Researchers Identify Immune and Blood Vessel Damage as Core Drivers of Long COVID
Nikhil Prasad Fact checked by:Thailand Medical News Team Oct 17, 2025 3 weeks, 2 days, 21 hours, 58 minutes ago
Medical News: A team of scientists from the Instituto de Salud Carlos III in Madrid, Spain, along with collaborators from the Universidad Nacional de Educación a Distancia, Hospital Clínico San Carlos, and the IrsiCaixa AIDS Research Institute, has uncovered how immune system malfunctions and blood vessel damage combine to cause dangerous clotting problems in people suffering from Long COVID. Their findings reveal that even more than two years after infection, the immune and vascular systems of some patients remain abnormal.
Researchers Identify Immune and Blood Vessel Damage as Core Drivers of Long COVID
The study analyzed 32 people with Long COVID—those with symptoms lasting over 12 weeks after infection—and compared them with 35 individuals who had fully recovered. The researchers looked for signs of immune imbalance, blood vessel damage, and clotting problems. Blood and stool samples were carefully examined for viral traces and inflammatory markers. This
Medical News report highlights that no active virus was detected, but clear signs of ongoing body-wide disturbances were found.
Persistent Immune Confusion and Endothelial Damage
Even after 26 months, Long COVID patients showed higher blood levels of clotting factors like prothrombin, thrombin, and fibrinogen, which indicate that their blood vessels remained inflamed or injured. The scientists also found increased levels of CRP—a marker of inflammation—and a protein called sEPCR, which weakens the body’s natural ability to prevent excessive clotting. Together, these findings point to continuing endothelial dysfunction, meaning the inner lining of blood vessels remains damaged and promotes clot formation.
At the same time, levels of REG3A, a key molecule that helps protect and repair the gut’s lining, were lower than normal in Long COVID patients. This could mean that chronic gut inflammation or barrier leaks allow bacteria or toxins to spread into the bloodstream, fueling immune overactivation. Patients also had weaker antibody responses and reduced ability to neutralize the virus, suggesting that their immune systems were exhausted or poorly coordinated.
Vaccination Patterns and Reinfection Links
Interestingly, the study discovered that people who received mixed types of COVID-19 vaccines were more likely to develop Long COVID compared to those who received consistent vaccination types. This suggests that inconsistent vaccine combinations may weaken long-term immunity. Additionally, Long COVID patients had more breakthrough infections than recovered individuals, indicating that repeated infections could worsen or prolong the condition.
Blood Clotting and Inflammation as Central Mechanisms
Markers of blood clotting and inflammation appear to reinforce each other in a dangerous cycle. Persistent activation of thrombin and CRP increases the risk of clot formation, which in turn may damage small blood vessels and cause microclots that block oxygen flow to tissues. This
could explain many Long COVID symptoms such as fatigue, brain fog, and heart palpitations. The researchers also used an artificial intelligence model that accurately distinguished Long COVID patients from healthy ones, highlighting the potential for new diagnostic tools.
Conclusion
The study shows that Long COVID is not simply lingering fatigue or anxiety—it is a complex, biologically measurable disorder involving long-term immune misfiring, vascular injury, and blood clot abnormalities. The researchers emphasize that uniform vaccination schedules and ongoing medical monitoring of inflammation and clotting markers are critical to prevent chronic complications. The findings also strengthen the idea that Long COVID is driven by continuous inflammation rather than immune deficiency, offering new directions for treatment and prevention strategies.
The study findings were published in the peer-reviewed journal: Frontiers in Immunology.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1613195/full
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Read Also:
https://www.thailandmedical.news/articles/long-covid
https://www.thailandmedical.news/articles/coronavirus
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