Identifying Potential Therapeutic Targets for COVID-19

Scientists have identified a unique pattern of 6 molecules that could be used as therapeutic targets to treat coronavirus 2019 (COVID-19).

Douglas Fraser, lead researcher, Lawson and Western's Schulich School of Medicine & Dentistry and Critical Care Physician at London Health Sciences Centre (LHSC), headed up a team of investigators who reported their findings in Critical Care Explorations.

The team is the first in the world to profile the body's immune response to COVID-19. After looking at 57 inflammatory molecules, they found six molecules that were uniquely elevated in COVID-19 intensive care unit (ICU) patients. They include tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2.

"Clinicians have been trying to address this hyperinflammation but without evidence of what to target," Fraser said. "Our study takes away the guessing by identifying potential therapeutic targets for the first time."

According to some reports, patients’ immune systems can overreact to COVID-19 and cause a cytokine storm, which elevates levels of inflammatory molecules that damage healthy cells.

This study was conducted at LHSC in Ontario, Canada and included 30 participants. Of the participants, 10 had COVID-19, 10 patients had other infections that required them to be treated in the ICU, and 10 were healthy.

According to the investigators, the ICU patients who did not have COVID-19 had significantly higher unilateral pneumonia, but the COVID-19 ICU patients were more likely to have bilateral pneumonia. Sepsis was identified in 20% of the non-COVID-19 patients, and only suspected in the remaining 80%. All other reported baseline measures were nonsignificant between patients. However, a 40% mortality rate was determined for the COVID-19 patients.

They collected daily blood samples starting at admission and up to 3 days in COVID-19 negative patients, or up to 7 days in COVID-19 positive patients. The samples were processed in a lab and then analyzed using statistical methods and artificial intelligence (AI).

The investigators found that inflammation profiling was able to predict the presence of COVID-19 in critically ill patients with 98% accuracy. They also found that one of the molecules (heat shock protein 70) was strongly associated with an increased risk of death when measured in the blood early during the illness.

The investigators also mentioned a few challenges. They only studied critically ill patients and they could not determine the inflammatory changes contributing to ICU admissions. In addition, the number of overall patients and the number of COVID-19 patients was limited.

The team views this as the first step in trying to find potential COVID-19 therapies.

"Understanding the immune response is paramount to finding the best treatments," Fraser stated. "Our next step is to test drugs that block the harmful effects of several of these molecules while still allowing the immune system to fight the virus."