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.”
This time we will be getting to know Dr Maria Kaisar who is a scientist leading valuable research to identify biomarkers to better assess the quality of deceased donor organs. She explained that biomarkers can be proteins or genes that can be measured during organ donation to indicate the risk of poor function or even failure after transplantation. Her work also investigates biological processes that may be altered during organ donation and impact on effective organ function. She says that the more that can be learned about the changes in biological mechanisms, the closer we come to designing new therapies to repair organs and make transplants last longer.
Dr Kaisar says she feels privileged to have been part of the QUOD team since its creation in 2012. She recalls the strong collaborative spirit of the clinical teams (NORs, SNODs), academic partners and scientists across a host of institutions including NHSBT and transplant centres who all contributed to the development of the QUOD project. She has watched QUOD evolve into the platform it has become today and takes great pleasure in seeing QUOD samples supporting so much exciting research both nationally and internationally.
Maria has also been working on the COMPARE Trial that showed that the addition of oxygen during hypothermic machine perfusion of older DCD kidneys improved transplant outcomes. COMPARE is a component of the Consortium for Organ Preservation in Europe (COPE).
Every day is different for Maria as she spends her time in meetings, designing new experiments, analysing data and drafting grant applications and papers. She splits her time between her lab at the NHSBT Filton Blood Centre in Bristol, where she has built a small team, and at the University of Oxford working alongside colleagues in the QUOD/Ploeg Research lab at the Oxford Blood Centre. She also holds responsibilities as Vice-Chair of ESOT’s (European Society of Transplantation) Basic Science committee. Working with colleagues from across the United Kingdom and further afield in the Netherlands, Austria, Denmark, France and Belgium has provided valuable friendships that extend beyond scientific interest.
Maria is a passionate advocate of the Women in Science initiative and diversity in science. She says ‘We must rethink scientific careers to support career progression of scientists to senior leadership roles whilst caring for families – COVID has taught us that we can be productive in many ways and incorporate flexibility achieving a healthy work life balance. We also should aim to be more ethnically diverse as we can only gain valuable insights and perspectives’. The most significant obstacle faced by scientists today, she says, is the lack of long term, secure funding. COVID has shown that investment in science is essential to meet the changing medical challenges we are faced with.
Dr Kaisar’s journey in science began with her interest in biology at school, though she was also keen on philosophy, ‘very Greek!’ she laughs. With a BSc in Chemistry from the University of Athens, she took up a one-year internship that became a six-year research role at Imperial College School of Medicine. After taking some time out to start a family, she returned to work for NHSBT and developed a strong interest in organ transplantation that led to joining Professor Ploeg’s group and completing a DPhil at the University of Oxford.
When Maria isn’t pondering science she loves holidays with her family, picnics, long walks and cooking. She also loves live music and going to concerts and gigs which she hope to be able to do again soon.