A team of scientists from the US has discovered that the spike glycoprotein of Covid-19 can induce the formation of highly inflammatory blood clots amenable to neutralization by a fibrin-targeting monoclonal antibody,
This will pave the way for a completely new method to reduce thrombotic inflammation from Covid.
Clotting is a major issue with Covid and even young patients with milder symptoms can be affected by pulmonary embolism, stroke, and sudden death. So this team tried to find the mechanism of blood clot formation.
Their studies have shown that the Spike glycoprotein from the virus can bind to the blood coagulation factor fibrinogen and induce structurally abnormal, rougher, and more dense blood clots with better proinflammatory activity. Fibrin polymerization was also increased, as evidenced by the incubation of spike glycoprotein with healthy donor plasma.
Furthermore, Covid viral particles enhanced the activation of fibrin-mediated microglia and induced fibrinogen-dependent lung pathology. On the other hand, when a novel monoclonal antibody 5B8 was used, thrombotic inflammation was strongly inhibited. 5B8 is a special monoclonal antibody generated against a specific fibrin epitope.
So this study reveals that coagulopathy is not a mere consequence of inflammation. Essentially, the interaction of Covid spike glycoprotein with fibrinogen and fibrin can give rise to abnormal blood clot formation, driving, in turn, inflammatory processes.
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 Summary SARS-CoV-2 spike induces structurally abnormal blood clots and thromboinflammation neutralized by a fibrin-targeting antibody.
This will pave the way for a completely new method to reduce thrombotic inflammation from Covid.
Clotting is a major issue with Covid and even young patients with milder symptoms can be affected by pulmonary embolism, stroke, and sudden death. So this team tried to find the mechanism of blood clot formation.
Their studies have shown that the Spike glycoprotein from the virus can bind to the blood coagulation factor fibrinogen and induce structurally abnormal, rougher, and more dense blood clots with better proinflammatory activity. Fibrin polymerization was also increased, as evidenced by the incubation of spike glycoprotein with healthy donor plasma.
Furthermore, Covid viral particles enhanced the activation of fibrin-mediated microglia and induced fibrinogen-dependent lung pathology. On the other hand, when a novel monoclonal antibody 5B8 was used, thrombotic inflammation was strongly inhibited. 5B8 is a special monoclonal antibody generated against a specific fibrin epitope.
So this study reveals that coagulopathy is not a mere consequence of inflammation. Essentially, the interaction of Covid spike glycoprotein with fibrinogen and fibrin can give rise to abnormal blood clot formation, driving, in turn, inflammatory processes.
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 Summary SARS-CoV-2 spike induces structurally abnormal blood clots and thromboinflammation neutralized by a fibrin-targeting antibody.
