homes free of charge. A fundraising campaign to cover material costs was launched and raised over £2000 in its first few days.
In Zimbabwe, a new children's orthopaedic hospital has turned tailor to use surplus theatre drapes to provide PPE protection to neighbouring doctors treating COVID patients. Chris Lavy and the NDORMS global surgery group has been partnering with the Zimbabwean Ministry of Health to build the yet opened hospital. Having an excess of old waterproof theatre drapes, the team had the idea of using them to make gowns, hats and masks.