Long COVID and the role of fibrin amyloid (fibrinaloid) microclots

Together with Professor Resia Pretorius, we have been studying the role of fibrin amyloid microclots in the phenomena of Long COVID (and related post-infection diseases). All of the papers are on the group’s Publications page. Following considerable earlier work using electron microscopy (that uncovered ‘dense matted deposits’), we discovered the ability of tiny amounts (1 molecule per 100,000,000 fibrinogen molecules) of bacterial lipopolysaccharide to cause blood to clot into an anomalous ‘amyloid’ type form that could simply be stained with fluorogenic dyes such as thioflavin T. Similar phenomena can be observed in the blood of individuals with various chronic, inflammatory diseases such as Alzheimer’s, Parkinson’s, type 2 diabetes, and rheumatoid arthritis. These kind of fibrinaloid microclots are significantly more resistant to breakdown than are normal clots, so D-dimer measurements do not alone detect their presence, and the phenomena bear similarities to other more classical ‘amyloidoses’ and especially to the properties of prions.

It was clear early on (see also a video by Drs Jaco Laubscher & Johan Lourens) that COVID-19 was essentially a coagulopathy. We discovered extensive amyloid blood clots in ‘unclotted’ plasma of acute COVID patients, that these could be induced in ‘normal’ blood from uninfected controls by the addition of SARS-CoV-2 spike protein, and that this amyloidogenesis was also true for the plasma of individuals with Post-Acute Sequelae of COVID-19 (PASC, i.e. Long COVID).

This led to the view that careful assessment and prevention of clotting could be of clinical value in both acute and Long COVID. The latter study showed the presence of fibrinaloids in all individuals with long COVID (70/70 tested), and provided some encouraging preliminary results from clinical practice using a treatment based around anticoagulants and platelet inhibitors. Note that this was not a clinical trial; there were no controls. We do stress additionally, however, that anyone contemplating medication  for Long COVID or anything else MUST do so ONLY with the cooperation and involvement of their physicians. In particular we note the importance of assessing potential coagulation status before and during any therapy using thromboelastography.

Our present thinking is that these hard-to-remove microclots, that can inhibit blood flow to capillaries and hence O2 transfer to tissues, are involved in, and can account for, most (if not all) of the symptoms of Long COVID, and we are presently working hard to improve both the diagnostics and (with clinical colleagues) the therapeutics based on this thinking.

Mostly UK-based links: Long COVID prevalence in the UK. Funding portals such as COVID-CIRCLE. The APPG on coronavirus and how to submit evidence to it. POST report on LC.

Some useful resources for microclots and Long COVID: video interview between Dr Amy Proal & Prof Resia Pretorius; BBC discussion of Dr Beate Jaeger’s HELP apheresis; Long COVID Foundation video with Dr Marek Fabrowski on his treatment including HELP apheresis; an op-ed in The Guardian; an excellent talk by Dr  Proal on the causes of Long COVID;

My own twitter feeds and those of Prof Resia Pretorius, Dr Amy Proal, Dr Anna Brooks, The Apheresis Association, Dr Asad KhanBody Politic, Dr Jennifer Curtin, Long Covid Advocacy, Long Covid France, Long Covid Kids, Long Covid News, Long Covid Scotland. Some twitter feeds with hashtags such as Long COVID, pwLC, pwME, TeamClots, Treat Long Covid.

Other web links: Doctors with ME. LongCovid.org.