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.

doi:10.1101/2021.10.12.464152

bioRxiv · 10.1101/2021.10.12.464152

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.

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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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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.. 2021-10-13. SARS-CoV-2 spike protein induces abnormal inflammatory blood clots neutralized by fibrin immunotherapy. https://doi.org/10.1101/2021.10.12.464152

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