Alarming Immune and Clotting Protein Imbalances Discovered in Post COVID Vaccine and Infection Syndrome
Nikhil Prasad Fact checked by:Thailand Medical News Team May 06, 2025 2 weeks, 3 days, 22 hours, 43 minutes ago
Medical News:
New Study Uncovers Elevated Levels of Serum Amyloid A1 A2 Attractin and Clotting Factors X and XI in Affected Patients
A groundbreaking new study led by scientists from Stellenbosch University in South Africa and the University of Liverpool in the United Kingdom has shed new light on the molecular abnormalities driving the mysterious and debilitating symptoms seen in people suffering from Post COVID Vaccine and Infection Syndrome (PV/PIS). This condition, often marked by long-lasting fatigue, cardiovascular issues, neurological problems, and blood clotting disorders, can occur after either COVID-19 infection, vaccination, or both.
Alarming Immune and Clotting Protein Imbalances Discovered in Post COVID Vaccine and Infection Syndrome
The research team, which includes experts such as Maxine Waters, Mare Vlok, Elouise Kroon, Maritha Kotze, and Professor Etheresia Pretorius, performed a highly detailed proteomics analysis on blood samples from affected individuals. Their findings reveal a consistent pattern of immune system dysregulation and abnormal clotting activity. In this
Medical News report, scientists identified a significant increase in the blood levels of acute inflammatory proteins serum amyloid A1 (SAA1) and serum amyloid A2 (SAA2), as well as the immune-modulating protein attractin and clotting factors X and XI.
Understanding Post Vaccine and Infection Syndrome
PV/PIS is a relatively new term coined by researchers to describe a group of patients who develop persistent symptoms following COVID-19 vaccination and/or infection. These individuals often experience symptoms that resemble those of Long COVID, such as brain fog, chronic fatigue, chest pain, and joint aches, but without clear evidence to distinguish whether these issues stem from the infection or the vaccine—or both. This overlap has made diagnosis and treatment difficult.
In the current study, 30 participants were recruited and divided into two groups: 16 healthy controls and 14 PV/PIS patients. All PV/PIS participants had received the Pfizer-BioNTech vaccine and later developed prolonged symptoms, some after a documented COVID-19 infection. Importantly, all individuals were tested using advanced mass spectrometry tools to determine the exact proteins circulating in their blood plasma.
Elevated Inflammatory and Clotting Proteins Detected
What stood out in the research was a marked increase in certain proteins associated with inflammation and clotting. Both SAA1 and SAA2 were found to be significantly elevated—by 1.72 and 1.66 times respectively. These proteins are known markers of inflammation and are typically produced in large quantities during acute immune responses. High levels of these proteins have previously been linked to chronic diseases and conditions involving abnormal protein clumping known as amyloidosis.
Attractin, another protein involved in immune signaling and the migration of immune cells, was upregulated by a striking 2.57 times in PV/PI
S patients. Researchers believe this protein may play a role in promoting a dangerous immune imbalance known as the Th17 response, which has been linked to autoimmunity and excessive inflammation.
Equally concerning were the significantly elevated levels of clotting factors X and XI—up by 2.06 and 1.63 times respectively. These clotting proteins are essential in forming blood clots, and their overactivity may contribute to the formation of the tiny, resistant microclots that have now been associated with both Long COVID and vaccine-related complications. These microclots can block small blood vessels and lead to oxygen shortages and organ dysfunction.
Amyloid Risk and Protein Misfolding
To better understand the risks posed by these elevated proteins, the researchers used a tool called AmyloGram to predict their potential to form harmful amyloid structures. Both SAA1 and SAA2 scored high, suggesting they have a tendency to misfold and form insoluble fibrils that can damage tissues. Attractin, too, showed a very high amyloid score, raising concern that it may also contribute to the build-up of these dangerous protein clumps, especially when cross-linked with fibrinogen—a protein central to blood clotting.
The findings suggest that these misfolded proteins may not only play a role in ongoing inflammation but also in the abnormal clotting observed in PV/PIS patients. In turn, this can drive a vicious cycle of immune activation and blood vessel damage.
A Distinct Condition from Long COVID
Interestingly, when compared to previous studies on Long COVID, the researchers found that the PV/PIS protein profile was distinctly different. While both conditions show signs of immune activation and coagulopathy, the proteins involved and their levels varied, indicating that PV/PIS may be a separate clinical entity, despite some overlapping symptoms.
For instance, while Long COVID patients often showed upregulation of inter-alpha trypsin inhibitors ITIH1 and ITIH2, the PV/PIS group showed increases in ITIH3 and ITIH4 instead. These subtle yet important differences could help clinicians better diagnose and eventually treat patients suffering from these chronic post-COVID complications.
Conclusion
This study provides strong evidence that PV/PIS is driven by persistent immune system abnormalities and clotting dysfunction, even in patients who experienced only mild initial symptoms or had no clear COVID-19 infection history. The significantly elevated levels of inflammatory and amyloid-prone proteins like SAA1, SAA2, attractin, and clotting factors X and XI suggest that this condition is not only real but also potentially dangerous if left untreated. These molecular markers may eventually help doctors develop specific diagnostic tests and targeted therapies. However, much more research is needed to understand the full implications of these findings and to determine why some individuals are more susceptible to PV/PIS than others.
The study findings were published on a preprint server and is currently being peer reviewed.
https://www.researchsquare.com/article/rs-6521005/v1
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