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- W3109410882 abstract "The role of vascular occlusion in the morbidities, pulmonary and systemic, of COVID-19 has received increasing focus. Histological studies of lung tissue from COVID-19 patients have found extensively damaged endothelium of capillaries adjoining relatively intact alveoli, corresponding to hypoxemia accompanying normal breathing mechanics in such patients. Advanced image analysis of lung CT scans of COVID-19 patients reveals redistribution of blood flow from smaller to larger diameter blood vessels, this effect correlated with the degree of breathing dysfunction.Essential to the study of vascular occlusion in COVID-19 are viral properties dating back to studies of Jonas Salk in the 1940s that have been positively established for SARS-CoV-2. First, SARS-CoV-2 binds to red blood cells (RBCs), in vitro and also clinically in COVID-19 patients. Second, although fusion and replication of SARS-CoV-2 occur via ACE2, such hemagglutinating viruses initially attach to infective targets and clump with blood cells via much more abundantly distributed sialic acid (SA) glycoconjugate binding sites. SARS-CoV-2, in particular, attaches to these SA sites. Third, certain enveloped viruses express an enzyme, hemagglutinin esterase (HE), that counteracts viral-RBC clumping. Notably, among betacoronaviruses, the common cold strains express HE while SARS-CoV-2, SARS-CoV-1 and MERS, the virulent strains, do not.These hemagglutinating properties of SARS-COV-2 establish a framework for “catch and clump” induction of microvascular occlusion proposed here. Ultramicroscopic studies of tissues from COVID-19 patients indicate a key role for hemagglutination early and mid-course in COVID-19, before such clumps harden into clots via the coagulation cascade. Hemagglutination may be reversed by two anti-COVID-19 therapeutics that each competitively bind to SARS-CoV-2 spike protein, blocking such viral attachments. One therapeutic is antiviral antibodies generated by vaccines, the anti-hemagglutination effect of which is exhibited in Jonas Salk’s hemagglutination inhibition assay. The other therapeutic is ivermectin (IVM), a drug of Nobel Prize honored distinction, distributed in 3.7 billion doses worldwide. In ten clinical trials, three with randomized controls, IVM yielded mortality reductions for COVID-19 of 90% at highest doses. IVM may limit virulence of SARS-CoV-2 by steric interference with multivalent spike protein attachments to SA binding sites, blocking hemagglutination, an effect likely to target mutant viral strains." @default.
- W3109410882 created "2020-12-07" @default.
- W3109410882 creator A5058978480 @default.
- W3109410882 date "2020-01-01" @default.
- W3109410882 modified "2023-10-13" @default.
- W3109410882 title "From Cold to Killer: How SARS-CoV-2 Evolved without Hemagglutinin Esterase to Agglutinate, Then Clot Blood Cells in Pulmonary and Systemic Microvasculature" @default.
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