Increased levels of inflammatory molecules in blood of Long COVID patients point to thrombotic endotheliitis



Turner, Simone, Naidoo, Caitlin, Usher, Thomas, Kruger, Arneaux, Venter, Chantelle, Laubscher, Gert Jacobus, Khan, Asad, Kell, Douglas ORCID: 0000-0001-5838-7963 and Pretorius, Etheresia ORCID: 0000-0002-9108-2384
(2022) Increased levels of inflammatory molecules in blood of Long COVID patients point to thrombotic endotheliitis. [Preprint]

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Abstract

<h4>ABSTRACT</h4> The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, and fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations of Von Willebrand Factor, platelet factor 4,serum amyloid A, α-2antiplasmin E-selectin, and platelet endothelial cell adhesion molecule-1, in the soluble part of the blood. It was noteworthy that the mean level of α-2-antiplasmin exceeded the upper limit of the laboratory reference range in Long COVID patients, and the other 5 were significantly elevated in Long COVID patients as compared to the controls. This is alarming if we take into consideration that a significant amount of the total burden of these inflammatory molecules has previously been shown to be entrapped inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules). We also determined that by individually adding E-selectin and PECAM-1 to healthy blood, these molecules may indeed be involved in protein-protein interactions with plasma proteins (contributing to microclot formation) and platelet hyperactivation. This investigation was performed as a laboratory model investigation and the final exposure concentration of these molecules was chosen to mimic concentrations found in Long COVID. We conclude that presence of microclotting, together with relatively high levels of six inflammatory molecules known to be key drivers of endothelial and clotting pathology, points to thrombotic endotheliitis as a key pathological process in Long COVID. This has implications for the choice of appropriate therapeutic options in Long COVID. <h4>SENTENCE SUMMARY</h4> The presence of fibrinaloid microclots and multiple inflammatory molecules in the soluble part of blood points to thrombotic endotheliitis as a key pathological process in Long COVID.

Item Type: Preprint
Uncontrolled Keywords: 3207 Medical Microbiology, 32 Biomedical and Clinical Sciences, Clinical Research, Coronaviruses, Hematology, 2.1 Biological and endogenous factors, Cardiovascular
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 25 Oct 2023 09:59
Last Modified: 19 Jul 2024 10:15
DOI: 10.1101/2022.10.13.22281055
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3176427