A new COVID study uncovers a new link between the immune system and blood clots, which could help with the treatment of critical conditions.
Blood clots may occur in as many as one-third of COVID-19 hospitalized patients. Blood clots that go to the lungs, such as pulmonary embolisms, can often be fatal. In fact, these clots caused death in almost a third of COVID-19 patients.
The main cause of severe COVID-19 is assumed to be an aberrant immunological response. One protein, known as soluble urokinase plasminogen activator receptor, or suPAR, is found in the blood and comes from immune cells. It has been demonstrated that suPAR plays a significant role in COVID-19 symptoms.
Shengyuan Luo, M.D., an internal medicine resident at Rush University Medical Center, Salim Hayek, M.D., the medical director of the University of Michigan Frankel Cardiovascular Center Clinics, and a group of researchers from all over the world have been researching suPAR and its connection to crucial outcomes in COVID-19 cases.
Researchers discovered that greater suPAR levels were associated with an increased risk of blood clot formation in a study published by the International Study of Inflammation in COVID-19, a multinational observational study of patients hospitalized for COVID-19.
In contrast to D-dimer, a blood clot formation marker, their new research, which was published in the Journal of the American Heart Association, suggests that suPAR levels in hospitalized COVID patients were related to venous thromboembolism, including pulmonary embolism.
D-dimer, a substance that breaks down blood clots, is traditionally used by clinicians to evaluate VTE activity, according to Luo. The blood clot formation in COVID-19, however, has shown to be less predictable due to a particularly aberrant immune response to the virus.
Therefore, the authors hypothesized that combining suPAR, an immunological marker, with D-dimer could improve the accuracy of identifying hospitalized COVID patients at high or low risk for blood clot formation.
“Even before the pandemic, before COVID-19, we had this idea about suPAR,” says Hayek, adding “We were seeing levels of the suPAR marker as the strongest risk factor for bad outcomes in other viral infections and in heart and kidney disease.”
Early in the pandemic, when researchers noticed how serious blood clot formation was in COVID-19 patients, they went to suPAR for additional information. Previous research revealed that suPAR levels were three to five times higher and frequently linked to illness problems in COVID-19 patients.
According to prior research, people with high suPAR levels are substantially more likely to die, suffer kidney damage, experience respiratory failure requiring mechanical ventilation, and now develop venous thromboembolism.
Study results
Researchers gathered information from 1,960 patients who were hospitalized with COVID-19 and whose suPAR levels were assessed at the time of hospital admission for the study. Every patient was watched over until they were either released or, in certain situations, until they passed away.
Age, sex, race, and body mass index were significant patient characteristics. Diabetes, hypertension, congestive heart failure, stroke, and other serious inflammatory and cardiologic illnesses were also evaluated at the time of admission.
During the 30-day hospital stays of the patients, researchers evaluated D-dimer and suPAR levels and identified VTE (deep vein thrombosis and pulmonary embolism) using scans of the lungs and ultrasounds of the lower limbs.
According to the findings, there were 163 patients who experienced VTE, and of those, 65 experienced deep vein thrombosis, 88 experienced a pulmonary embolism, and 10 experienced both. SuPAR levels were nearly 50% greater in patients who experienced blood clots compared to those who did not. Additionally, when suPAR levels and D-dimer were combined, researchers could categorize 41% of study participants as having a low risk of developing VTE.
According to Hayek, there is a slight positive association between suPAR and D-dimer levels; they both frequently trend in the same direction.
Since suPAR levels and blood clot formation have been linked, clinicians can now determine who is at high or low risk, which will help them choose the best medicines to employ to treat patients. For instance, medicine could be given to a high-risk patient before a blood clot forms.
Studying suPAR and its relationship to the immune system provides benefits for critically ill COVID-19 patients as well as for others.
“In the background, there’s been a lot of work showing that this molecule (suPAR) is doing something bad to the body when levels are high,” Hayek adds. “Companies are developing drugs to target suPAR, and so we might be measuring this on a regular basis.”
Hayek is optimistic about what the Michigan Medicine COVID-19 Cohort and the International Study of Inflammation in COVID-19 have been able to do since the start of the pandemic in terms of preventing serious outcomes in COVID-19 and other infectious diseases.
Anti-suPAR treatments are currently being studied in COVID-19 patients.
According to Hayek, “in the next year or so, we might be able to impact critical care in several other populations with implications that go beyond COVID.”
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