SARS-CoV-2 spike protein induces abnormal inflammatory blood clots neutralized by fibrin immunotherapy
Ryu, J. K.; Sozmen, E. G.; Dixit, K.; Montano, M.; Matsui, Y.; Liu, Y.; Helmy, E.; Deerinck, T. J.; Yan, Z.; Schuck, R.; Acevedo, R. M.; Spencer, C. M.; Thomas, R.; Pico, A. R.; Zamvil, S. S.; Lynch, K. L.; Ellisman, M. H.; Greene, W. C.; Akassoglou, K.
Show abstract
Blood clots are a central feature of coronavirus disease-2019 (COVID-19) and can culminate in pulmonary embolism, stroke, and sudden death. However, it is not known how abnormal blood clots form in COVID-19 or why they occur even in asymptomatic and convalescent patients. Here we report that the Spike protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the blood coagulation factor fibrinogen and induces structurally abnormal blood clots with heightened proinflammatory activity. SARS-CoV-2 Spike virions enhanced fibrin-mediated microglia activation and induced fibrinogen-dependent lung pathology. COVID-19 patients had fibrin autoantibodies that persisted long after acute infection. Monoclonal antibody 5B8, targeting the cryptic inflammatory fibrin epitope, inhibited thromboinflammation. Our results reveal a procoagulant role for the SARS-CoV-2 Spike and propose fibrin-targeting interventions as a treatment for thromboinflammation in COVID-19. One-Sentence SummarySARS-CoV-2 spike induces structurally abnormal blood clots and thromboinflammation neutralized by a fibrin-targeting antibody.
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