Abnormal immune responses are thought to be the main driver of severe COVID-19. A protein circulating in the blood called soluble urokinase plasminogen activator receptor (suPAR) is known to be derived from immune cells. Right now, it has been shown to play an important role in the complications of COVID-19.
A research team from around the world — including Dr. Salim Hayek, medical director of the Frankel Cardiovascular Center Clinic at the University of Michigan, and Dr. Shengyuan Luo, an internal medicine resident at Rush University Medical Center — has been studying suPAR and its association with COVID-19 cases. relationship to the key results.
Higher suPAR levels were associated with an increased risk of blood clot formation, the researchers noted in a multinational observational study of hospitalized patients with COVID-19. In addition, they noted that suPAR levels in hospitalized COVID patients were associated with venous thromboembolism, including pulmonary embolism, but not with a marker of clot formation called D-dimer.
“Traditionally, clinicians have used D-dimer, a product of blood clot breakdown, to assess VTE activity,” Luo said, “However, this marker has proven to be less predictive in COVID-19 , because clot formation is largely caused by a uniquely abnormal immune response to the virus.”
The researchers therefore envision that combining immune system markers suPAR and D-dimer could improve the reliability of determining who is at high or low risk of clot formation among COVID hospitalized patients.
“Even before the pandemic, before COVID-19, we had this idea of suPAR,” Hayek said, “and we saw levels of suPAR markers that were strongest in other viral infections and adverse outcomes in heart and kidney disease. risk factors.”
When scientists discovered the severity of thrombosis in COVID-19 patients early in the pandemic, they turned to suPAR for more observations. Early studies have shown that suPAR levels are three to five higher in COVID-19 patients and are often associated with disease complications.
“We have previously shown that patients with high suPAR levels have a much higher risk of death, kidney damage, respiratory failure requiring mechanical ventilation, and now venous thromboembolism,” Hayek said.
For the study, scientists compiled data from 1,960 adults hospitalized with COVID-19 who had their suPAR levels measured at the time of admission. All patients are monitored until they are discharged, or in some cases, until death.
Important attributes of the patients in this study included: age, gender, ethnicity, and body mass index. Other medical conditions evaluated at admission include: diabetes, congestive heart failure, high blood pressure, stroke, and other important cardiac and inflammatory conditions.
The researchers measured D-dimer and suPAR levels and diagnosed VTE (deep vein thrombosis and pulmonary embolism) by lower extremity ultrasound and lung scans during the 30-day period during the patient’s hospital stay.
The results showed that 163 patients developed VTE, of which 65 patients developed deep vein thrombosis, 88 patients developed pulmonary embolism, and 10 patients developed both conditions. Patients with blood clots had nearly 50% higher suPAR levels than those without blood clots. And when suPAR levels bound to D-dimer, the researchers could classify 41 percent of study participants as being at low risk of developing VTE.
“There is a modest positive correlation between suPAR and D-dimer levels; they all tend to go in the same direction,” Hayek explained.
Now that there is a link between suPAR levels and blood clot formation, clinicians can assess who is at high or low risk, which will help them decide what therapy to treat them with. Like high-risk people can be treated with anticoagulant medication before a blood clot forms.
Studying suPAR and its link to the immune system has positive implications for key COVID-19 patients and beyond.
“On the background side, there’s been a lot of work showing that this molecule (suPAR) has bad effects on the body at higher levels. Companies are developing drugs that target suPAR, so we might be measuring this regularly,” Hayek said.
The current study is ongoing to test anti-suPAR therapy in COVID-19 patients.
“Over the next year or so, we’re likely to have an impact on critical care for several other populations that goes beyond COVID,” Hayek said.