Researchers from at RCSI University of Medicine and Health Sciences have started a clinical trial for a COVID-19 disease therapy for the sickest patients. The team, led by RCSI Professors Gerry McElvaney and Ger Curley, published a paper in the American Journal of Respiratory and Critical Care Medicine describing how the body’s normal inflammatory response is different in COVID-19 patients.
The researchers are testing the ability of alpha-1-antitrypsin to work as a therapy for COVID-19 patients who are on ventilators because of Acute Respiratory Distress Syndrome (ARDS). Alpha-1-antitrypsin is a protein produced by the liver that normally helps to prevent illness in the lungs.
Says McElvaney: "The current management of severe COVID-19 remains supportive, focusing on supplemental oxygen and ventilator support in the event of acute respiratory failure. Despite the implications for global health, the inflammatory characteristics of patients with COVID-19 are not yet fully understood. A greater understanding of how the body's inflammatory mechanisms are impacted upon by COVID-19 could open the door to several potential therapies including antiviral medications and targeted immune-modulators such as alpha-1-antitrypsin."
Curley adds, “We know from in-hospital studies that many COVID-19 patients in ICU develop severe inflammation throughout the body with a disproportionately high rate of progression to acute respiratory distress syndrome, acute renal failure, shock and heart arrhythmia."
The team set out to figure out the type of inflammation found in COVID-19 patients and determine if there was a relationship between the need for ventilation and the type of inflammation. What they discovered that all infected patients had highly inflamed proteins, but they also found that the difference between stable patients and those in the ICU was the decrease in anti-inflammatory proteins, meaning the anti-inflammatory mechanisms were no longer working.
"This finding suggests to us that a therapy which augments the body's own inflammation resolving mechanisms might have a positive impact. Alpha-1 protects the airway from damage during acute pulmonary infection. It is also a potent anti-inflammatory and acts to protect the immune system. Of particular relevance to COVID-19, it has been shown to modulate the production and activity of several key pro-inflammatory proteins", explained Prof. Curley.