"Abstract
... A few years ago, we discovered that fibrinogen in blood can clot into an anomalous ‘amyloid’ form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies... Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored ‘triple’ anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders...
Introduction
... At present there is no established treatment for long COVID, so from a systems point of view it is important to understand which symptoms are ‘primary’, and which are simply secondary effects of the primary symptoms themselves. This would allow treatment strategies to focus on the primary symptoms and their causes. We here make the case (with evidence) that much of the aetiology of long COVID can be attributed to the formation of aberrant amyloid fibrin microclots, triggered in particular by the SARS-Cov-2 spike protein, and that by inhibiting the transport of erythrocytes to capillaries, and hence O2 transfer, it is these amyloid microclots that are mainly responsible for the various long COVID symptoms observed. The microclots may also present novel antigens that lead to the production of autoantibodies, that can exacerbate symptoms further. This understanding of the role of such microclots may be expected to lead to an effective strategy for treating long COVID (and probably for other, related conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS))...
Conclusions
In addition to microclot formation, significant platelet dysfunction and a systemic endotheliitis drive systemic cellular hypoxia. These pathologies can explain most, if not all, of the lingering symptoms to which individuals with long COVID refer."