Just a few weeks ago, the World Health Organization declared the global corona emergency over. But millions of people around the world are still suffering from the effects of COVID-19, many of them for months or years. "Long COVID is a new disease that affects many people. We still lack knowledge about how it develops and how to treat it," says Leo Nicolai, M.D., a researcher and physician at the Medical Clinic and Polyclinic I of the LMU University Hospital Munich. He and two other colleagues analyzed data from existing studies to further investigate the link between Long COVID and thromboinflammation.
Thromboinflammation is a pathological process in which the normal mechanisms of blood clotting and inflammation get out of control. The immune system and the coagulation cascade are activated and reinforce each other, increasing the tendency to clot.
Damaged vessel wall cells indicate thromboinflammation
The publication focused on two questions: first, does thromboinflammation have a potential impact on Long COVID; second, does it provide promising therapeutic approaches? The team found evidence that components of thromboinflammation are altered in some patients with Long COVID. Thus, dysfunctions of the vascular system can be observed: An increase in the corresponding markers in the blood indicates that the endothelial cells (cells of the vessel wall) are damaged in some Long COVID patients.
"There is little data on the coagulation system itself, but it looks as if the dissolution of thrombi is reduced, i.e. it functions worse," reports Dr Leo Nicolai. Neutrophils (specialized immune cells) are more activated in some Long COVID patients, as are platelets, which play a central role in blood clotting and immune processes. In addition, both types of cells bind more strongly to each other. This can also contribute to increased thromboinflammation.
Increased risk of thrombosis
The analysis shows that increased thromboinflammation in patients with Long COVID also leads to increased thrombosis. This affects both small and large vessels and can lead to stroke, heart attack or pulmonary embolism. The risk of microvascular thrombosis can be detected by a marker in the blood, a degradation product of fibrin. Fibrin is the "glue" that holds blood clots together in the vessels. This degradation product remains elevated in 20 percent of patients after Covid-19 has worn off. The risk of large vessel thrombosis also increases - by 1.8 times for venous thrombosis and 1.3 times for arterial thrombosis.
So how does thromboinflammation develop in Long COVID? The team discusses three hypotheses in the study. First, during acute covid disease, damage to the vasculature may not be completely resolved. Second, in some patients, SARS-CoV-2 genetic material could be detected in various organs, such as the intestine. This could mean that the virus remains in the body after the acute infection and triggers recurrent reactions, which can also lead to thromboinflammation. "However, only the RNA of the virus can be detected; whether it is also functional is unknown," points out Dr Leo Nicolai. A third hypothesis for the development of thromboinflammation is that infection with SARS-CoV-2 triggers a dysregulated immune response that does not rebound and damages the body.
Studies of anticoagulants and antivirals should provide clarity
How can thromboinflammation and thrombosis be prevented? There is too little data to answer this question satisfactorily. Anticoagulants are not yet recommended, but a study is investigating whether their use could have a positive effect. It is also being investigated whether antiviral drugs that are already available can prevent thromboinflammation. Vaccination against SARS-CoV-2 may also be helpful, but there is not enough data yet.
The researchers conclude that thromboinflammation may play a role in the development of the disease, at least in a subgroup of patients with Long COVID. However, too little is known about cause and effect. Nor is it known how many patients will ultimately be affected. For example, the link between exposure to thromboinflammation and actual disease is lacking, as is knowledge about what treatment makes a difference. "Thromboinflammation is a very heterogeneous and complex disease. There are still too few large-scale studies and therefore too little data to be able to assess the situation with certainty," says Dr Leo Nicolai. Extensive studies on the efficacy of anticoagulants and antiviral drugs that are already underway should shed more light.
Publication: Thrombo-inflammation in Long COVID – the elusive key to post-infection sequelae? Leo Nicolai, Rainer Kaiser, Konstantin Stark. jth journal of thrombosis and haemostasis (May 2023). DOI: https://doi.org/10.1016/j.jtha.2023.04.039
Scientifc contact: Dr Leo Nicolai, Medical Clinic I, LMU University Hospital Munich, leo.nicolai(at)med.uni-muenchen.de
Contact: Christine Vollgraf, Press and Public Relations, German Center for Cardiovascular Research (DZHK), +49 30 3465 529 02, presse(at)dzhk.de