A recent study published in Nature by Gladstone Institutes and collaborators has revealed that the blood coagulation protein fibrin is responsible for the unusual clotting and inflammation that are common symptoms of COVID-19. The study also found that fibrin suppresses the body’s ability to clear the virus, as well as identified a new antibody therapy to combat these effects. Contrary to previous beliefs that blood clotting in COVID-19 was a consequence of inflammation, the study shows that blood clotting is a primary effect, driving other problems such as toxic inflammation, impaired viral clearance, and neurological symptoms.
By conducting experiments in the lab and with mice, researchers showed that fibrin, a protein in the blood that normally enables healthy blood coagulation, becomes toxic in COVID-19. This toxicity occurs as fibrin binds to both the virus and immune cells, leading to the formation of abnormal clots that result in inflammation, fibrosis, and loss of neurons. Neutralizing blood toxicity with fibrin antibody therapy in mice was shown to protect the brain and body after COVID infection, suggesting a potential new treatment approach for the disease.
The study challenges the prevailing theory that inflammation is the primary driver of blood clotting in COVID-19. While many scientists hypothesized that inflammation from the immune system’s rapid response to the virus caused blood clotting, the new findings suggest that blood clots play a principal role in COVID-19 and may have evolved to support the virus’s own benefit. Through experiments in mice, researchers demonstrated that the virus spike protein directly binds to fibrin, leading to structurally abnormal blood clots with enhanced inflammatory activity.
The study also revealed that fibrin suppresses the body’s “natural killer” cells, which are responsible for clearing the virus from the body. When fibrin was depleted in mice, the natural killer cells were able to effectively clear the virus. The findings suggest that fibrin is necessary for the virus to cause harm in the body, highlighting the potential of targeting fibrin as a therapeutic strategy for COVID-19.
The study’s results have significant clinical implications, particularly for patients with long COVID, who experience a range of persistent symptoms. The researchers identified a potential therapy that targets fibrin’s inflammatory properties without affecting blood coagulation, showing promise in reducing severe symptoms in infected mice. A humanized version of the therapy is currently in Phase 1 safety and tolerability trials, with the potential to be used in advanced trials for COVID-19 and long COVID patients.
Overall, the study underscores the importance of collaborative, multidisciplinary research in addressing complex medical problems such as blood clotting in COVID-19. By bringing together experts from immunology, hematology, virology, neuroscience, and drug discovery, the study sheds light on the mechanism of fibrin in COVID-19 and offers a path forward for treating patients with severe symptoms. The findings not only provide new insights into the disease but also offer a novel strategy for addressing the long-term effects of COVID-19 and long COVID on patients’ cognitive function and overall health.