How to spend £100m annually for five years to solve ME and Long COVID
A proposal from Douglas B. Kell and Etheresia Pretorius
Today we’re launching the ‘£100m challenge’. Over the next few months we’ll be asking researchers, and patients following the research closely, to share their ideas for how they would spend £100m annual biomedical research funding for ME and Long Covid in the UK over a five-year time horizon.
To kick us off, today Douglas B. Kell and Etheresia Pretorius share their views on where they would get started. Douglas B. Kell is Chair of Systems Biology at The University of Liverpool. Etheresia Pretorius is Distinguished Research Professor in the Physiological Sciences Department, Stellenbosch University. They have collaborated for some 13 years. You can find a summary of their work in this area here. See also #TeamClots on X/twitter.
We begin by noting that the number £100m, might in general terms be compared with the funding for cancer in the UK. The research spend each year of Cancer Research UK alone is something north of £400m for about 3 million patients. Looking for £100m annually for a disease affecting comparable millions is entirely reasonable. The economic case (multiplying a few million patients by salaries of a few tens of thousands comes to many tens of billions of pounds), aside from the human suffering, is sufficient to show that funding medical research into treatments improving quality of life sufficiently to allow people to work is a no-brainer. Not only is the amount of funding reasonable, but there are plenty of good ways to spend it. This is where we’d begin.
Centres of excellence
We advocate for the co-location of basic research and clinical studies in centres of excellence across the UK. While funding needs to be ring-fenced for both kinds of study, it is best concentrated in a few centres (perhaps 10–20). The budget should include clinicians, scientists, equipment and the technicians to run it, plus studentship programmes, online anonymised databases, and data scientists who can make use of them.
We calculate that the funding needed for one postdoc, without major overheads but including Principal Investigator costs, plus consumables, travel and some kit is around £125k a year. So, 520 postdocs (26–52 per centre) carrying out the underpinning science research, would require approximately £65 million per year, or around 65% of the total funding. The other 35% would provide the budget for clinical studies.
Underpinning science
To understand the basis of ME/CFS and Long Covid, we need more and better biomarkers (biological molecules that provide measurable signs of disease). Research in recent years, including our own, indicates clearly that persistent viral elements cause inflammation of the lining of blood vessels, which underlies many of the symptoms.1 This inflammation can lead to the production of microclots that block capillaries and can result in fatigue and other effects.
Autoantibodies are another significant feature and require detailed immunophenotyping (a way to detect and define cell proteins associated with a particular disease or diseases). We need large-scale studies for these, along with good databases. Similar phenomena are found in Long COVID,2 and the relevant centres should study both diseases (and consider expanding to other, similar diseases).
A picture of fibrinaloid microclots, whose numbers are greatly increased in ME and Long COVID.
Complex diseases such as ME/CFS and Long COVID also require systems-wide analyses. Systems biology is used to model interactions within a complex biological system such as the human body in a more holistic way. This could underpin the discovery of new biomarkers that can be used to indicate disease severity.
Identifying genes associated with the diseases can lead to the discovery of enzymes and biological processes that may be relevant to providing treatment options. Their value is massively improved by also recording data on lifestyle and behaviour influenced by the interaction of a person’s genes with their environment; we think this is an essential element for funding. There should also be no ‘left-behind’ group – it is vital to include those whose disease severity may mean that they cannot attend clinics.
The centres of excellence would need world-leading scientific instrumentation initiatives, since traditional methods have been making slow progress.
Clinical studies looking towards treatments
Rightly or wrongly, randomised controlled trials (RCTs), which include placebos, are widely seen as the gold standard for getting a new treatment ‘on the books’. (This said, there are examples of clinical practice running far ahead of RCTs, such as in the treatment of Helicobacter for ulcers.) Our own research has given us an opinion on the best targets for treatment, especially for Long COVID3 with a focus on anticoagulation in both arms of a trial (i.e. including inhibitors of platelet activation as well as anticoagulants in both the control and the study group). This should be accompanied by measurement of coagulation properties, to minimise bleeding risks.
We believe that any RCT with a scientific basis (especially viral persistence) needs to be accelerated. Testing anticoagulation and eradicating the virus are not mutually exclusive – we can provide appropriate anticoagulation with and without antivirals. We do not need to test single anticoagulants, as we already know they do not work. We believe that fibrinolytic enzymes such as nattokinase (from fermented soybeans) and serrapeptase (from silkworms) may be of value. These clinical studies should be limited to proper biomedical studies: we don’t need any more trials of CBT and behavioural treatments. The patients have waited long enough for progress on treatment.
Overall, there is a community ready and willing to deliver the research, and many new findings indicating the bases of these diseases. We think that the case for a major investment in these areas of research is clear. It simply needs to happen.
We hope this contribution from Douglas B. Kell and Etheresia Pretorius will get the conversation started. How would you spend £100m annual funding for biomedical ME and Long Covid research over a five-year time horizon? If you’re interested to contribute, let us know. We hope to run more pieces on this theme over the next few months.
See for example: Nunes, J. M., Kruger, A., Proal, A., Kell, D. B. & Pretorius, E. (2022). The Occurrence of Hyperactivated Platelets and Fibrinaloid Microclots in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Pharmaceuticals (Basel) 15, 931; Nunes, J. M., Kell, D. B. & Pretorius, E. (2023). Cardiovascular and haematological pathology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a role for Viruses. Blood Rev 60, 101075; Nunes, J. M., Kell, D. B. & Pretorius, E. (2024). Herpesvirus Infection of Endothelial Cells as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Viruses 16, 572; Arron, H. E., Marsh, B. D., Kell, D. B., Khan, M. A., Jaeger, B. R. & Pretorius, E. (2024). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease. Front Immunol 15, 1386607.
See for example: Kell, D. B., Laubscher, G. J. & Pretorius, E. (2022). A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J 479, 537-559; Kell, D. B. & Pretorius, E. (2022). The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, long COVID and ME/CFS: evidence, mechanisms, and therapeutic implications. Biochem J 479, 1653-1708; Kell, D. B. & Pretorius, E. (2023). Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases? Biochem J 480, 1217-1240.
See Footnote 2 and see also: Laubscher, G. J., Lourens, P. J., Venter, C., Kell, D. B. & Pretorius, E. (2021). TEG®, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy. J Clin Med 10, 5381; Laubscher, G. J., Khan, M. A., Venter, C., Pretorius, J. H., Kell, D. B. & Pretorius, E. (2023). Treatment of Long COVID symptoms with triple anticoagulant therapy.
Thank you for this, it’s extremely interesting and I hope someone who has leverage might read this too!
I would also like to see research exploring the overlap of ME/LC with hEDS. Often the most severe ME/LC patients have more hEDS-type symptoms as well as POTS and MCAS – all of which are features of both illnesses that correlate with severity.
Given the kallikrein genes have just been found as a possible cause for a high proportion of hEDS patients, and explain the link between all of these issues and others such as coagulation and RAAS problems, it seems urgent that this important link be studied further.
Thanks - some great ideas to get started. I especially like the idea of 10-20 centres of excellence in the UK with funding for both research and clinical work. If well publicised this would give local healthcare practitioners somewhere they can go to ask for advice, as is already available for other diseases.