Rapid Detection and Inhibition of SARS-CoV-2-Spike Mutation-Mediated Microthrombosis.

Abstract

Activation of endothelial cells following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is thought to be the primary driver for the increasingly recognized thrombotic complications in coronavirus disease 2019 patients, potentially due to the SARS-CoV-2 Spike protein binding to the human angiotensin-converting enzyme 2 (hACE2). Vaccination therapies use the same Spike sequence or protein to boost host immune response as a protective mechanism against SARS-CoV-2 infection. As a result, cases of thrombotic events are reported following vaccination. Although vaccines are generally considered safe, due to genetic heterogeneity, age, or the presence of comorbidities in the population worldwide, the prediction of severe adverse outcome in patients remains a challenge. To elucidate Spike proteins underlying patient-specific-vascular thrombosis, the human microcirculation environment is recapitulated using a novel microfluidic platform coated with human endothelial cells and exposed to patient specific whole blood. Here, the blood coagulation effect is tested after exposure to Spike protein in nanoparticles and Spike variant D614G in viral vectors and the results are corroborated using live SARS-CoV-2. Of note, two potential strategies are also examined to reduce blood clot formation, by using nanoliposome-hACE2 and anti-Interleukin (IL) 6 antibodies.

• Authors: Sandro Satta, Angela Lai, Susana Cavallero, Cayden Williamson, Justin Chen, Ana M Blázquez-Medela, Mehrdad Roustaei, Barbara J Dillon, Nureddin Ashammakhi, Dino Di Carlo, Zhaoping Li, Ren Sun, Tzung K Hsiai
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 8 Issue 23 Pg. e2103266 (12 2021) ISSN: 2198-3844 [Electronic] Germany
• PMID: 34687279 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.

Chemical References

• Antibodies
• Interleukin-6
• Liposomes
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2
• Fibrin
• ACE2 protein, human
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2 (chemistry, genetics, metabolism)
• Antibodies (chemistry, immunology, metabolism)
• Blood Coagulation (physiology)
• COVID-19 (diagnosis, virology)
• Endothelial Cells (chemistry, cytology, metabolism)
• Fibrin (chemistry, metabolism)
• Genetic Vectors (genetics, metabolism)
• Humans
• Interleukin-6 (immunology)
• Liposomes (chemistry)
• Microfluidics (methods)
• Mutation
• Nanoparticles (chemistry)
• Platelet Aggregation
• SARS-CoV-2 (isolation & purification, metabolism)
• Spike Glycoprotein, Coronavirus (analysis, genetics, metabolism)