Irish team begin COVID drug therapy trial

May benefit those who are critically ill
  • Deborah Condon

Irish scientists have begun a clinical trial for a drug therapy that could be beneficial for people who are critically ill in intensive care with COVID-19.

A team from the Royal College of Surgeons in Ireland (RCSI) has begun a controlled clinical trial involving alpha-1-antitrypsin. This is a naturally occurring human protein that is produced by the liver and released into the bloodstream. It normally acts to protect the lungs from the destructive actions of common illnesses.

The RCSI trial is looking at the protein in relation to critically ill patients who are being mechanically ventilated in ICU with COVID-19-associated Acute Respiratory Distress Syndrome.

"As of late June, more than 9.5 million laboratory-confirmed cases of COVID-19 have been documented globally, with over 490,000 deaths. These numbers continue to grow substantially. In Beaumont Hospital, we have had over 500 patients admitted to the hospital, and nearly 50 patients requiring admission to intensive care," commented RCSI professor of medicine, Prof Gerry McElvaney.

He explained that 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," he noted.

According to Prof Ger Curley, RCSI professor of anaesthesia and critical care, and a consultant in anaesthesia and intensive care in Beaumont Hospital, it is already known 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".

In a collaboration between the departments of medicine and critical care and anaesthesia, a team of scientists led by Prof McElvaney and Prof Curley sought to determine the type of inflammation affecting the COVID-19 patient in ICU, and to ascertain whether there was a relationship between this type of inflammation and the need for intubation and mechanical ventilation.

Their study found that a number of highly inflamed proteins were all increased in infected patients compared to healthy controls. There was also a difference in the profiles of patients in ICU and those who were infected but stable.

However, the most unanticipated differentiating factor between patients with stable and severe disease was not the degree of increase in inflammatory proteins, but rather the relative decrease in levels of an anti-inflammatory protein, which indicates that the patients' anti-inflammatory mechanisms were failing.

"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," Prof Curley explained.

He said that the scientists are confident that this clinical trial will demonstrate the potential for alpha-1 "to improve the outcomes for patients with the most severe COVID-19-induced respiratory difficulties".

The clinical trial is being sponsored by the RCSI University of Medicine and Health Sciences and is coordinated by the the RCSI Clinical Research Centre. Beaumont Hospital is the first site to recruit patients and other sites in Ireland will also participate.

Details of the trial have been published in the American Journal of Respiratory and Critical Care Medicine.


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