Since March 2020 the QUOD team has been supporting the national effort in the fight against COVID-19. QUOD’s extensive biobanking expertise, infrastructure and personnel have served to set up the NHSBT Oxford COVID BioArchive (COBA). Over 68,000 blood samples from convalescent plasma donors who have recovered from COVID-19 have been collected and processed as part of the NHSBT Convalescent Plasma programme. In addition, since September COBA has received over 18,000 samples collected from recipients of convalescent plasma and monoclonal antibody treatment in the international RECOVERY trial.
These samples were used by a number of research groups, NHSBT and Public Health England in a variety of projects, including assessment of novel COVID-19 tests, characterisation of COVID-19 antibody function, and analysis of the efficacy of convalescent plasma treatment. With this COVID BioArchive, we have been able to establish a robust and sustainable resource for future validation and research helping us to gain better insight into COVID-19 and anticipate targeted intervention.
You may have heard that on 15th January randomisations of patients into convalescent plasma was paused following disappointing interim results that showed no evidence that convalescent plasma has an overall benefit on patient outcomes in moderately ill people. Work to search for evidence of benefit in subgroups before organ damage and hospitalisation occurs is now under consideration.
Given the quantity of samples now available, it has been decided that collection of further plasma samples will not be resumed. The news may seem discouraging, however an important scientific question has been answered. In terms of the scale and volume of the operation this was a considerable undertaking that has proved that the QUOD infrastructure in close collaboration with the NHSBT’s Blood Service has the capacity and versatility to help and meet such an important demand.
Over 250,000 samples are currently stored in the COVID BioArchive to be used for dedicated research questions and validation of novel tests. Applications are welcome from national and international research groups or health care authorities.
This year, as has become our new norm, the BTS Congress 2021 was hosted using an online platform, allowing delegates to experience interactive plenary sessions and parallel sessions similar to when attending the conference. However unique to the online experience was the opportunity to access content ‘on-demand’, including the additional option to listen to pre-recorded abstract talks, at a time that suits you. Although, many were saddened by the lost opportunity to meet with colleagues and friends, the commitment from BTS to provide an opportunity for clinicians and researchers to gather and share their research from the last 12-months was an absolute success and credit to the organisers.
For this conference, I submitted an abstract titled ‘Brain death specific glomerular matrix degradation profiles are associated with long-term graft dysfunction in kidney transplant’ on behalf of our teams at NHSBT and the Oxford Transplant research lab in University of Oxford. This abstract was selected for presentation as part of the ‘Medawar Award Session’, where my abstract and presentation was considered for the award along with three other researchers who also submitted abstracts for basic science in transplantation. I feel incredibly fortunate to have had our abstract considered for the Medawar award, and was excited to highlight how we have utilised invaluable samples from the QUOD biobank. Our research utilised 60 kidney biopsies from the QUOD biobank from both DBD and DCD donors. Our work described a DBD specific degradation profile for cytoskeletal proteins in donor kidneys that linked to suboptimal 12month posttransplant function. Our research was considered novel in that it indicates that protein degradation may affect donor kidneys and post-transplant function. Preparing for my live presentation was also a memorable experience, involving many rehearsals with my supervisors Dr Kaisar and Prof Ploeg and colleagues, many adjustments and changes before the final live talk.
Our group also had a second opportunity to present our research work involving the analysis of QUOD samples. A second abstract titled ‘Protein profiles in deceased donor kidneys associated with 12-Month post-transplant kidney function’ was accepted as a pre-recorded talk, presented by our colleague Priyanka Joshi. This study utilised 185 kidney biopsies from the QUOD biobank for proteomic analysis, comparing DBD and DCD donors with differing functional outcomes 12mth posttransplantation. This study showed that protein markers in donor kidneys associate to posttransplant outcomes and indicate which biological pathways may play a role in determining the donor kidney quality.
Our research work has highlighted the value of the QUOD samples; based on the collection protocols, these samples provide us with confidence regarding sample quality and collection continuity. Importantly, our sample selection and analysis is linked with the clinical and demographic metadata that we receive from the National Transplant Registry from NHSBT. The combination of the selection of QUOD samples and donor and recipient metadata makes a unique research resource.
The overarching focus of the BTS congress was the impact of COVID-19 on transplantation, with NHSBT statistics team highlighting changes in trends of donation and transplantation due to the pandemic. An invited keynote speaker focused on ‘resilience’ encouraging people to reflect on their own resilience and how they have adjusted to the inevitable changes that have come along with a global pandemic, whilst looking to the future with reasonable caution but also excitement. Several talks also touched on emerging perfusion technologies and the improvements they may have on outcomes in the future, and evaluating single centre experiences.
Overall the BTS Congress 2021 was a great success despite the mammoth task of moving the conference to an online platform. The opportunity to bring together scientists and clinicians to discuss research, trends and experiences in transplantation is essential to moving the field forward. The conference provided an excellent opportunity to showcase research work, however the opportunity to interact with each other; ask questions, discuss and debate ideas was lacking and greatly missed. The representation of QUOD, NHSBT and the University of Oxford was strong, and hopefully more researchers were inspired to consider QUOD samples for their ongoing work.
Until recently, only organs removed for transplant, but subsequently not transplanted were available to researchers. Thanks to a collaboration between QUOD and Newcastle University, in partnership with NHS Blood and Transplant, new arrangements have been implemented that will allow hearts, lungs and pancreases which are unsuitable for transplantation to be retrieved for research purposes. This will greatly facilitate ongoing research into developing ways more donated organs can be converted into successful life-saving transplants.
Clare Denison, Lead Specialist – Innovation and Research ODT at NHS Blood and Transplant, said: “This is a significant moment for our organisation and researchers across the country. INOAR will change the face of transplantation and ultimately improve patient outcomes and quality of life in the future.”
This development is particularly exciting for diabetes researchers. Almost 4 million people in the UK are living with diabetes. The condition occurs when the pancreas doesn’t produce enough insulin, or when it can’t produce any at all, which leads to blood glucose levels being too high. Until now, the pancreas has not been removed, or even sampled following the death of people with diabetes during organ donation for transplantation. Research into the mechanisms preventing normal pancreatic insulin production in diabetes has therefore been limited to the small number of post-mortem samples currently stored in the UK.
Dr Elizabeth Robertson, Director of Research at Diabetes UK, said: “This is an exciting step forward that we hope will rapidly advance our understanding of the causes and progression of diabetes … world-class scientists will now have vital access to pancreatic tissue, propelling our knowledge of diabetes forward and bringing us a step closer to a world where diabetes can do no harm.”
QUOD is very pleased to collaborate with the Blood Donor Service to support two major research projects related to COVID-19.
First, QUOD is providing support for the Convalescent Plasma Trials, REMAP-CAP and RECOVERY. The trials will collect plasma samples from patients who have recovered from COVID-19 to administer to patients suffering from serious symptoms in the hope that this will boost their production of antibodies. QUOD personnel are assisting with the preparation and distribution of plasma from recovered patients, as well as the acceptance, storage, and distribution of plasma from trial participants.
In addition, assistance from QUOD was essential in the effort to rapidly scale up validation of COVID-19 antibody tests. COVID negative plasma samples from the QUOD biobank were used to provide a ‘healthy patient’ control group to test for false positives. QUOD personnel have also been hard at work preparing additional plasma samples provided by the Blood Donor Service for testing. Initial results of this antibody testing are described in this pre-print.
The swift and efficient deployment of QUOD resources and personnel to support these efforts is a strong testimony to the strategic value of the research platform we have built together. We are glad to have a meaningful role in enabling the national response to the crisis.