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 (including many on iron dysregulation and the role of infections) are on the group’s Publications page. Following considerable earlier work using electron microscopy (that uncovered ‘dense matted deposits’, that are equivalent), 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’ (which are different in that they are not normally detected in blood and do not involve fibrinogen), and especially in some aspects around cross-reactivity to the properties of prions. More specifically, although it was once believed that proteins whose amino acid sequence was sufficient to determine their 3D conformations always folded into their state of lowest free energy, this was always an assumption as there were far too many possibilities for it to be calculated. It turns out that more stable states (of the identical, unchanged amino acid sequence but of lower free energy) do in fact exist, that these can be formed in some circumstances, and that they typically contain ‘cross-beta’ structures that are referred to as amyloid structures. We consider that this is highly pertinent to the mechanisms and causes of long COVID. (Similar findings pertain in Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS).)
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