Abstract DP367: SARS CoV-2 S1 spike protein aggravates ischemic stroke injury in C57BL/6J mice.

Introduction: Ischemic stroke is one of the potential neurological complications of COVID-19. Clinical evidence demonstrates that SARS-CoV-2 infection considerably increases stroke risk. The interplay between endothelial dysfunction, exaggerated systemic inflammation, and activation of the coagulation cascade are the key determinants of the pathology. Although direct viral neurotropism in the brain remains incompletely understood, current evidence suggests that viral proteins—such as the spike (S1) subunit cleaved by host cells proteases, may infiltrate the brain via the circulation and contribute to cerebrovascular pathology. Here, we hypothesize that the SARS-CoV-2 S1-spike protein exacerbates stroke outcomes and cerebrovascular complications in standard wild type laboratory mice Methods: 3-month-old male C57BL/J6 mice were injected with recombinant SARS-CoV-2 S1 spike protein (9ug/animal, Sino Biologicals USA) intravenously which was followed by photothrombotic stroke 7 days later. Mice were tested for motor function (rotarod and adhesive removal) and were sacrificed at 72h for stroke infarct size analysis and estimation of inflammation, blood-brain barrier (BBB) permeability, endothelial dysfunction and coagulation. Results: Rotarod and adhesive removal tests showed that spike protein administration impaired post-stroke motor function. Administration of S1 spike protein aggravated infarct volume (Fig.1), neuro inflammation and BBB permeability. Ongoing plasma analysis is expected to show that S1 spike protein induces post-stroke hypercogulation activation. Conclusion: Taken together, these data indicate that SARS-CoV-2 S1 spike protein accelerates post stroke motor dysfunction, stroke severity and hypercoagulation. Further investigation into the mechanisms of action of SARS-CoV-2 spike protein is needed to develop effective therapy for COVID-19-impacted stroke patients.